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Microplastics

Microplastics Cause Cognitive Deficits in APOE4 Mice

Scientists have demonstrated that short-term exposure to microplastics causes Alzheimer’s-like effects in mice expressing human APOE4 versus APOE3. These effects were sex-dependent, mirroring the disease in humans [1].

Microplastics and the brain

Exposure to tiny particles that plastic products shed (microplastics) has been linked to increased mortality and diseases [2]. Microplastics are ubiquitous and enter organs, including the brain, triggering inflammation. A recent study showed alarming levels of microplastic accumulation in human brains [3]. However, rigorous studies of the exact effects of microplastics on the brain have been scarce.

A new study by researchers at the University of Rhode Island College of Pharmacy asked a question whether microplastics exposure can promote Alzheimer’s disease in mice genetically predisposed to it. The team created genetically modified mice that were homozygous for either the human APOE ε3 or APOE ε4 allele. The latter is strongly associated with an increased risk of Alzheimer’s, while the former is considered “normal,” neither increasing risk nor providing protection. Both sexes were included to avoid missing sex-specific effects.

At 3-6 months of age, before developing pathologies, mice were randomized into control or exposure groups, with 8 animals per each combination of sex, genotype, and condition. Then, for three weeks, the treatment groups drank water containing a mix of fluorescent polystyrene particles at two sizes: 0.1 μm (nanoplastic) and 2 μm (microplastic), at 0.125 mg/mL. The chosen dose was intentionally high relative to what the average human receives from the environment. This was done to compensate for the short duration of exposure.

“In these mice, like in people, it’s not a guarantee that you’re going to see any changes in cognition. You could have identical twins both carrying APOE4, one totally cognitively healthy, and the other could develop Alzheimer’s disease,” said URI pharmacy assistant professor Jaime Ross, the lead author of the study.

Males more apathetic, females more forgetful

The team then ran a battery of cognitive tests. In the open field test, cognitively normal mice are expected to spend little time in the open, which is these rodents’ natural behavior helping them to avoid predators. Male APOE ε4 mice who were exposed to microplastics, however, spent much more time in the center of the arena, a pattern that the authors interpret as apathy-like cognitive disruption.

Females did not show this pattern. However, in a different test, novel object recognition (NOR), it was the female APOE ε4 mice who showed poorer recognition memory. Several other tests produced null results, but the authors suggest it actually shows that, just like in human Alzheimer’s, the effect was less “broad anxiety” and more cognition-focused.

Ross tied the findings to known sex-related differences in Alzheimer’s symptoms in humans. “In human Alzheimer’s patients,” she said, “men tend to experience more changes in apathy; they care less. Women experience more changes in memory. So, the memory and the apathy connection are pretty clear: when you expose animals that are carrying the largest known risk factor in humans for developing Alzheimer’s disease to micro- and nanoplastics, lo and behold, their behavior changes in a sex-dependent manner similar to the sex-dependent differences we see with Alzheimer’s patients.”

Time spent in center by allele and exposure

“Similar to what we’re seeing in the real world”

The plastic particles were confirmed to reach the brain, at least the larger ones (0.1 μm particles are below histology detection limits), and the researchers attempted to analyze possible mechanisms behind the impact on cognition. The team examined GFAP, a marker of astrocyte activation/health, and IBA1, a microglial marker, but the results were inconclusive. The researchers suggest that microplastics exert their effect on cognition not via classical microglial inflammation and call for further research.

Two important caveats apply. First, the high dose and short exposure limits the study’s generalizability. Second, real-world plastics are weathered, chemically varied, and often carry adsorbed pollutants. This study used pristine polystyrene spheres, which do not mirror these conditions.

“So, that tells us there’s something about lifestyle, something about the environment going on,” Ross said. “There are modifiable factors we’re studying related to Alzheimer’s – diet, exercise, vitamins, and especially environmental toxins like microplastics. If you carry the APOE4, and you happen to consume a lot of microplastics, will this contribute to Alzheimer’s disease?”

“There has not been a lot of money spent on the human health impacts of microplastics,” she added. “It’s interesting that what we’re seeing in mice is similar to what we’re seeing in the real world. We want to encourage further research into the scourge of micro- and nanoplastics.”

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Literature

[1] Gaspar, L., Bartman, S., Tobias-Wallingford, H., Coppotelli, G., & Ross, J. M. (2025). Short-term exposure to polystyrene microplastics alters cognition, immune, and metabolic markers in an apolipoprotein E (APOE) genotype and sex-dependent manner. Environmental Research Communications, 7(8), 085012.

[2] Marfella, R., Prattichizzo, F., Sardu, C., Fulgenzi, G., Graciotti, L., Spadoni, T., … & Paolisso, G. (2024). Microplastics and nanoplastics in atheromas and cardiovascular events. New England Journal of Medicine, 390(10), 900-910.

[3] Nihart, A. J., Garcia, M. A., El Hayek, E., Liu, R., Olewine, M., Kingston, J. D., … & Campen, M. J. (2025). Bioaccumulation of microplastics in decedent human brains. Nature medicine, 31(4), 1114-1119.

LongX Logo

LongX Hosts the Youth in Longevity Biotech Showcase

On September 18, 2025, Longevity Xplorer (LongX) will be hosting the first-ever “Youth in Longevity Biotech Showcase”, a virtual event featuring lightning talks from young professionals in longevity fellowships around the world. The event will cover fellow contributions and highlight the importance in supporting the next generation of leaders in aging biology. LongX welcomes the entire longevity community to attend.

Longevity Biotech Showcase

Registration link: https://luma.com/s6p9wenp

A range of prestigious aging and longevity-focused fellowships will be represented. This includes but is not limited to:

LongX – Xplore Program

A remote fellowship designed to help early career professionals apply themselves in the longevity biotech sector through courses, mentorship, and industry placements.

Lifespan Research Institute – Summer Scholars & Post-Baccalaurate Fellowship

A program for undergraduate students and recent graduates to conduct biomedical research on age-related diseases under the guidance of a scientific mentor, with an emphasis on developing both laboratory and communication skills.

Buck Postbaccalaureate Research Program

A 1-2 year program for recent college graduates to gain intensive research experience in aging and age-related diseases at the Buck Institute before pursuing an advanced degree or a career in the biotech industry.

TIME Initiative

An aging biology fellowship that serves as a talent accelerator, supporting ambitious future leaders with knowledge, community, mentorship, and project support.

This event serves to:

  • Promote cross-pollination between aging biology-focused fellowships
  • Improve transparency in program developments and outcomes
  • Increase support for aging biology training programs
  • Foster a networking space for those interested in talent and education in longevity

About LongX

LongX was launched in 2023 as a platform for youth interested in longevity. We prioritize fostering innovation and interdisciplinary collaboration, aiming for both short-term impact and long-term progress. We encourage exploration beyond traditional roles and aim to equip future experts with the skills to drive progress. Our Substack provides regular articles on our thoughts, experiences, and interviews.

Contact

Marvin Yan, Co-Founder

team@longx.bio

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future.
Old timepiece

Epigenetic Clocks Do Not Perfectly Capture Metabolic Health

In Aging Cell, researchers have published their surprising findings that epigenetic clocks are not significantly related to most measurements of metabolic health after weight loss interventions.

The utility of clocks

These researchers begin by discussing epigenetic clocks and how much the measured alterations in gene expression cause other aspects of aging, the details of which remain unclear [1]. Accelerated aging, as measured by these clocks, is associated with cardiometabolic diseases [2]; if altering the expression of clock-related genes is demonstrated to have benefits in this area, it could pave the way for interventions; if this method is demonstrated not to be beneficial, then they may remain useful simply as clocks. There is also the question of generalizability: whether or not clocks are equally valuable across populations.

Limited connections between clocks and metabolites

Here, the researchers focused on obese people by using data from the MACRO trial, which was conducted to test the effects of weight loss interventions between 2008 and 2011 [3].

This trial utilized 148 participants between 22 and 75 years of age who had high BMI indices (between 30 and 45) but did not have such metabolic diseases as cardiovascular disease or type 2 diabetes. They were divided into low-carbohydrate and low-fat groups; the low-carb group was reported to have more weight loss than the low-fat group. Adherence to these diets was high.

These researchers used three samples from each person: at baseline, 3 months, and 12 months. To minimize noise, two principal component-based clocks, PCPhenoAge and PCGrimAge, were used along with the DunedinPACE clock that natively measures age acceleration. Age, sex, ethnicity, body weight, education, smoking, and alcohol use were all factored in as covariates.

Interestingly, lower total cholesterol was found to be associated with more rapid aging, according to both PCPhenoAge and DunedinPACE. Other metabolic factors were found to be associated with accelerated aging, including reduced levels of ghrelin and adiponectin along with higher levels of insulin, the insulin resistance marker HOMA-IR, and C-reactive protein (CRP). PCGrimAge did not have any statistically significant association between metabolic factors and epigenetic aging.

After dietary interventions, however, most of these correlations disappeared; the only ones that remained were the low adiponectin and the high CRP according to the DunedinPACE clock.

The interventions themselves had noticeable effects. Only three months of dieting did not yield any statistically significant effect on epigenetic aging. However, after 12 months, despite the dets being more effective for weight loss, PCPhenoAge and PCGrimAge reported increased epigenetic aging in the low-carb group compared to the low-fat group. DunedinPACE, however, reported that epigenetic age acceleration was decreased in both groups.

As expected, the dietary interventions had significant benefits for metabolic issues. However, critical to this study, the reseachers found that none of these benefits were mediated by epigenetic alterations as measured by these clocks: “Specifically, all indirect effects and proportions mediated were non-significant (FDR > 0.05), suggesting that the observed associations were not driven through changes in epigenetic aging.”

A clock may not always reflect health

These results, or lack thereof, led the researchers to suggest that the health benefits of moderately rapid weight loss are not well-captured in epigenetic clocks designed to measure aging. Specifically, they note that there is an “uncoupling” between the metabolic benefits observed in these studies and clock measurements. They further suggest that this may be due to the time periods involved; DunedinPACE “may be more indicative of cumulative biological burden that changes gradually over time” and less sensitive to relatively short-term effects.

The researchers highlight that their study is in line with previous work on this topic; the CALERIE trial found that caloric restriction, a well-known longevity intervention, had some effects on DunedinPACE but fewer effects on PCPhenoAge and PCGrimAge [4]. In total, their findings led the researchers to specifically warn against the use of epigenetic clocks as surrogate endpoints in metabolism-related interventions, suggesting instead that they “should remain exploratory and be interpreted with more established physiological markers.”

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future.

Literature

[1] Ferrucci, L., Barzilai, N., Belsky, D. W., & Gladyshev, V. N. (2025). How to measure biological aging in humans. Nature Medicine, 1-1.

[2] Lo, Y. H., & Lin, W. Y. (2022). Cardiovascular health and four epigenetic clocks. Clinical Epigenetics, 14(1), 73.

[3] Bazzano, L. A., Hu, T., Reynolds, K., Yao, L., Bunol, C., Liu, Y., … & He, J. (2014). Effects of low-carbohydrate and low-fat diets: a randomized trial. Annals of internal medicine, 161(5), 309-318.

[4] Waziry, R., Ryan, C. P., Corcoran, D. L., Huffman, K. M., Kobor, M. S., Kothari, M., … & Belsky, D. W. (2023). Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial. Nature Aging, 3(3), 248-257.

Glucosamine

Regular Glucosamine Use Linked to Fewer Chronic Diseases

An analysis of UK Biobank data showed an association between regular glucosamine use and significantly lower risks of seven non-communicable chronic diseases [1].

A common supplement

Glucosamine, a sugar molecule with an amine group (amino sugar), is a supplement used by almost 20% of middle-aged adults in the U.S., U.K., and Australia [2]. It is recommended for osteoarthritis patients to reduce knee pain [3].

Glucosamine has also shown some broader beneficial effects, including on inflammatory responses [4], and it has been linked to reduced risks of cardiovascular disease, type 2 diabetes, lung cancer risks, and all-cause mortality [2,5-7]. However, comprehensive studies on the impact of glucosamine supplementation on non-communicable chronic diseases are lacking.

Given that non-communicable chronic diseases cause around three-quarters of all deaths worldwide and are responsible for a considerable economic burden, and taking into account the preliminary data on glucosamine’s biological mechanisms and positive effects, the researchers examined the impact of regular glucosamine supplementation and its association with the risk of developing major non-communicable chronic diseases.

Large cohort

The authors used a large dataset from the population-based UK Biobank. They only included participants who were free from non-communicable chronic diseases at the beginning of the study and had completed information on medicine use. They obtained the data of 269,033 participants. 52,556 (19.5%) were regular glucosamine users, making it the currently largest cohort with which to analyze this research question.

The participants provided the information regarding glucosamine use through self-reported questionnaires, which weren’t validated in any way. Since the questionnaire was constructed to give simple answers (‘yes’ or ‘no’), the researchers were unable to analyze more detailed information, such as dose-response, impact of duration, or frequency of treatment, or the impact of supplement forms, such as glucosamine sulfate, glucosamine hydrochloride, and N-acetyl-glucosamine.

When glucosamine users were compared to non-users, the researchers noted that “glucosamine users were older, more likely to be female, and had a lower level of socioeconomic deprivation.” They were also more likely to be current or former smokers, “tended to engage in excessive alcohol consumption, exhibit unhealthy dietary patterns, and participate in irregular physical activity.” To remove those differences between the glucosamine and control groups and make those two groups comparable, the researchers employed propensity score matching (PSM). Using this method, they compared 52,525 glucosamine users and 52,525 controls that had comparable characteristics. The data regarding those study populations included a median of almost 14 years of follow-up.

Lower risk of non-communicable chronic diseases

Data analysis, which included false discovery rate correction, showed an association between regular glucosamine use and significantly lower risks of seven non-communicable chronic diseases: esophageal cancer, gout, chronic obstructive pulmonary disease, colorectal cancer, chronic liver disease, heart failure, and coronary heart disease. These associations were robust and persisted when different statistical tools were applied to test their strength. There were also associations between the combination of glucosamine and chondroitin, another supplement often combined with glucosamine, to the risk of non-communicable chronic diseases.

Most of the associations were independent of age and gender. The exceptions involved heart failure, as regular glucosamine use was associated with a 22% lower risk of heart failure in men but not women; and irregular and rapid heart rhythms (atrial fibrillation), in which “regular glucosamine use was related to a 51% higher risk” in people younger than 65.

The authors cautioned that while they observed associations between glucosamine use and the risk of non-communicable chronic diseases, this study is observational and does not prove causal relationships.

However, they also derived a number called the population attributable fraction, which allowed them to quantify, at the population level, what proportion of disease risk may have been prevented by glucosamine use if the relationship is indeed causal. These numbers came out to 12.84% for esophageal cancer, 11.14% for gout, 6.53% for colorectal cancer, 5.67% for chronic obstructive pulmonary disease, 6.54% for chronic liver disease, 6.09% for heart failure, and 4.16% for coronary heart disease.

Many possible mechanisms

While the researchers didn’t experimentally investigate the mechanisms behind he observed association, they speculated on the possible biological processes behind it and discuss it in the light of published studies. For example, they discussed how the connection between glucosamine and reduced risk of cardiovascular diseases can be driven by its ability to help mitigate atherosclerotic lesion formation and its anti-inflammatory effects. The reduced risk of non-communicable chronic diseases can also be linked to glucosamine’s ability to mimic the metabolic effects of a low-carbohydrate diet, its antioxidant properties, or modulation of many cellular processes.

Like every study, this one also has some limitations. While the UK Biobank is a large dataset with many participants, and a plethora of information about each person, some information is not included, such as their reasons for taking glucosamine. If some of the participants took it because of joint discomfort or undiagnosed osteoarthritis, this would change their disease risk and impact the analysis, as participants who had non-communicable chronic diseases at the beginning of he study were excluded.

The results might also have limited generalizability, as the population in the UK Biobank is primarily of European ethnicity and has healthier habits than the general population. Additionally, the authors suspect that glucosamine users might be more conscious about health, introducing another bias. However, they tried to minimize the impact of potential confounding factors by adjusting their analysis.

All in all, the researchers believe that glucosamine is a promising, low-cost, accessible candidate to prevent chronic diseases. Their research suggests that glucosamine benefits might extend beyond joint health, where it is currently employed. However, given that this study cannot establish a causal effect, future research should more directly address causality and establish a better understanding of the molecular processes behind the observed associations.

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future.

Literature

[1] He, J., Ma, Y., Jiang, Y., Ji, J., & Song, F. (2025). Regular glucosamine supplementation and risk of age-related chronic diseases: evidence from a propensity score-matched cohort study. Aging clinical and experimental research, 37(1), 259.

[2] Ma, H., Li, X., Zhou, T., Sun, D., Liang, Z., Li, Y., Heianza, Y., & Qi, L. (2020). Glucosamine Use, Inflammation, and Genetic Susceptibility, and Incidence of Type 2 Diabetes: A Prospective Study in UK Biobank. Diabetes care, 43(4), 719–725.

[3] Vo, N. X., Le, N. N. H., Chu, T. D. P., Pham, H. L., Dinh, K. X. A., Che, U. T. T., Ngo, T. T. T., & Bui, T. T. (2023). Effectiveness and Safety of Glucosamine in Osteoarthritis: A Systematic Review. Pharmacy (Basel, Switzerland), 11(4), 117.

[4] Dalirfardouei, R., Karimi, G., & Jamialahmadi, K. (2016). Molecular mechanisms and biomedical applications of glucosamine as a potential multifunctional therapeutic agent. Life sciences, 152, 21–29.

[5] Ma, H., Li, X., Sun, D., Zhou, T., Ley, S. H., Gustat, J., Heianza, Y., & Qi, L. (2019). Association of habitual glucosamine use with risk of cardiovascular disease: prospective study in UK Biobank. BMJ (Clinical research ed.), 365, l1628.

[6] Li, G., Zhang, X., Liu, Y., Zhang, J., Li, L., Huang, X., Thabane, L., & Lip, G. Y. H. (2022). Relationship between glucosamine use and the risk of lung cancer: data from a nationwide prospective cohort study. The European respiratory journal, 59(3), 2101399.

[7] Li, Z. H., Gao, X., Chung, V. C., Zhong, W. F., Fu, Q., Lv, Y. B., Wang, Z. H., Shen, D., Zhang, X. R., Zhang, P. D., Li, F. R., Huang, Q. M., Chen, Q., Song, W. Q., Wu, X. B., Shi, X. M., Kraus, V. B., Yang, X., & Mao, C. (2020). Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study. Annals of the rheumatic diseases, 79(6), 829–836.

Microglia

Microglial Aging Is Determined by Their Environment

A new preprint study from Calico has found that the local brain environment is the primary driver of microglial aging. After being transplanted into old brains, young cells adopted aged characteristics, but their susceptibility to these signals could be turned off [1].

Microglia grow old and irritable

Brain aging holds a special place in the longevity field as a strong limiting factor: even if we can rejuvenate the body by replacing its various parts and organs, the brain is what contains our memories and personality, hence it cannot be simply replaced. This makes rejuvenating the brain a crucial step in achieving meaningful lifespan extension.

Studies have consistently found that the support cells known as glia age faster than neurons. Of these glial cells, the brain’s specialized immune cells (microglia) are among the most profoundly affected by aging [2]. Aged microglia often develop a more aggressive, pro-inflammatory phenotype that is suspected to drive neurodegeneration [3].

One crucial question about microglial aging is about whether these cells age because of a pre-programmed internal clock (a cell-intrinsic process) or are pushed into an aged state by signals from their deteriorating neighborhood (a cell-extrinsic process). This study from Calico, the Alphabet-owned longevity company, was designed to test cell-intrinsic versus environmental effects by replacing microglia with donor myeloid cells across young and old brains.

Young cells for aged brains

The researchers developed a method to replace the native microglia in mice with new myeloid cells derived from the bone marrow of donor mice. They first produced a pool of donor hematopoietic stem cells (HSCs) taken from young female mice. The cells were genetically engineered to produce two extra proteins: an enhanced version of the green fluorescent protein (EGFP), which allows the tracking of cells that express it in vivo, and Cas9, an element of the CRISPR gene editing platform. This created “ready-to-edit” cells: to knock out a gene later in the study, the team simply needed to introduce a small piece of guide RNA to direct the pre-existing Cas9 to its target.

The bone marrow niche of the old recipient mice was then depleted to make room for donor stem cells. However, the researchers also needed to rid the brain of old microglia. This was done by adding a drug that inhibits CSF1R, a protein crucial for microglial survival. With the original microglia gone, the donor-derived myeloid cells circulating in the blood could now enter the brain. There, they settled down and became microglia-like cells.

With their system established, the researchers set out to investigate what happens when young, healthy ‘reconstituted cells’ are placed in an aged brain. Apparently, the environment is the dominant force. Young cells in old brains rapidly began to look and act old, especially in the cerebellum, adopting aged gene expression patterns. The researchers defined a “Cerebellar Accelerated Aging Signature” (CAAS), a molecular fingerprint of 403 genes, and watched the young cells in the old brain acquire this signature.

“What did the old brain tell the young cells? To get old, fast,” said Oliver Hahn, Ph.D., a principal investigator at Calico and the paper’s senior author, in an X thread. “The aged brain environment overrode the intrinsic youth of donor cells! These young ‘reconstituted cells’ acquired the molecular aging signatures we see in old microglia, an effect strongest in the cerebellum.”

To confirm that the brain environment could not only make young cells old but also make old cells young, the researchers performed the reverse transplantation. When transplanted into young brains, cells from old mice showed transcriptional and morphological rejuvenation.

Aging signals blocked

When the researchers compared the gene expression profiles of microglia from young and old brains, one of the strongest molecular patterns they found was a heightened pro-inflammatory interferon response signature. To see if dampening interferon response would rescue microglia aging, the team decided to knock out Stat1, a well-known master regulator of this signaling pathway.

Using their Cas9 “edit-ready” platform, the researchers produced Stat1-deficient young cells and repeated their repopulation protocol. Unlike in the previous experiment, these cells were largely protected from the rapid aging that the researchers had previously observed: they resisted the aging signals from the environment and did not activate the CAAS signature.

The researchers wanted to know which type of cells produced these aging signals. As it turned out, at least for the interferon response, the culprit was natural killer (NK) cells rather than T cells, which initially were the researchers’ primary suspect. Depleting NK cells in aged mice blunted the age-related interferon response in microglia.

“Our findings are clear,” Hahn said. “The local brain environment drives microglia aging, with NK cells acting as an unexpected upstream trigger. Crucially, this is blockable, as Stat1-KO shields young cells from pro-aging cues. This challenges simple ‘rejuvenation-by-replacement’ ideas. This is just the beginning. We’re now using this platform to map out other pro-aging signaling axes. We hope our new, scalable eHSC system will be a powerful resource for the field, enabling future in vivo screens to find new targets for neuroinflammation.”

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future.

Literature

[1] Gizowski, C., Popova, G., Shin, H., Mader, M. M., Craft, W., Kong, W., Shibuya, Y., Wranik, B. J., Fu, Y. C., Depp, C., Lin, T. D., Martin-McNulty, B., Yoo, Y., Tai, P.-H., Hingerl, M., Leung, K., Atkins, M., Fong, N., Jogran, D., … Hahn, O. (2025, September 7). Heterochronic myeloid cell replacement reveals the local brain environment as key driver of microglia aging [Preprint]. bioRxiv.

[2] Costa, J., Martins, S., Ferreira, P. A., Cardoso, A. M., Guedes, J. R., Peça, J., & Cardoso, A. L. (2021). The old guard: Age-related changes in microglia and their consequences. Mechanisms of ageing and development, 197, 111512.[3] Adamu, A., Li, S., Gao, F., & Xue, G. (2024). The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets. Frontiers in aging neuroscience, 16, 1347987.

[3] Adamu, A., Li, S., Gao, F., & Xue, G. (2024). The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets. Frontiers in aging neuroscience, 16, 1347987.

Brain effects

Study Boosts Brain Mitochondria, Rescues Memory in Mice

Scientists have found a way to directly stimulate the assembly of Complex I in mitochondria, rescuing memory deficits in mouse models of Alzheimer’s and frontotemporal dementia [1].

Mitochondrial signal transducers

Many neurodegenerative diseases, such as Alzheimer’s disease, are associated with mitochondrial dysfunction [2], which might lead to cells not working properly or dying off. However, it’s been difficult to determine whether mitochondrial problems are a root cause or a symptom of these diseases.

This uncertainty exists mainly due to the lack of reliable ways to specifically and quickly boost mitochondrial function in the brain. In a new study published in Nature Neuroscience, researchers from Inserm and the Université de Bordeaux, in collaboration with researchers from the Université de Moncton in Canada, inched closer to answering the question and maybe developing therapies for mitochondrial disorders.

In previous studies, the researchers worked on the role of guanine nucleotide-binding proteins (G proteins). Their main role is signal transduction: they typically sit inside the cell’s main outer membrane, linked to G protein-coupled receptors (GPCRs). When a signaling molecule, such as a hormone or a neurotransmitter, binds to a GPCR on the cell surface, the receptor activates its associated G protein, which initiates a downstream cascade of biochemical reactions within the cell, leading to a specific physiological change.

However, recent studies have found that G proteins exist also in mitochondrial membranes and regulate energy production [3]. The researchers reasoned that activating G proteins directly inside the mitochondria could rapidly ramp up the organelles’ activity and improve cognitive function.

The tool they built to influence mitochondrial Gs protein (“s” for the stimulatory subtype) is based on Designer Receptor Exclusively Activated by Designer Drugs (DREADD) technology. A DREADD is a receptor protein that has been altered so that it no longer responds to its natural activators but can be switched on by a specific and otherwise inert “designer drug,” such as clozapine-N-oxide (CNO).

The researchers also attached a sequence to the construct that would guide it directly to mitochondria, ensuring that it does not end up in other membranes. Using high-resolution microscopy and protein analysis, they confirmed that the new tool was successfully delivered and embedded into the outer membrane of mitochondria in various cell types and in the hippocampi of mice.

A phosphorylation cascade triggers energy production

The experiments showed that activating mitoDREADD-Gs with CNO had a direct and rapid effect on mitochondrial function. In cells and hippocampal tissue expressing the tool, CNO treatment significantly increased mitochondrial membrane potential, which is an indicator of energy-producing activity, and oxygen consumption rate (OCR), which directly measures mitochondrial respiration. The team also used a control DREADD that wasn’t targeted to the mitochondria, and it had no such effect.

“This work is the first to establish a cause-and-effect link between mitochondrial dysfunction and symptoms related to neurodegenerative diseases, suggesting that impaired mitochondrial activity could be at the origin of the onset of neuronal degeneration,” said Giovanni Marsicano, Inserm research director and co-senior author of the study.

The researchers also confirmed that mitoDREADD-Gs works by activating the naturally present (endogenous) Gs protein. When cells genetically engineered to lack Gs were used, the tool failed to boost mitochondrial activity.

Investigating the entire mechanism, the team found that the mitochondrial Gs protein triggered a cascade of phosphorylation, starting with the enzyme protein kinase A (PKA). The ultimate target turned out to be NDUFS4, a component of Complex I of the electron transport chain, the machinery in the heart of mitochondrial energy production, promoting its assembly and activity.

Memory rescued in mice

The researchers then turned to two mouse models: one of of frontotemporal dementia (FTD) and another Alzheimer’s disease. They first confirmed that these mice had lower mitochondrial respiration and reduced PKA activity in the hippocampus, a brain region critical for memory.

In both models, when mitoDREADD-Gs was expressed in the hippocampi of these mice and activated with CNO, the animals’ performance in novel object recognition (NOR), a common memory test in rodent studies, was fully restored to the level of healthy mice. The control (non-mitochondrial) DREADD had no effect.

“These results will need to be extended, but they allow us to better understand the important role of mitochondria in the proper functioning of our brain. Ultimately, the tool we developed could help us identify the molecular and cellular mechanisms responsible for dementia and facilitate the development of effective therapeutic targets,” said Étienne Hébert Chatelain, professor at the Université de Moncton and co-senior author of the study.

“Our work now consists of trying to measure the effects of continuous stimulation of mitochondrial activity to see whether it impacts the symptoms of neurodegenerative diseases and, ultimately, delays neuronal loss or even prevents it if mitochondrial activity is restored,” added Luigi Bellocchio, Inserm researcher and co-senior author of the study.

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future.

Literature

[1] Pagano Zottola, A. C., Martín-Jiménez, R., Lavanco, G., Hamel-Côté, G., Ramon-Duaso, C., Rodrigues, R. S., … & Hebert-Chatelain, E. (2025). Potentiation of mitochondrial function by mitoDREADD-Gs reverses pharmacological and neurodegenerative cognitive impairment in mice. Nature Neuroscience, 1-14.

[2] Wang, W., Zhao, F., Ma, X., Perry, G., & Zhu, X. (2020). Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances. Molecular neurodegeneration, 15(1), 30.

[3] Suofu, Y., Li, W., Jean-Alphonse, F. G., Jia, J., Khattar, N. K., Li, J., … & Friedlander, R. M. (2017). Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release. Proceedings of the National Academy of Sciences, 114(38), E7997-E8006.

Protein aggregate

A Mechanism Behind Protein Aggregation Discovered

Scientists have found a pathway that regulates protein aggregation, a cause of several age-related neurodegenerative diseases.

United by abnormal protein aggregation

Most neurodegenerative diseases are age-related, and many of them are similar in other ways. For instance, amyotrophic lateral sclerosis (ALS), Huntington’s disease, and Alzheimer’s disease have all been linked to abnormal protein aggregation [1], albeit with different proteins involved. This is unsurprising, since one of the key hallmarks of aging is the decline of proteostasis.

While the protein culprits are different between these diseases, this similarity hints at possible common mechanisms that scientists have been looking for. In a new study from the University of Cologne, published in Nature Aging, the researchers might have made a big leap towards understanding these common causes.

One protein causes several others to aggregate

The team worked with models based on C. elegans, a nematode worm and a workhorse of longevity research. Researchers focused on a signaling pathway involving two proteins, EPS-8 and RAC. Previous work had found that as C. elegans ages, EPS-8 accumulates, which upregulates RAC signaling. This hyperactivation shortens the worm’s lifespan [2].

The key question was whether this known aging pathway could also be the trigger for disease-related protein aggregation. To find out, the team used genetically engineered worms that express the toxic human proteins responsible for Huntington’s (polyglutamine, or polyQ) and ALS (mutant FUS and TDP-43).

Using RNA interference (RNAi) to knock down the eps-8 gene and its partner rac genes, the researchers observed a significant decrease in the aggregation of all the disease-related proteins. This effect occurred without simply reducing the total amount of the protein, suggesting that it specifically prevented the clumping process.

This reduction in protein clumps had a direct functional benefit. The worms’ neuronal health was preserved, as evidenced by their improved performance on behavioral tests like avoidance response and the ability to sense and move towards chemicals (chemotaxis).

Digging for the mechanisms

To confirm that high levels of EPS-8 were the direct cause, the team used a mutant worm producing a reinforced form of EPS-8. This mutation increases the protein’s levels from a young age. The worms showed accelerated protein aggregation and earlier onset of neuronal deficits, directly linking EPS-8 accumulation to the disease pathology.

The researchers found that the overactivated EPS-8/RAC pathway drives aggregation through at least two downstream mechanisms. The first one is excessive actin polymerization, which leads to the overproduction and destabilization of the cell’s actin cytoskeleton. While the exact link isn’t definitive, the authors hypothesize that a destabilized actin cytoskeleton could promote protein aggregation by causing actin to form aggregates, which then act as “seeds” for other toxic proteins to clump onto.

The second mechanism is hyperactivation of another signaling protein called JNK. Knocking down the worm’s JNK homolog, kgb-1, also effectively prevented protein aggregation. The authors suggest that the chronic upregulation of the JNK stress pathway during aging may lead to broader cellular changes that hurt the cell’s ability to maintain healthy proteostasis.

Moving further upstream, the team investigated why EPS-8 accumulates with age. They discovered that the culprit is a deubiquitinating enzyme (DUB), USP-4. Proteins in a cell are often tagged with a ubiquitin molecule to mark them for recycling. DUBs remove these tags, which prevents protein degradation.

The study showed that as worms age, levels of usp-4 increase. This leads to more EPS-8 being deubiquitinated and saved from destruction, which causes its accumulation. Importantly, knocking down usp-4 in aging worms reduced protein aggregation and extended their lifespan.

Confirmed in human cells

To confirm that these findings are relevant to humans, the researchers replicated their experiments in human cell models, including motor neurons derived from induced pluripotent stem cells (iPSCs) taken from an ALS patient. Remarkably, the results were similar. Knocking down human EPS-8 or USP-4 significantly reduced the aggregation of mutant HTT, FUS, and TDP-43 proteins. In the ALS patient-derived motor neurons, this intervention also reduced apoptosis and necroptosis, two forms of cell death.

“We are delighted to uncover a molecular mechanism that could shed light on how aging contributes to diseases like ALS and Huntington’s,” said first author Dr. Seda Koyuncu. “For years, we’ve known that age is the major common risk factor for different neurodegenerative diseases. However, how exactly age-related changes contribute to these diseases remains largely unknown. This study may contribute to filling in a part of that puzzle.”

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future.

Literature

[1] Hommen, F., Bilican, S., & Vilchez, D. (2022). Protein clearance strategies for disease intervention. Journal of Neural Transmission, 129(2), 141-172.

[2] Koyuncu, S., Loureiro, R., Lee, H. J., Wagle, P., Krueger, M., & Vilchez, D. (2021). Rewiring of the ubiquitinated proteome determines ageing in C. elegans. Nature, 596(7871), 285-290.

Calendar date

Some Bioethicists Promote Lifespan Limitation

A paper published in Bioethics makes a startling case for people to die at 100 years old rather than live as long as they might choose.

Deathism is relatively rare

People who wholeheartedly believe that human lifespans should be restricted to a pre-defined span are not common. Most popular concerns around life extension involve its feasibility and cost along with the perception that a handful of gerontocrats will use it to maintain power even while chronologically younger people die of age-related diseases. This frequently dovetails with very real concerns about the cost and accessibility of medical care in general. What therapies are developed, how they can be put into clinical practice, and who ultimately pays for them are the topics of greatest concern; very few people argue against the idea that people should have accessible therapies.

Survey results tell us less about people’s true desires than their actions; in the economics world, this is known as ‘revealed preferences’. For example, if someone states the desire to eat healthy food, but spends hundreds of dollars a month on unhealthy food, we know that person’s true, revealed preference. Similarly, if someone states the desire to die before getting old, but then voluntarily opts for intensive treatment while gradually succumbing to currently incurable age-related diseases, we can surmise that this person did not actually want to die after all; given the notoriously and consistently high cost of end-of-life care [1], it is clear that this is the most common option.

People who do choose to die at advanced ages are not making the choice between healthy life and death; they are choosing to die immediately rather than suffer increasingly painful and debilitating medical conditions before dying later. If such people were instead offered a comprehensive suite of rejuvenation technologies capable of restoring their youthful health, it is a very safe bet that the overwhelming majority of them would gladly take it. Bringing such technologies into fruition is the business of the Lifespan Research Institute and the life extension field as a whole.

Under normal circumstances, human beings would, given the choice, rather not die; this is heavily backed up by everyday experience and medical expenditure data. Even people who engage in dangerous or self-destructive actions are known to be chasing short-term pleasure over long-term survival. Most people who ‘live fast, die young’ do not actually want to die young; they’re simply more interested in living fast. Of the people who soberly claim to want to die young, it is usually more accurate to say that they want to avoid the problems involved with being old.

With this background of human experience in mind, it is rare to see a published paper arguing for finite lifespans, but this is what was authored by a team led by the Project Director of Biotechnology and the Humanities at the University of Oxford.

A case for death?

This paper was written as a rebuttal to Ingemar Patrick Linden’s The Case Against Death, a well-known book that is commonly found on the shelves of life extensionists everywhere (including in China, where the translation was published by Immortal Dragons). Importantly, neither Linden’s book nor this rebuttal discusses the mechanics of how indefinite lifespans might be achieved; instead, for the sake of argument, it is assumed that everything involved in aging has been effectively cured. In such a world, the authors of this paper imply, it would be better for people to simply die at age 100 rather than continue to exist past that.

The bulk of this paper is focused on a concept of ‘self-giving love’ that ties into aging and death. Specifically, the authors consistently refer to people as “embodied beings” that have a shared web of relationships, and they refer to meaningful life itself as being spent fulfilling the needs of other people. This theme of gradual self-sacrifice is found throughout the paper, such as “a 100-year time span could provide an important reference for the amount of anticipated work remaining in relation to spending one’s life in service to others.” and “it would be disorienting and disheartening to run a race with no obvious end.”

Death, in this view, is a reprieve from a life of constant toil, making it questionable what ‘love’ actually means in this context. Obviously, the authors do not want to continue these relationships forever; rather, such human interactions are portrayed as an obligation, a duty, rather than something they want to keep doing. Despite the authors’ claims of meaning and purpose, the subtext remains that such a life is a long, tedious chore that will be mercifully, fortunately ended by death; simply giving up or setting aside such relationships is not seriously considered as an option.

They mention that some people may choose to die and leave others behind, leaving scars on the survivors: “Would it not correspondingly become difficult to love, and so open your heart to another, after watching so many people die?” Of course, such traumatic events very often happen due to age-related diseases right now.

There is also a Malthusian element: “We will only say that one might reasonably conclude it is an act of necessary love to forgo the inhibition of aging so as to not risk the imposition of birth restrictions, or else transform society in other radical ways—especially without the full consent of any particular populace.” The consent of the people being told that they have an obligation to die is not mentioned.

The dystopian elephant in the room

Like most works on ethics, this paper concerns itself with what people should do and does not concern itself with how such a world would be achieved. For the indefinite-lifespans world, it’s easy to envision; people go to the doctor to have their aging treated. For a world in which people have access to indefinite-lifespan technologies but are instead consigned to die at age 100, there must be some sort of enforcement mechanism; the mechanics of how this might work are left as an exercise for the reader.

Given that such a future dystopia is highly unlikely to actually occur, and extraordinarily few people choose to suddenly die while experiencing healthy lifespan, regular readers might wonder why we’re choosing to take this seriously instead of summarizing a scientific advancement. The problem, as always, is one of resource allocation; this was published in a journal with the backing of a major university, meaning that it might reach the eyes of decision makers. If such people are swayed by arguments against longer lives, then vital projects might not get funded, critical breakthroughs might occur much later than they otherwise could have, and a great number of human beings might suffer and die.

This also underscores why pro-longevity activism is surprisingly important. People want to live, but they might not know that the processes of aging are targetable, understandable, and potentially treatable. Getting this information out, and making sure that productive work is being done to fight against these harmful processes, is necessary for us to be able to choose life over death.

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future.

Literature

[1] Hoover, D. R., Crystal, S., Kumar, R., Sambamoorthi, U., & Cantor, J. C. (2002). Medical expenditures during the last year of life: findings from the 1992–1996 Medicare current beneficiary survey. Health services research, 37(6), 1625-1642.

Cancer cells

Cancer Cells Transfer Mitochondria to Fibroblasts

Scientists have discovered that cancer cells recruit fibroblasts to support tumor growth by transferring mitochondria into them. Blocking this process might be a new way to fight the deadly disease [1].

It goes both ways

Cancer doesn’t act alone. Its success often hinges on recruiting neighboring cells into cooperation with cancer cells. Sometimes, those neighboring cells donate mitochondria to cancer cells [2], boosting the latter’s metabolism and promoting tumor growth.

In skin cancer, for instance, mitochondrial transfers from cancer-associated fibroblasts (CAFs) to cancer cells have been documented. Now, for the first time, a team of researchers from ETH Zurich has demonstrated that the opposite phenomenon also takes place: the transfer of mitochondria from cancer cells to CAFs.

CAFs are a key component of the tumor microenvironment [3]. They build and maintain the tumor’s support system by laying down stiff extracellular matrix (ECM), secreting growth factors and inflammatory signals, reshaping metabolism, promoting blood vessel growth (angiogenesis), and dampening immune responses.

Supercharging and reprogramming the fibroblasts

In their paper published in Nature Cancer, the researchers describe co-culturing highly malignant A431 skin cancer cells with human primary fibroblasts (HPF). By labeling mitochondria in the cancer cells, they were able to confirm that some of them ended up in the fibroblasts.

Mitochondrial transfer is a widespread phenomenon, such as in injury healing, and it can happen in several ways. However, the researchers were able to rule out all but one method: transfer via tunneling nanotubes (TNTs), thin, actin-based membrane bridges that directly ferry organelles and signals between cells. Using a drug that disrupts the formation of actin filaments strongly inhibited the transfer.

These results suggested that cancer cells extend TNTs to physically deliver their mitochondria directly into fibroblasts. The team also confirmed this phenomenon wasn’t unique to skin cancer, as they observed the same transfer happening with breast and pancreatic cancer cells.

Why would cancer cells transfer valuable mitochondria to other cells? As the researchers found, in HPFs that received mitochondria from cancer cells, several genes related to CAF phenotypes and ECM building were upregulated, and proliferation got a boost. Basically, it looked like mitochondrial transfer from cancer cells caused HPF reprogramming toward CAFs.

“Cancer cells actually exploit a mechanism for their own purposes that is beneficial in the event of injury. This allows them to grow into malignant tumors,” said cell biology professor Sabine Werner, a co-lead author of the study.

Assays showed increased oxidative phosphorylation and proton leak in recipient HPFs, which indicates that the cell’s energy-producing machinery is working overtime. Treatment with oligomycin, which impedes energy production by mitochondria, blocked both CAF marker induction and proliferation.

To prove that the mitochondria alone were responsible for this transformation, the scientists isolated mitochondria directly from cancer cells and transplanted them into normal fibroblasts. This was sufficient to induce the same CAF-like changes, confirming that the transferred mitochondria are the primary drivers of this reprogramming.

Crucially, not just any mitochondria would do. Mitochondria from non-cancerous cells had little effect, whereas mitochondria from more malignant cancer cells had a stronger effect. When dysfunctional mitochondria were transferred (from cancer cells with depleted mitochondrial DNA), the fibroblasts were not reprogrammed and did not support tumor growth in mice.

The master regulator of the transfer

In vivo, co-injecting A431 cells with fibroblasts that had received A431 mitochondria yielded bigger tumors and increased angiogenesis. That in-vivo impact raised the question of what tumor factor controls the handoff.

By analyzing gene expression data from human skin cancers, the team zeroed in on several genes involved in mitochondrial trafficking. One protein stood out: MIRO2, which was significantly overexpressed in cancer cells, particularly at the invasive edges of tumors where they interact with fibroblasts.

MIRO2 acts like a molecular motor, linking mitochondria to the cell’s transport network to control their position. The team hypothesized that cancer cells hijack MIRO2 to move their mitochondria out for delivery.

When RNA interference was used to reduce MIRO2 levels in cancer cells, the cells’ mitochondria clustered around the nucleus instead of spreading out. This reduced the cells’ ability to transfer mitochondria to fibroblasts and to convert them into CAFs. Conversely, increasing MIRO2 levels in cancer cells boosted their mitochondrial transfer activity.

“This protein is produced in very high quantities in cancer cells that transfer their mitochondria,” Werner mentioned.

When researchers injected cancer cells with depleted MIRO2 into mice, the cells failed to form tumors. However, when those MIRO2-deficient cells were coinjected with fibroblasts that had been pre-loaded with cancer mitochondria, this combination did induce tumor growth, suggesting that MIRO2’s role was to cause fibroblasts’ reprogramming into CAFs, and that that role was crucial for cancer development.

“The MIRO2 blockade worked in the test tube and in mouse models. “Whether it also works in human tissue remains to be seen,” said Werner. “If successful, such an inhibitor could be transferred to clinical applications in the longer term.”

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future.

Literature

[1] Cangkrama, M., Liu, H., Wu, X., Yates, J., Whipman, J., Gäbelein, C. G., … & Werner, S. (2025). MIRO2-mediated mitochondrial transfer from cancer cells induces cancer-associated fibroblast differentiation. Nature Cancer, 1-20.

[2] Zampieri, L. X., Silva-Almeida, C., Rondeau, J. D., & Sonveaux, P. (2021). Mitochondrial transfer in cancer: a comprehensive review. International journal of molecular sciences, 22(6), 3245.

[3] Sahai, E., Astsaturov, I., Cukierman, E., DeNardo, D. G., Egeblad, M., Evans, R. M., … & Werb, Z. (2020). A framework for advancing our understanding of cancer-associated fibroblasts. Nature Reviews Cancer, 20(3), 174-186.

Heart analysis

A Non-Viral Gene Therapy Restores Mouse Hearts

A recent study investigated the roles of brown adipose tissue and a lipid-controlling hormone, 12,13-diHOME, in cardiac health. The researchers examined the molecular mechanisms behind 12,13-diHOME’s effects on the hearts of aged mice [1].

The aging heart

Aging leads to many cardiovascular system-related changes, which are connected to disruptions in Ca2+ metabolism [2]. Similarly, brown adipose tissue (BAT), which protects against metabolic and cardiovascular diseases [3], also decreases with age.

Previous work from this group linked BAT to improved calcium signaling and cardiac function in mice and identified a molecule, 12,13-diHOME, a lipid-controlling hormone (lipokine) that mediates this connection in young, healthy mice [4]. In this study, those researchers investigated this relationship during aging and its connection to the age-related decline in cardiovascular health.

Transplanting fat

The age-dependent decline in the BAT’s thermogenic function is well documented [3], but the BAT’s endocrine function is less explored. To investigate this, the researchers measured circulating lipids in the plasma of human participants aged 65-90, young people aged 18-35, and aged and young male mice. Unsurprisingly, age affected lipid signaling in both humans and mice, with some overlap between the two species, including seven oxylipins that were decreased in both aged mice and humans compared to young controls. One of them is 12,13-diHOME, a molecule that is released by BAT and has a positive impact on cardiac function [4].

Transplanting BAT from young mice to the visceral cavities of sex-matched aged mice led to improvements in many metrics of cardiac function and health in these mice, suggesting that BAT transplantation ameliorated their age-related cardiac problems. This was judged to be through the release of 12,13-diHOME, as BAT transplantation increased circulating 12,13-diHOME in aged mice. Such beneficial effects were not observed when white adipose tissue was transplanted, suggesting that these effects are specific to BAT.

A non-viral gene therapy approach

Since transplanting fat from young donors to the elderly would be quite a cumbersome procedure to apply in a clinical setting, the researchers tested whether acute 12,13-diHOME treatment would have the same effect. Injecting male and female aged mice with 12,13-diHOME improved cardiac functions in male but not female mice.

12,13-diHOME has a short half-life. Just 30 minutes after injection, the researchers did not observe increased plasma levels of 12,13-diHOME. To remedy this, the researchers turned to a non-viral gene therapy approach: tissue nanotransfection (TNT), which allowed them to test the impact of sustained 12,13-diHOME increase. They inserted all the genes necessary to produce 12,13-diHOME on a string of circular DNA, which was delivered to mouse skin cells with a short electric pulse once a week for 6 weeks. This allowed for 12,13-diHOME overexpression in those cells and increased its levels in circulation, leading to improvements in cardiovascular health and function in both male and female aged mice.

“In just six weeks, we were able to really negate a lot of the effects of cardiovascular aging by using TNT to increase 12,13-diHOME. The results were quite striking with improvements to ejection fraction and the heart’s pumping cycles,” said Daniel Gallego-Perez, Ph.D., professor and Edgar C. Hendrickson Chair in Biomedical Engineering at The Ohio State University.

Male-specific mechanism

To understand the observed changes at the molecular level, the researcher compared the gene expression in the heart tissues of young mice, BAT-transplanted aged mice, and an aged control group; all of these mice were male. Gene expression analysis showed increased ER stress markers in the aged control group, while BAT-transplant mice had levels akin to the young mice. The same was found to be true for male mice given the gene therapy.

Surprisingly, the researchers didn’t observe any changes in ER stress among female mice, possibly because of lower baseline ER stress levels in females.

Further explorations of the mechanism involved experiments in mice lacking neuronal nitric oxide synthase (nNOS), an enzyme that produces a nitric oxide signaling molecule. The same group showed before that nNOS was necessary for 12,13-diHOME’s beneficial effects on cardiac function [4]. This study found that ER stress and cardiac function didn’t improve following the 12,13-diHOME gene therapy in the nNOS-deficient mice, suggesting the beneficial effect on cardiac function is mediated by 12,13-diHOME.

The researchers also showed the critical role of Ca2+/calmodulin-dependent protein kinase II (CaMKII). CaMKII is known to be a mediator of ER stress, has been linked to cardiac dysfunction, and increases in the heart with aging [5, 6].

Mice with overexpressed 12,13-diHOME had reduced pCaMKII (activated CaMKII) in the hearts of male but not female mice. The authors suggest that reduced baseline pCaMKII levels in aged female but not aged male mice might be why this is ineffective in female mice.

Hyperactivation of CaMKII in primary murine fibroblasts led to reduced mitochondrial respiration and increased ER stress; however, adding 12,13-diHOME to the cells reversed those CaMKII-induced effects. Similar effects were observed in human fibroblasts. The authors concluded that “these data provide a mechanism for 12,13-diHOME to modulate CaMKII activity and ER stress in a model of aging.”

Overcoming limitations

Kristin Stanford, Ph.D., the leader of the group who conducted the study and a professor at the Department of Surgery at the Ohio State University College of Medicine and associate director of the Dorothy M. Davis Heart and Lung Research Institute, summarized: “One of the biggest things we see with aging is cardiovascular disease, which increases dramatically in patients who are over 65. Now we’re correlating it to a decrease in the lipokine 12,13-diHOME, and we’re showing directly that when we increase this lipokine that we can essentially rescue cardiac function.”

The results obtained in this study align with previous data showing significantly decreased levels of circulating 12,13-diHOME in male and female patients with cardiovascular disease compared to age-matched healthy people [4]. However, previous studies did not explore 12,13-diHOME’s therapeutic potential due to its short half-life. This study overcame this obstacle by using a non-viral gene therapy approach.

While it successfully improved cardiovascular health and function in both male and female aged mice, the mechanism behind 12,13-diHOME’s positive impact is sex-specific, and the researchers were only able to identify the mechanisms and molecular processes at play in males; future investigation into understanding its mechanics in females is necessary. Also, while current research showed promising results, it was done in mice; therefore, there is still a need for human testing.

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future.

Literature

[1] Nirengi, S., Buck, B., Das, D., Peres Valgas da Silva, C., Calyeca, J., Baer, L. A., Huang, H. L., Vidal, P., Dewal, R. S., Pinckard, K. M., Félix-Soriano, E., Hernandez-Saavedra, D., Gerea, A., Dathathreya, K., Duarte-Sanmiguel, S., Saldana, T. A., Hookfin, H. L., Gorr, M. W., Bussberg, V., Aristizabal-Henao, J. J., … Stanford, K. I. (2025). 12,13-diHOME protects against the age-related decline in cardiovascular function via attenuation of CaMKII. Nature communications, 16(1), 7088.

[2] Janczewski, A. M., & Lakatta, E. G. (2010). Modulation of sarcoplasmic reticulum Ca(2+) cycling in systolic and diastolic heart failure associated with aging. Heart failure reviews, 15(5), 431–445.

[3] Becher, T., Palanisamy, S., Kramer, D. J., Eljalby, M., Marx, S. J., Wibmer, A. G., Butler, S. D., Jiang, C. S., Vaughan, R., Schöder, H., Mark, A., & Cohen, P. (2021). Brown adipose tissue is associated with cardiometabolic health. Nature medicine, 27(1), 58–65.

[4] Pinckard, K. M., Shettigar, V. K., Wright, K. R., Abay, E., Baer, L. A., Vidal, P., Dewal, R. S., Das, D., Duarte-Sanmiguel, S., Hernández-Saavedra, D., Arts, P. J., Lehnig, A. C., Bussberg, V., Narain, N. R., Kiebish, M. A., Yi, F., Sparks, L. M., Goodpaster, B. H., Smith, S. R., Pratley, R. E., … Stanford, K. I. (2021). A Novel Endocrine Role for the BAT-Released Lipokine 12,13-diHOME to Mediate Cardiac Function. Circulation, 143(2), 145–159.

[5] Timmins, J. M., Ozcan, L., Seimon, T. A., Li, G., Malagelada, C., Backs, J., Backs, T., Bassel-Duby, R., Olson, E. N., Anderson, M. E., & Tabas, I. (2009). Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways. The Journal of clinical investigation, 119(10), 2925–2941.

[6] McCluskey, C., Mooney, L., Paul, A., & Currie, S. (2019). Compromised cardiovascular function in aged rats corresponds with increased expression and activity of calcium/calmodulin dependent protein kinase IIδ in aortic endothelium. Vascular pharmacology, 118-119, 106560.

Ambulance back

Two People Almost Died at RAADfest. We Went to the Experts.

Two people nearly died, and several more sought treatment, after receiving peptide injections at the last RAADfest in Las Vegas. We might not know what happened until the ongoing investigations are concluded, but we asked several experts to share their thoughts on the broader context of unproven “rejuvenation therapies.”

The nightmare scenario

Admittedly, progress in the longevity field has been rather slow. A quarter of a century after the field rose to prominence, no approved, dedicated anti-aging therapies exist; a handful of promising treatments are working their way through the notoriously convoluted, slow, and expensive approval system. This frustrates many people, prompting them to try options that may not have been thoroughly tested for safety and efficacy.

Such treatments might include everything from dietary supplements to stem cells, off-label drugs, and gene therapies, and the market is growing fast. Longevity clinics are a new fad, as is longevity-oriented medical tourism. People want to live longer, healthier lives and are willing to shell out money and take certain risks to fulfill their dream. There’s nothing inherently bad about this, of course. However, it is important that the risks and benefits are faithfully communicated to them.

The mainstream media leans towards sensationalism and alarmism when it comes to people self-medicating or receiving treatments outside of the healthcare system’s rigid framework. Longevity enthusiasts, however, are aware that there is substantial evidence – even if mostly preclinical – supporting at least some experimental treatments. Many people also believe that people should have more leeway in choosing their own healthcare.

Yet, the risks from unproven therapies, unscrupulous providers, and even honest mistakes are also high. A nightmare scenario, often discussed on conference sidelines and in online debates, is that someone will eventually end up dead after receiving a “rejuvenation therapy,” which would draw scrutiny and suspicion from both regulatory bodies and the public and end up hamstringing the nascent longevity field.

The RAADfest debacle

This is what almost happened several weeks ago at the Revolution Against Aging and Death Festival, commonly known as RAADfest, one of the world’s largest, most colorful, and longest-running longevity conferences. Organized by the Coalition for Radical Life Extension, it featured solid scientific programming, as well as, for the first time, the “RAADclinic”, a hall where several providers offered longevity diagnostics and therapies. According to the coalition’s spokesperson, RAADfest hosted the event, but the therapies in question were provided independently. These ranged from benign ultrasound-based bone density scans to peptide injections administered directly at the booth.

On the last day of the conference, two women, 38 and 51 years old, were admitted to a Las Vegas hospital in critical condition after receiving peptide shots at the booth overseen by Kent Holtorf, MD, founder of the Holtorf Medical Group. Holtorf is licensed in California, but not in Nevada, although he said that, for the conference, he hired a practitioner who is.

According to ProPublica, which broke the story, “The two women who were taken by ambulance to the hospital reported feeling as if their tongues were swelling and had trouble breathing and increased heart rates. By the time they reached the hospital, one was already intubated, and the other had lost muscle control in her neck and couldn’t open her eyes or communicate with doctors.”

The Las Vegas police department originally reported that up to seven people sought treatment after receiving peptide injections at Holtorf’s booth. However, according to the Coalition for Radical Life Extension, the Southern Nevada Health District concluded its review on July 22, 2025, confirming only the two severe cases. Both patients have recovered since then.

Full of potential – and risks

Peptides are short chains of amino acids (40 residues or fewer in the US regulation), while proteins usually contain hundreds. Like proteins, peptides interact with other biomolecules: proteins, DNA, and RNA. This can be used for therapeutic effect or to shuttle various molecular cargoes. Peptides are generally more stable, less immunogenic, and more easily administrable than complete proteins. The small size also helps with the regulatory process.

The biggest peptide success story is of the GLP-1 receptor agonists, such as Ozempic. There is a handful of other approved peptide-based therapies, and many more are under development and review. Being enzyme-sensitive, peptides are typically administered by injection, but oral routes are becoming increasingly feasible. For instance, orally administered collagen peptides have gained popularity in the longevity community.

However promising, peptides carry risks, including immunogenicity and off-target binding. Their regulation in the US is, actually, too lax, according to Dr. Matt Kaeberlein, a prominent geroscientist who often decries overregulation by the FDA. Kaeberlein recorded a podcast episode about the incident at RAADfest, in which he criticizes Holtorf’s handling of the situation. Kaeberlein himself gave a talk at the conference and witnessed “therapeutic exosomes for longevity” being administered intravenously in a hotel room (exosomes are vesicles secreted by cells; there are currently no approved exosome-based treatments). Recently, Kaeberlein has been speaking out about the dangers of such unapproved therapies.

The regulatory no-man’s-land

While we are not in a position to estimate compliance, some important corners might have been cut here. Holtorf refused to clarify to ProPublica which peptides were administered at the conference. However, only three are listed on the IV price list on his clinic’s website: BPC-157, tymosine beta 4 (TB-4), and tymosine alpha 1 (Tα1).

None of these is an approved drug in the US. The FDA places them on its public risk list for compounded products and instructs pharmacies not to manufacture them from raw ingredients for routine care, for reasons that include limited human evidence, products that are difficult to characterize and maintain purity, and a higher risk of adverse reactions. Basically, outside a properly run clinical trial, these peptides sit in a regulatory no-man’s-land: they are neither lawful supplements nor standard prescriptions.

Another problem is the way these therapies are marketed to the public. As with many such clinics, the IV menu on Holtorf’s clinic’s website lists several sweeping claims about the therapies it offers. For example, BPC-157, according to the document, “has displayed the unique ability to have significant rejuvenating properties throughout the gastrointestinal tract and proven to be an effective treatment for a variety of gastrointestinal conditions.” This goes well beyond the scarce human data that we have, and most available work isn’t for IV use.

“The statements do seem overstated,” says Kaeberlein, “though that’s not unusual in this space. Many physicians offering these kinds of services tend to make similar exaggerated claims.”

For him, however, this is the least of the problems: “While I’m not a supporter of that type of advertising or medical care, I’d put what happened in Vegas in a completely different category. Handing out prescription medications in a hotel setting – without, I assume, obtaining full medical histories or current health information – takes things to an entirely new level.”

Holtorf’s clinic did not respond to a list of questions we sent. To ProPublica, Holtorf said that “in 30 years of providing such treatments, he’s never seen such a reaction,” and that, having consulted an AI, he was now convinced that the problem was not with the peptides. While it is entirely possible that the problem was with how the drugs were compounded and administered, this in itself does not invalidate many of the concerns.

Where do we go from here?

What happened at RAADfest highlighted some well-known problems and contradictions in the longevity field. On the one hand, there is a sense of urgency that pushes some people to offer and others to try therapies that have not been rigorously tested for safety and/or efficacy. Many rightfully lament the increasingly lengthy and expensive regulatory process, which is not properly suited for rejuvenating therapies. There is a growing push to extend the “right to try” to all patients and all reasonably safe therapies, and to accelerate clinical trials by relaxing certain regulations and transitioning towards cost-effective methods, such as human organoids and in silico models.

On the other hand, a legitimate concern exists that the longevity movement might be overshadowed, compromised, and ultimately impeded by the murky wave of overblown claims, unfounded promises, unproven therapies, and flat-out “snake oil” cures. To make some sense of all this in the context of the RAADfest incident, we have turned to several prominent figures in the field with a series of questions.

Therapies that haven’t been properly tested for safety and/or efficacy – how bad are they for the overall standing of the longevity field?

Matt Kaeberlein, founder of Optispan:

This is a complex question, and even the premise – what it means for a therapy to be “properly tested” for safety or efficacy – can be debated. Informed people can disagree on how much evidence is “enough,” and the level of proof needed for efficacy depends partly on how confident we are in its safety. That said, I tend to think about these therapies in three broad categories:

FDA-approved drugs or procedures used off-label include rapamycin, SGLT2 inhibitors, metformin, therapeutic plasma exchange, and other interventions already approved for other indications. When prescribed by ethical, competent clinicians, these pose minimal reputational risk to the longevity field and may have substantial upside if shown to benefit healthspan or lifespan. Criticisms of responsible off-label prescribing often miss the mark; the real concern is unprofessional practice, not the concept of off-label use itself.

With supplements, the damage to the field’s credibility is significant – not because supplements can’t work, but because we have very few with solid human efficacy data. The industry is rife with deceptive marketing and weak oversight, creating strong incentives for companies to mislead and outright lie to consumers. Until the regulatory and economic incentives change, this sector will remain problematic and will continue to harm the public’s perception of longevity science.

Unapproved or illegal interventions, often delivered offshore, include many stem cell treatments, gene therapies, exosomes, and so on. Here, the risks are high both for patients and for the field’s reputation. Adverse outcomes are often unreported, but when they become public (e.g., the RAADFest incident), the media coverage is damaging and plays into a narrative that the longevity space is unsafe and exploitative.

The lack of quality control in many offshore clinics means patients are relying entirely on the trustworthiness of providers – and, frankly, many in this space are not trustworthy. I understand the motivation to explore promising therapies more quickly, especially given regulatory hurdles, but operating outside legal and ethical frameworks is not the right path forward for the field.

Reason, CEO of Repair Biotechnologies:

What does “properly tested” mean? It is hard to have a conversation around the challenges in medical development without having a defensible position on that term. The regulatory community, by which I mean some assembly of FDA staff, consultants in the quality industry, and established drug developers big enough to have a say in shaping standards, presently demands more than twice the cost and effort leading up to approval than was the case twenty years ago. Do we believe that 20 years past, drug development was radically unsafe?

Equally, Australia allows drugs to be introduced into human patients for the first time without full Good Manufacturing Process, without a central regulator, at the discretion of institutional review boards and clinical trial sites. It costs about half of what an equivalent effort would require in North America. 10% of all Phase 1 clinical trials take place in Australia. Do we believe that this lower degree of safety assurance is radically unsafe?

Various groups, from media to Big Pharma to government outlets, vigorously attack those who do not conform to the present high standards. It isn’t because these high standards are necessary: for many types of manufacturing and therapy, they are overkill many times over in terms of cost and requirements. We know this because safe drugs of this type were produced in past decades, with a much lesser degree of regulatory oversight and cost.

Zero risk is impossible, yet it is the goal. Medicine always has risk, patients must always assess those risks in full knowledge, and yet every layer of the system tries to remove that task from the patient, even to the point of making it impossible for the patient to find out details, costs, and more until after the fact.

Within the context of this environment, there will always be bad actors. There are bad actors out there throughout the system, inside it, and outside it, in all branches of medicine. Some of them get a pass because they play ball and deliver marginally effective drugs with meaningful side effects and sell out before the consequences arrive. Others are sued, go out of business, are shut down by regulators, or are otherwise punished at some point. None of this has halted medicine more generally, and none of this will halt the longevity field.

Oliver Medvedik, Chief Science Officer, Lifespan Research Institute:

I think this is a broader question that can be directed to any and all therapies that purport to have efficacy without adequate data suggesting this to be the case. At one extreme, we can see items for sale online and in chain pharmacies, such as “magnetic healing bracelets,” which have no data that they work, yet continue to be sold. At the other end of the spectrum, we have certain accepted surgical procedures in medicine, such as certain arthroscopic knee surgeries that are known to be no better than placebo sham surgeries.

Therefore, such untested “therapies” within the field of geroscience fall within this spectrum. They certainly make it more difficult for potential patients to navigate what is demonstrably proven to be effective, which in the field of geroscience, is precious little outside of proper exercise, diet, reducing stress, living within a supportive community, etc.

Andrew Steele, longevity advocate, author of “Ageless”:

I think it’s hard to generalize when there’s such a diversity of levels of evidence for different therapies – a longevity scientist self-experimenting with rapamycin is very different from a non-expert seeking out stem cells from an unlicensed practitioner. But I think overall we should be very cautious if we want longevity medicine to be perceived as a legitimate medical specialty. If people start to think that ‘longevity’ is unproven supplements or peptides, it’s just another communications challenge for a field that’s already facing numerous ethical questions, such as whether treatments will only be accessible to billionaires.

Ivan Morgunov, CEO of Unlimited Bio, a company offering gene therapies that passed Phase 1 safety trials at overseas locations:

Aging-related diseases kill around 120 people every minute (or 62 million a year). That’s thousands of times more than any realistic risk from experimental approaches. The real problem isn’t that some people try untested therapies, it’s that billions have no access to trying anything at all.

We must distinguish between two cases: when developers make exaggerated, unverified promises (which is indeed harmful), and when patients are honestly informed about the risks and status of a therapy (which is part of progress).

Just as spreading misinformation by some people doesn’t mean we should abolish free speech, if someone misleads people about treatments, that’s not a reason to ban all new approaches. Instead of blanket bans, we need transparency, informed consent, and accountability.

What is your opinion on medical tourism in the longevity context?

Kaeberlein:

I don’t think the core issue with medical tourism is that people are seeking it out. In fact, I’m fairly libertarian in my views on health care: I believe individuals who are truly informed about both the risks and potential benefits should have the right to pursue therapies, interventions, or diagnostics they believe are in their best interest. People should have agency over their own health, and the government should not unnecessarily stand in the way.

The real challenge is what it means to be “appropriately informed.” Too often, people engaging in medical tourism are not fully aware of the risks or of the lack of safeguards in place. Compounding this, many of the providers and product manufacturers (stem cells, exosomes, gene therapies, etc.) operating in this space are not the most professional, ethical, or trustworthy. Quality control is often minimal to nonexistent, and when something goes wrong, patients have little to no legal recourse.

Another major problem with medical tourism is that it rarely produces quality data on safety or efficacy. Even when patients do experience benefits, those outcomes are anecdotal and uncontrolled, making it impossible to distinguish between placebo effects and real biological impact. Adverse outcomes are often underreported or hidden – anyone in the space is aware of numerous reports of serious adverse outcomes that never come to light. So, the field as a whole learns very little. This lack of reliable data slows progress for everyone – patients, clinicians, and scientists alike – because we can’t confidently build on what works or avoid what doesn’t.

Reason:

Growth and maturity in the medical tourism industry is the best path towards bringing beneficial change to the development and provision of medicine in heavily regulated jurisdictions. Regulators do not respond to advocacy or attempts to bring change from within. The past few decades have amply demonstrated that.

Consider all the intense lobbying and patient advocacy that have taken place over a period in which the costs of regulatory compliance have more than doubled, and the number of new drug approvals has decreased. The only thing that will tame the regulators is for effective therapies to be widely available in other countries, a short plane flight away.

Currently, medical tourism suffers from being scattered, disorganized, hard to penetrate, to perform discovery, to determine quality. If that industry grows tenfold in size in the transition from therapies for very sick people, a small fraction of the population, to enhancement therapies that can be applied to nearly everyone, many of these challenges will likely be addressed, and in this growth lie the seeds of real change to the medical regulatory environment in the US and Europe.

Medvedik:

I think the context matters here. Will medical tourism be coupled with the patients being enrolled in a clinical trial where this data can be shared? Or will this be for an intervention that is being sold as a proven remedy, with no data being recorded or shared? If it’s the former, then I believe it can be a great way to move the field forward. If the latter, then buyers beware.

Steele:

Medical tourism exists on a sliding scale of risk, from travelling to save money on dental work to going somewhere with less stringent regulation to receive a treatment that isn’t approved at home. I think the issue for longevity medicine isn’t so much regulatory as that we don’t have any aging interventions that we know work! Personally, I only want to take longevity therapies that have been through rigorous testing and undergo rigorous quality control to make sure they contain what they say they do – meaning, broadly speaking, that they’d need the kinds of evidence that the FDA or the EU’s EMA would need to see to approve any experimental therapy.

Morgunov:

Medical tourism in the longevity field is an indictment of national healthcare systems. When people have to fly thousands of miles to get a treatment that could extend their life, it means something is deeply broken at home.

I’m doing this first and foremost for myself — to undergo a combination of gene therapies that, under classical regulations, I would never be allowed to have in my lifetime. Why should I need permission to save my own life?

What is your reaction to the particular incident at RAADFest?

Kaeberlein:

First, peptides as a class are often misunderstood. Some are FDA-approved and well-characterized, but many others have little to no human safety or efficacy data. They are bioactive molecules, no different from other classes of pharmaceutical drugs, and should be evaluated case by case based on available evidence, not treated as inherently “safe” or “natural.” Unfortunately, the space is filled with misinformation and hype.

That’s why I found it so concerning that a medical provider was administering peptide injections in the vendor hall at a major conference. We would never accept a physician handing out unapproved pharmaceutical drugs in that setting, and it should not happen with peptides either. I don’t know the exact details, whether this was within or outside conference guidelines, but regardless, it highlights a serious problem: peptides are being handed out far too casually, sometimes by licensed professionals, sometimes by people with no medical credentials at all.

This raises real questions about liability, patient safety, and the broader reputation of the longevity space. Unfortunately, when incidents like the one at RAADFest make headlines, the entire emerging field of “longevity medicine” takes a reputational hit. Some physicians in this area are outstanding, but many are not. And when questionable practices dominate the public narrative, the space begins to look unprofessional, unsafe, and even exploitative.

Reason:

Unfortunate, not surprising. At some point, there will be errors, there will be bad actors, and there will be people who don’t appreciate the level of risk they undertake in a particular circumstance. It is, of course, entirely unclear what exactly happened, the degree to which everyone involved was informed, and the beliefs they held about risk and safety; we may never know.

Consider that exactly this class of event occurs in hospitals throughout the country on a daily basis. It occurs quietly when physicians prescribe drugs off-label, and the normal human variability leads to an adverse reaction. It occurs when self-experimenters are incautious.

Zero risk in medicine is an illusion. An environment in which patients can trust without verifying is an illusion. It cannot exist. Some people believe it can or have had a run of good luck and misjudge their situation. Then there is cognitive dissonance when the dice turn up snake eyes.

Steele:

It’s tragic, and I hope that the two people affected are fully recovered or will soon be.

Morgunov:

Any severe health incident is serious and should be investigated. But let’s be honest: on that same day, more than 100,000 people worldwide died from aging-related diseases. Why is no one talking about that?

Think of self-driving cars: one crash doesn’t mean they should be banned, when hundreds die every day in accidents caused by human error, something that autonomous vehicles promise to avoid.

The same goes for anti-aging therapies: a single incident involving what is possibly an allergic reaction and emergency resuscitation shouldn’t outweigh millions of deaths every year. The solution isn’t to ban the technology, it’s to make it as safe and as accessible as possible.

(Medvedik chose not to comment on this particular episode)

Name one or more instances where regulation should be added and where it should be relaxed.

Kaeberlein:

In my view, the most obvious area where regulation should be strengthened is around supplements and other unapproved interventions that the FDA currently considers “generally recognized as safe.” I don’t think new rules are necessarily needed around demonstrating efficacy, but I do believe there should be clear, enforceable standards for honesty. Right now, many supplement companies in the longevity space make deceptive or outright false claims about their products. This kind of marketing not only misleads the public but also erodes trust in the entire field. Ensuring truthful communication would be a straightforward way to address this problem.

Another area where regulation doesn’t need to be expanded so much as enforced is with licensed medical professionals who knowingly operate outside the law or ethical standards of their profession. These laws exist, but enforcement is inconsistent at best.

That said, there are cases where the regulations themselves may need to evolve. Stem cells are a good example. I wouldn’t argue that regulation should simply be “relaxed,” but rather updated so that medical providers can responsibly deliver these therapies using products manufactured under strict quality standards, while also generating real-world data on safety and efficacy. Right now, the system gives us the worst of both worlds: little oversight of product quality and very limited collection of data that could actually tell us whether these treatments are safe or effective.

Reason:

The world would be a better place in the absence of most medical regulations. It is a cost that outweighs the benefits. The risk is still there, just now hidden, while patients are told to just trust rather than evaluate.

Medvedik:

Speaking from a US-centric view, I think the FDA should be much more proactive in testing our foods and supplements and regulating certain OTC medications that pose a high risk of lethality.

As for medical interventions, I do believe that regulations should be much more relaxed when it comes to adults who have terminal or painful illnesses to agree to being participants in clinical trials that the FDA presently deems to be too “high risk.”

Steele:

I think the issue of regulation in longevity science is important, but it can be a bit of a distraction – the most important thing we need is more funding for the field so we can do the kinds of large-scale trials that tell us whether treatments for aging work. Once this happens, I think we can have a more serious debate around regulation based on the known costs and benefits of tested therapies.

Morgunov:

Access to therapies with full and honest disclosure of the risks is a fundamental human right. The state shouldn’t stand between an informed adult and their decision to try to save their own life. Fifty years ago, maybe I could have accepted the current FDA rules. But today, we live in a unique moment where a technological leap — achieving longevity escape velocity — is theoretically possible. The millions of lives we could save outweigh the risks. We don’t need more brakes; we need accelerators.

Should people in the field get together and develop guidelines that would balance the need to accelerate progress with safety and PR concerns?

Kaeberlein:

Yes, I do think there’s real value in developing guidelines that balance accelerating progress with safety and public trust. The challenge, of course, is getting the right people in the room and ensuring the effort has a genuine impact. Too often, initiatives like this are launched with good intentions but struggle to move the needle in practice.

One of the difficulties today is that honesty and credibility don’t seem to carry the weight they once did. Dishonesty in the space has become increasingly normalized, which makes it harder for people with high ethical standards to feel motivated to invest their time in shaping guidelines. That said, I believe it’s exactly because of this environment that we do need a credible, science-driven framework for longevity medicine.

Such a framework should bring together experts in the biology of aging and geroscience, along with clinicians experienced in healthspan optimization and voices from regulatory and public policy. The goal would be to produce a kind of playbook for how to practice responsibly at the highest standards, rooted in evidence and integrity. Even if the immediate impact is uncertain, it could serve as an anchor point for the field and a benchmark for best practices.

Reason:

No. Everyone who can should focus on the only thing that makes a difference, which is building new medical technologies. There is a whole world full of people happy to fight over what to do with those technologies, what to say about those technologies, and who should have access to those technologies. Let them. They are irrelevant in the long term. Do we know or even care what regulators were doing in 1910? Of course not. But what was important were the new technologies developed in that year. So too, for every year. Without the technologies, there is no possibility of progress in our health.

Medvedik:

I think the ethical guidelines that can be worked on within this field (geroscience) should be applicable to all or most other medical interventions. I do not presently believe that the issues in clinical trials and therapeutics this field faces are qualitatively different from those of most other medical interventions. That said, I do believe that the development of useful and medically accepted cellular biomarkers of aging will be critical towards moving this field forward into clinical applications and accelerating the development of scientifically validated interventions that target the key drivers of the aging process.

Steele:

I think the guidelines should be pretty simple: anything that doesn’t have substantial human safety data shouldn’t be used outside of a trial setting. Untested therapies branded ‘longevity’ don’t advance the field – they pose a risk to its future progress.

The place I think it would be useful to develop guidelines is on how to aggregate data from therapies with solid safety data that are being taken off-label. The problem at the moment is that people taking drugs or other interventions in this way can’t accelerate progress because protocols and doses aren’t standardized, and data aren’t being collected centrally. If we can solve that problem, then it would be the time to debate which treatments would balance safety and accelerating the field.

Morgunov:

Yes – but they shouldn’t create regulatory monopolies like the FDA. We need a system of “quality stamps” from different independent regulators, ranging from the most stringent to the more flexible.

If you want only ultra-vetted products, choose the FDA stamp. If you’re willing to take more risk for a breakthrough, consider a different standard. Ideally, these regulators would also act as insurers, covering liability so patients are protected if something goes wrong. This would give people a real choice: maximum caution or a chance to give it a try today.

Editor’s note (Sept. 3, 2025): This story was updated to reflect additional information from RAADfest organizers and the Southern Nevada Health District.

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future.

Longevity investors

Countdown to the Longevity Investors Conference 2025

Longevity Investors, launched back in 2020 as the first industry event series fully focusing on investors, wants to educate investors and connect them to the leading key opinion leaders in the industry. The vision and ambition of Longevity Investors is to bring more capital into the longevity market. Beyond its flagship gatherings, Longevity Investors sustains dialogue through Longevity Investors News, keeping the community connected to the latest advancements year-round.

At the center of this mission stands the flagship Longevity Investors Conference 2025. From 22–25 September 2025, the sixth edition will take place at the five-star hotel Le Grand Bellevue in Gstaad, Switzerland – a discreet alpine setting that combines world-class luxury with the privacy essential for meaningful dialogue.Widely recognized as the most exclusive conference connecting high-level investors with leading scientists, thought leaders, and carefully selected startups in the longevity sector, the Longevity Investors Conference 2025 offers more than content. It delivers an immersive experience where science and capital meet in an intimate, highly curated environment. With the longevity sector projected to surpass $600 billion by 2026, the conference provides a rare opportunity to gain direct insight into one of the fastest-emerging investment markets of our time.

This year’s edition emphasizes depth of dialogue and high-value networking. The program is designed to foster meaningful conversations and trusted relationships, with closed-door roundtables, focused breakout discussions, and tailored one-on-one meetings supported by an enhanced matchmaking platform. Every exchange is carefully crafted to move beyond surface-level insights, giving participants direct access to the people and ideas driving longevity innovation.

Global Perspectives, Global Partnerships

The Longevity Investors Conference 2025 not only features an exceptional lineup of speakers — including Eric Verdin, Jamie Justice, Brad Stanfield, Matt Kaeberlein, Aubrey de Grey, Joe Betts-Lacroix, Sergey Young, David Gobel, Sheila Lirio Marcelo, João Pedro de Magalhães, and Garri Zmudze among other distinguished voices — it also brings together partners and sponsors from across the globe. From the United States and China to Saudi Arabia, Switzerland, and Europe, and with representation from Latin America, the conference reflects a truly international movement.

One of the Longevity Investors Conference’s most distinctive features is its speaker-to-attendee ratio. With roughly one speaker for every three to four participants, the ratio at the Longevity Investors Conference 2025 is unique in the industry. This ensures that conversations are not only possible but natural — with speakers fully present on-site, creating rare opportunities for candid discussions and genuine relationships.

Alongside its formal program, the Longevity Investors Conference 2025 offers a series of curated experiences designed to embody the principles of longevity and wellbeing. These include a sunset reception on the Mansard Rooftop terrace overlooking Gstaad, a cable-car ascent to Eggli Mountain for a traditional alpine lunch, and the return of the popular guided hike, combining restorative nature with opportunities for meaningful dialogue. On site, participants will also have access to innovative health and performance sessions such as red light therapy and full-body strength training and running sessions with THE UNIT — underscoring the belief that longevity should not only be discussed, but also lived.

The conference will culminate in an elegant gala dinner, featuring a tombola that reflects the spirit of innovation, longevity, and luxury. Prizes include a private flight over Gstaad with Haute Aviation, a year’s supply of AVEA’s patented Collagen Activator, a luxury night at Le Grand Bellevue, a wellbeing-focused cruise with BlueCruise, a lifetime cryopreservation membership from Tomorrow Bio, and a personalized peptide course from Symptomedica, with further rewards to be announced.

“We are building on the momentum of last year’s success and are committed to providing an even more impactful platform for fostering collaboration and driving investment in the longevity space,” says Marc P. Bernegger, Co-Founder of Longevity Investors.

His fellow Co-Founder Tobias Reichmuth adds: “The longevity sector is rapidly emerging as one of the most compelling investment themes of our time. Breakthroughs are happening at pace, and the Longevity Investors Conference provides the trusted setting where investors can engage with the leaders shaping this transformative space.”

Interested investors fulfilling the selection criteria can apply here to join the conversation shaping the future of human healthspan.

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future.
Rejuvenation Roundup August 2025

Rejuvenation Roundup August 2025

Over the last month, researchers have discovered how well-known substances can confer physical benefits, delivered compounds into the bloodstream in new ways, and continued to develop new forms of medicine. Here’s what’s happened in August.

Team and activities

Lifespan AllianceLifespan Alliance Launch & New Leadership at LRI: We have announced the launch of the Lifespan Alliance, a sponsorship initiative uniting mission-driven companies and visionary organizations dedicated to extending healthy human lifespan.

Interviews

Nir Barzilai: “Positive Evidence for Metformin is Mounting”: Dr. Nir Barzilai, the director of the Institute for Aging Research at the Albert Einstein College of Medicine, among his many other titles, is one of geroscience’s most prominent figures.

Research Roundup

Human brainStudy Finds Metformin’s Action Is Regulated by the Brain: A new study has shown that, unlike many other glucose-lowering drugs, metformin is regulated by the protein Ras1 in a specific subset of neurons, and when injected into the brain, even tiny doses of metformin can do the job.

A Brain Clock for Finding Rejuvenating Medications: Researchers have developed a transcription-based clock that estimates brain age and used it to identify potential interventions against age-related neurodegeneration.

Intestinal wallStudy Paves Road for Oral Delivery of Proteins: Using a pathogen-originated protein and a human antibody, scientists have created a chimeric construct that can deliver protein cargo via the intestine.

Nicotine Consumption Improves Motor Functions in Male Mice: A recent study reported that long-term nicotine consumption had a positive impact on motor function in male mice. The beneficial effects were mediated by sphingolipid and NAD+ metabolism.

Stem cellsA Better Extracellular Matrix Makes Aged Cells Act Youthful: Researchers have found that growing older cells in a youthful medium causes them to behave and function more like younger cells, suggesting a new method of creating stem cell-based therapies.

Mitochondria Transplant Improves Chemotherapy in Lung Cancer: Scientists have demonstrated that injecting healthy mitochondria either systematically or directly into the tumor microenvironment boosts the efficiency of a standard anti-cancer therapy.

Atrophied MusclesHow FGF21 Fights Back Against a Muscle-Wasting Disease: In Aging, researchers have reported on how an increase in FGF21, a myokine that encourages muscle growth, impacts the progression of amyotrophic lateral sclerosis.

Cannabis as a Treatment for Age-Related Diseases: Researchers have recently published a review on how cannabis use among older adults impacts age-related conditions and longevity.

Heart diseaseHow Inflammation Is Linked to Heart Disease: In Cell Reports Medicine, researchers have published a detailed review on the relationship between cardiovascular disease and the age-related inflammation known as inflammaging.

Moving to a More Walkable City Increases Step Count: Working with data from a smartphone app, scientists have shown for the first time that relocating to a more walkable city is linked to increased daily step counts.

Lab mouse on cageExosomes Reduce Sarcopenia in a Mouse Model: Researchers have discovered that exosomes secreted by mesenchymal stem cells derived from human umbilical cord tissue (hucMSC-Exos) restore muscle function in a mouse model of sarcopenia.

An Overly Youthful Immune System Might Cause Autoimmunity: Scientists have proposed a hypothesis that immune aging might be necessary to shield people from autoimmune effects, as the repertoire of autoantigens expands with age.

Lithium pillLow-Dose Lithium Reverses Features of Alzheimer’s in Mice: In a recent study, researchers identified the critical role that lithium plays in brain health and the development of mild cognitive impairment and Alzheimer’s disease.

Researchers Identify a Key Senescence-Spreading Factor: In Metabolism Clinical & Experimental, researchers have described how the reduced isoform of the SASP factor HMGB1 causes senescence to spread.

Exercise clockTransient Epigenetic Rejuvenation Recorded in Athletes: A new study has found that professional soccer players experience a drop in their biological age after a match, as measured by biomarkers assessed with state-of-the-art methylation clocks. We asked Dr. Steve Horvath, the study’s co-author, to comment.

Reducing an Iron-Associated Protein Fights Cognitive Decline: In Nature Aging, researchers have described how an increase in the iron-associated protein ferritin light chain 1 (FTL1) is related to age-related cognitive impairment.

Blood vessel in brainImpaired Brain Blood Flow Might Be Important in Alzheimer’s: Scientists have developed a potent diagnostic tool based on the vascular hypothesis for Alzheimer’s. It outperformed three current techniques and might offer clues to the mechanism behind the disease.

Rejuvenating Atherosclerotic Foam Cells: According to a study published by Cyclarity Therapeutics, its drug UDP-003 shows benefits in reversing the root cause of atherosclerotic plaques.

Wrapped DNALoose Chromatin, Senescent Inflammation, and Cancer: In Aging Cell, researchers have reported that chromatin demethylation allows SASP compounds to be more easily expressed.

Moderate Beer Consumption Produces Benefits in Mice: Scientists have given three types of beer to artificially aged male mice and recorded numerous beneficial effects, including improvements in microbiome diversity and lipid profiles.

Effects of fasting-mimicking diets with low and high protein content on cardiometabolic health and autophagy: A randomized, parallel group study: Both diets promoted cardiometabolic health and induction of autophagy, with the high-protein diet selectively conferring novel benefits in body composition, circulating lipid profiles, heart rate variability and gut microbiome health.

Lower diet quality accelerates DNA methylation-based age: These findings demonstrate the independent contribution of diet quality to healthy aging-related epigenetic mechanisms.

Effects of resistance-based training and polyphenol supplementation on physical function, metabolism, and inflammation in aging individuals: These results indicate that a combined RT and minimal HIIT program improves muscular, aerobic, and metabolic health, and may improve inflammatory regulation in aging adults.

Curcumin Induces Transgenerational and Sex-Specific Effects on Lifespan, Gene Expression, and Metabolism in the Fruit Fly Drosophila melanogaster: These results show that curcumin’s beneficial effects in the parental generation are followed by deleterious effects in the offspring.

Association of 25(OH)D serum level with biological aging: A Cross-Sectional Study of 2007–2016 NHANES surveys: These findings indicate that vitamin D insufficiency has an inverse link with accelerated biological aging, and high levels of vitamin D in males accelerated biological aging as well.

The novel effects of the cardiovascular drug ranolazine on the alleviation of age-related cognitive decline and the underlying mechanisms: This study reveals ranolazine’s previously unrecognized role in alleviating age-related cognitive decline for the first time.

What is the clinical evidence to support off-label rapamycin therapy in healthy adults?: Despite the preclinical evidence supporting the use of sirolimus to enhance mean and maximal lifespan, the data in humans have yet to establish that rapamycin, or its analogues, is a proven seno-therapeutic that can delay aging in healthy older adults.

The association between lutein and zeaxanthin intake and multi-level biological aging: These findings highlight lutein’s translatable potential for aging interventions and provide insights for dietary strategies in aging health management.

Statin Treatment for Reducing Mortality Risk in Individuals over 75 Years of Age: A Large-Scale Retrospective Analysis: Provision of statin therapy contributes to a reduction in risk of all-cause mortality in individuals aged 75 years and above who have an unknown history of cardiovascular disease, regardless of the type of statin or the patient’s CCI score.

No winners or losers: clinical chemistry-based biological aging metrics perform similarly across cohorts and health outcomes: Effect sizes are heterogeneous across cohorts, highlighting the importance of replicating findings in different contexts and with different metrics.

From clock to clock: Therapeutic target discovery for aging and age-related diseases: Building on recently published aging clocks, the researchers re-establish a significant proportion of known drug targets by identifying clock-associated genes, highlighting the potential of these clocks for target identification

A unifying theory of aging and mortality: This paper is the first to offer a full mathematical explanation of Gompertz’s law and its limitations based on network theory.

Identifying the optimal combinations of modifiable dementia risk factors to target in multidomain intervention: Identifying risk factor combinations with the highest prevalence and largest effect sizes can enhance efficiency of trial design.

Network Pharmacology and Machine Learning Identify Flavonoids as Potential Senotherapeutics: These researchers’ results enabled them to identify 714 compounds with potential senescent therapeutic activity, of which 270 exhibited desirable medicinal chemistry properties, and they developed an interactive web tool freely accessible to the scientific community.

Prevalent mesenchymal drift in aging and disease is reversed by partial reprogramming: These findings provide mechanistic insight into the underlying beneficial effects of partial reprogramming and offer a framework for developing interventions to reverse age-related diseases using the partial reprogramming approach.

Translational fidelity and longevity are genetically linked: These results support the impact of translational fidelity on intra-specific longevity variation.

News Nuggets

Human Augmentation SummitAugmentation Lab Announces the Human Augmentation Summit: On August 23, the 2025 Human Augmentation Summit was a gathering of creators – from innovative startups and global companies to independent researchers and artists – all shaping the future of the human condition.

BioAge Labs: First Person Dosed in Phase 1 BGE-102 Trial: BioAge Labs, Inc., a clinical-stage biotechnology company developing therapeutic product candidates for metabolic diseases by targeting the biology of human aging, today announced that the first participant has been dosed in a Phase 1 clinical trial evaluating BGE-102.

Coming Up

Revive MERevive ME to Spotlight Healthy Longevity in Abu Dhabi: On November 26-27, Abu Dhabi is set to host the Middle East’s first-of-its-kind conference and exhibition dedicated to longevity science, biotechnology, regenerative medicine, ultra-personalised wellness, and AI-powered healthcare innovation, Revive ME.

2025 Asian Pacific Longevity Medicine International Summit: On October 4-5, the Asia-Pacific Longevity Society will host the inaugural Asian Pacific Longevity Medicine International Summit (APAC-LMIS) at the SkyCity Marriott Hotel in Hong Kong, in partnership with several leading international longevity organizations.

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future.

Moderate Beer Consumption Produces Benefits in Mice

Scientists have given three types of beer to artificially aged male mice and recorded numerous beneficial effects, including improvements in microbiome diversity and lipid profiles [1].

Can alcohol be healthy?

While it is firmly established that excessive alcohol consumption negatively impacts health, debates around moderate consumption are still ongoing. Some researchers suggest that the healthy level of alcohol consumption is zero [2], while others claim that the benefits outweigh the risks [3]. To complicate things further, alcohol comes in many forms, and the type seems to matter a lot. This is not surprising, since alcoholic beverages are made from plants, which contain many biologically active substances.

A lot of our knowledge about the effects of alcohol on human health comes from epidemiological studies, which can only establish correlations between levels of consumption and health outcomes and not causal relationships. Such studies are notoriously noisy and unreliable and cannot provide insight into the mechanisms of action.

A team of Chinese researchers from Qingdao Marine Biomedical Research Institute and the State Key Laboratory of Biological Fermentation Engineering of Beer at Tsingtao Brewery (note the industry connection) set out to close some of those gaps by getting mice drunk. To be precise, the animals were given small doses of beer roughly equivalent to 700 milliliters per week for humans.

To study the effects of the beverage on an aged organism, the mice were treated with D-galactose, a compound that induces aging-like phenotypes via increased production of reactive oxygen species and advanced glycation end products (AGEs), which quickly leads to weaker antioxidant defenses, liver/kidney strain, and a disrupted gut microbiome.

For four weeks, the artificially aged mice were given one of the three types of beer that the researchers obtained from the Tsingtao Brewery lab: original, IPA, and stout. The first one was basically an unfiltered pale lager, 5.42% alcohol by volume (ABV). The IPA and the stout packed a bit more punch: 5.83% and 7.54%, respectively.

All three beers mitigated the oxidative stress induced by D-galactose. Stout showed the strongest antioxidant effect overall, increasing the levels of the antioxidant enzymes superoxide dismutase (SOD) and catalase and lowering malondialdehyde (MDA), a marker of oxidative damage to fats in membranes (lipid peroxidation). Original beer most clearly improved glutathione peroxidase (GSH-Px), the cell’s primary antioxidant.

All three beers also produced anti-inflammatory effects. The levels of the pro-inflammatory cytokine IL-6 were reduced by IPA and stout. Original and stout lowered the levels of another pro-inflammatory cytokine, IL-15. Finally, tumor necrosis factor alpha (TNF-α), another marker of inflammation, was notably reduced by IPA. The researchers, however, suggest that the anti-inflammatory effects might be downstream from the antioxidative ones.

The team went on to study kidney and liver function and histology. Alcohol is usually associated with liver damage, but in this study, beer actually improved things in the liver compared to artificially aged controls. Stout led to lower levels of the liver markers ALT and AKP (also known as ALP), IPA lowered only AKP, and the original beer reduced AST levels. All the beers rescued liver damage caused by D-galactose, although the original beer’s effect was the smallest among the three. Kidney injury from D-galactose was attenuated by all beers as well.

Just like natural aging, D-galactose caused the mice’s lipid profiles to worsen (dyslipidemia). Here, too, beer seemed to help. IPA shined by lowering the levels of harmful LDL cholesterol, total cholesterol, and triglycerides. Original and stout lowered both LDL and total cholesterol but did not significantly impact triglycerides.

Beer effects

Microbiome improvements

The researchers thoroughly explored the impact of beer on the microbiome. D-galactose decreased gut diversity and skewed the microbiome. Beer reversed many of these changes: diversity rebounded, as beneficial bacteria that produce short-chain fatty acids (Roseburia, Lactobacillus, Odoribacte) increased in numbers while potentially pro-inflammatory taxa (e.g., Colidextribacter) declined.

The unfiltered original beer showed the biggest diversity bump, IPA demonstrated the clearest rebalancing, and stout most strengthened Lactobacillus/SCFA producers. These shifts tracked with lower inflammatory signals and better antioxidant and lipid markers.

The researchers tentatively attribute the effects they discovered to various bioactive molecules in the three beers. For example, the unfiltered original beer might be more effective in restoring microbiome diversity due to the high content of live yeast. Stout performed best as an antioxidant and hepatoprotector, consistent with its higher polyphenol and melanoidin content from roasted malts. Finally, IPA excelled in anti-inflammation and lipid regulation, which may be attributed to the activity of bitter acids abundant in hops.

The study had several limitations, such as using only male mice, as aging processes and responses to therapies often differ by sex. Importantly, the researchers used an artificial model of aging in otherwise young mice, which obviously does not fully recapitulate natural aging in humans. Finally, due to its short duration, the study may be less relevant for lifelong consumption.

On the other hand, using three types of beers with different effects is a nice touch. The authors call for other researchers to adopt this approach due to the notable diversity within different types of alcohol (beer, wine, strong spirits).

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future.

Literature

[1] Fu, X., Wang, C., Yang, Z., Yu, J., Wang, J., Cao, W., … & Hou, H. (2025). Moderate Beer Consumption Ameliorated Aging‐Related Metabolic Disorders Induced by D‐Galactose in Mice via Modulating Gut Microbiota Dysbiosis. Food Science & Nutrition, 13(8), e70678.

[2] Griswold, M. G., Fullman, N., Hawley, C., Arian, N., Zimsen, S. R., Tymeson, H. D., … & Farioli, A. (2018). Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet, 392(10152), 1015-1035.

[3] Meister, K. A., Whelan, E. M., & Kava, R. (2000). The health effects of moderate alcohol intake in humans: an epidemiologic review. Critical Reviews in Clinical Laboratory Sciences, 37(3), 261-296.

Asian Pacific Longevity Summit

2025 Asian Pacific Longevity Medicine International Summit

Longevity medicine is rapidly emerging as a credible, fast-growing discipline in modern healthcare, powered by rigorous science and significant global investment. On October 4–5, 2025, the Asia-Pacific Longevity Society will host the inaugural Asian Pacific Longevity Medicine International Summit (APAC-LMIS) at the SkyCity Marriott Hotel in Hong Kong, in partnership with several leading international longevity organizations.

This landmark gathering will bring together leading scientists, clinicians, biotech startups, and venture investors not only from Asia-Pacific countries, but also from around the world, to translate cutting-edge longevity research into ethical, evidence-based clinical practice across both longevity clinics and mainstream hospital settings.

In an era when online “biohacking” trends and commercially driven claims can overshadow genuine geroscience, APAC-LMIS sets itself apart by focusing exclusively on peer-reviewed research and proven approaches. As the co-organizers note:

“We’re cutting through the noise and putting credible, data-driven professional education directly into the hands of physicians and healthcare providers. Our aim is to cultivate well-trained longevity doctors who can deliver safe, effective care that truly benefits patients.”

Our mission: Live Longer, Live Healthier, Embrace the Best Lifestyle.

Why APAC-LMIS is Unique:

  1. First in APAC: Over 30 countries represented, covering 53% of the world’s population, including super-aging societies such as Japan, Hong Kong, and Singapore.
  2. Science-Based Solutions: Strong engagement from physician-scientists.
  3. Training Programs: Intensive courses for healthcare providers and physicians.
  4. Best Practices: Showcasing successful longevity clinic and healthy longevity center models across public and private sectors.
  5. Living Lab: Testing and validating non-medical longevity and wellbeing solutions.
  6. Top 10 Longevity Breakthrough Awards: Advisory committee highlights the most promising innovations for clinical and home use.

The Summit’s goal is clear: to establish standards, uphold scientific rigor, and solidify longevity medicine as a trusted medical specialty—not a fleeting trend. This Summit marks the beginning of an ongoing series of international meetings designed to shape the future of medicine and improve healthspan globally.

We warmly invite you to join us in Hong Kong this October to take part in this vital conversation and help advance the global practice of longevity medicine.

Official sites: https://www.apaclongevitysociety.org and https://longevityawards.org/

Media and partnership inquiries

For press credentials, sponsorship opportunities, speaking proposals, and delegate registration, please contact the APAC-LMIS organizing committee at Admin@GlobalMD.org