New Study Raises Questions About The Anti-Aging Benefits Of Blood Transfusions

Date Posted: February 3, 2017

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New Study Raises Questions About The Anti-Aging Benefits Of Blood Transfusions

There has been a lot of interest in the idea that young blood transfused into an old person could be a way to regenerate tissues and reverse some of the damage caused by the aging process.

Today a brand new podcast with Doctors Irina and Michael Conboy was brought to our attention, and we could not resist a little commentary. So, what started all this interest in young blood and its potential to reverse some of the aging process? It all started with the early parabiosis experiments, where the circulatory systems of two mice were joined together, linking young and old animals together.

This sharing of systems saw some measure of rejuvenation in the aged animals, leading some to think that it was something in the blood of the young animal that was reversing some of the damage aging does. Since then, the media has been filled with stories of vampires, Countess Báthory, and fears of young people being harvested for blood. Of course, as is often the case, the actual science and interpretation by the media are worlds apart.

The search for the secret sauce

A significant number of researchers have also been engaged in hunting for the elusive “secret sauce” that some believe is present in young blood; however, new research suggests that they might be barking up the wrong tree, and that the answer may be closer to home. Irina and Michael have studied stem cells and intercellular communication and its relation to aging.

They were some of the original researchers who worked on parabiosis and noticed this rejuvenation effect when animals were joined, but since those early days they have taken a different path to many researchers who are busy sifting young blood for those elusive pro-youthful factors. They have in that time successfully identified a number of pro-aging molecules in aged blood which are responsible for the decline of tissue repair and the increased levels of inflammation aging causes[1-2].

This was further supported by the work of Villeda, who identified B2M as another pro-aging factor in aged blood[3]. Now their recent research suggests that it is not what is in young blood that counts, but what you remove from old blood that is the key to rejuvenating old and damaged tissues[4]. In other words, the effects of young blood interpreted as being the reason for rejuvenation may instead be the dilution of these pro-aging factors in old blood.

This is further reinforced by another researcher who recently announced they had isolated VCAM1, yet another pro-aging factor in old blood. This may also explain why subsequent transfusions with mice failed to produce the same noteworthy effects that parabiosis did, as they did not share a joined circulatory system[5].

Whilst we will hopefully learn something useful from the current human studies using young blood transfusions, any benefit could potentially be explained by this dilution effect. Irina Conboy has strongly criticized the “young blood” studies as premature, given the early stage of scientific research. “I don’t think that there is any scientific justification that it would work,” she said to MIT Technology Review. “Taking a young person’s blood and infusing it into an old person is not medicine.”

Conclusion

Of course we have a long way to go before all these questions can be answered fully, and these clinical trials with humans may yet turn up new information as will the subsequent follow up studies by the Conboys. However, those questions aside, the logistics involved mean that regular transfusions of young blood are unlikely to be a practical solution for a population-wide therapy to address the aging process.

Literature

[1] Elabd, C., Cousin, W., Upadhyayula, P., Chen, R. Y., Chooljian, M. S., Li, J., … & Conboy, I. M. (2014). Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration. Nature communications, 5. [2] Yousef, H., Conboy, M. J., Morgenthaler, A., Schlesinger, C., Bugaj, L., Paliwal, P., … & Schaffer, D. (2015). Systemic attenuation of the TGF-β pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal. Oncotarget, 6(14), 11959. [3] Smith, L. K., He, Y., Park, J. S., Bieri, G., Snethlage, C. E., Lin, K., … & Wheatley, E. G. (2015). [beta] 2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis. Nature medicine, 21(8), 932-937. [4] Rebo, J., Mehdipour, M., Gathwala, R., Causey, K., Liu, Y., Conboy, M. J., & Conboy, I. M. (2016). A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood. Nature Communications, 7. [5] Shytikov, D., Balva, O., Debonneuil, E., Glukhovskiy, P., & Pishel, I. (2014). Aged mice repeatedly injected with plasma from young mice: a survival study. BioResearch open access, 3(5), 226-232.

Date Posted: January 20, 2017

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Intrinsic Resistance to the Idea of Life Extension or Wrong Messaging?

Most advocates of life extension report facing resistance to the idea of increased lifespans by medical means when trying to disseminate it among the general public. Resistance manifests itself in many forms, ranging from concerns such as overpopulation to concerns about unequal access to life-extending treatments.

However, the most unexpected thing is probably that people often don’t want an increased lifespan at all. Surveys in different countries show that when people are asked “how long would you like to live?”, they often give a number equal to or slightly higher than the current life expectancy in a given country [1-4].

Wait, isn’t extending life by decades something that everyone should strive for? Why do we often see a lack of enthusiasm for the idea in general?

It’s not what you say; it’s how you say it

It turns out that the reaction of general public to the idea depends on how the message is formulated. When only life extension is offered, without any details of how healthy, mentally sound, and good-looking an individual could become, people express less support for the idea.

However, when life extension is proposed as a combination of perfect physical and mental health, it changes the response dramatically, leading to many more people accepting the idea and showing support for the development of corresponding medical technologies.

Here is some relevant data from a recent study.

We surveyed 1000 individuals (through “Ask Your Target Market”) about how long they wished to live (to age 85, 120, 150, or indefinitely), under 3 scenarios: (1) sustained mental and physical youthfulness, (2) mental youthfulness only, (3) physical youthfulness only. While responses to the two partial youthfulness conditions recapitulated the results of previous surveys (Cicirelli, 2011; Kogan et al., 2011; Partridge et al., 2011; Duncan, 2012; Pew Research Center, 2013), i.e., most responders (65.3%) wished to live to age 85 only—under scenario (1) the pattern of responses was completely different. When guaranteed mental and physical health, 797 of 1000 people wanted to live to 120 or longer, and 53.1% of the 797 desired unlimited life spans. Furthermore, 70.1% of the people who responded 85 to scenario (2) or (3) changed their answer to 120 or longer in scenario (1). The full survey response data is publicly available here.

It is important to note that researchers have also reported other factors that increase support for life extension and related medical innovations. An interest in science, for example, appears to be the strongest predictor of a positive attitude towards medical interventions to extend life.

The fraction of people who changed their answer from 85 to 120 or longer was significantly higher among people with some interest in science (445/622 vs. 13/31, p < 0.001, Fisher’s exact test), and this was the main predictor of changing the answer to favor longer life. Less significant correlations were found with other surveyed variables such as age, health status, and self-esteem. Similar results were recently reported for Canadians (Dragojlovic, 2013): 59% of 1231 respondents wished to live to 120 (the maximum age included in that survey), and science orientation was the strongest predictor of support for life extension.

In surveys in which the message did not include a promise of perfect health combined with longevity, males were found to be more likely to support life extension than females [5]. Most likely, this can be explained by different perceptions of risk.

Males are found to be more likely to take risks [6], including the risks involved in using an innovative technology of which the long-term effects are still unknown and the actual benefits are not clear.

In other studies, however, when healthy life extension (with a “utopian” scenario) was offered, this difference between the sexes did not remain consistent [7]; males and females were equally supportive of life extension technologies.

It could be that a positive scenario does not engage the mechanisms of risk avoidance. However, it means that solely by adding perfect health to life extension in our messages, we can significantly widen the number of our supporters.

Conclusion

Studies like this illustrate the importance of analyzing how the nature of the message matters in furthering our cause.

The advocates of rejuvenation biotechnology, including research groups and fundraisers for biological aging research, should carefully consider the messages they are using, as some of them are more efficient at encouraging an informed and engaging discussion with society about the benefits of bringing aging under medical control.

This subject feeds into the bottlenecks we currently have in research, and you can read more about that here.

Literature [1] Lang, F. R., Baltes, P. B., & Wagner, G. G. (2007). Desired lifetime and end-of-life desires across adulthood from 20 to 90: A dual-source information model. The Journals of Gerontology Series B: Psychological Sciences and Social Sciences, 62(5), P268-P276. [2] Lugo, L., Cooperman, A., & Funk, C. (2013). Living to 120 and Beyond: Americans’ Views on Aging, Medical Advances, and Radical Life Extension. Pew Research Center, August, 6. URL: https://www.pewforum.org/2013/08/06/living-to-120-and-beyond-americans-views-on-aging-medical-advances-and-radical-life-extension/ [3] CARP Radical Life Extension Poll Report (2013). URL: https://www.carp.ca/wp-content/uploads/2013/09/Life-Extension-Poll-Report.pdf [4] Financial University of the Government of the Russian Federation, Sociology Faculty (2015). Most of Russians want to live up to 80 years only. (Bol’shinstvo rossijan hochet dozhit’ tol’ko do 80 let). URL: https://www.fa.ru/chair/priklsoc/Documents/24_Life_Expectancy_2015.pdf [5] Partridge, B., Lucke, J., Bartlett, H., & Hall, W. (2011). Public attitudes towards human life extension by intervening in ageing. Journal of Aging Studies, 25(2), 73-83. [6] Harris, C. R., Jenkins, M., & Glaser, D. (2006). Gender differences in risk assessment: why do women take fewer risks than men?. Judgment and Decision making, 1(1), 48. [7] Kogan, N., Tucker, J., & Porter, M. (2011). Extending the human life span: an exploratory study of pro-and anti-longevity attitudes. The International Journal of Aging and Human Development, 73(1), 1-25.

Date Posted: January 18, 2017

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The Fountain of Youth Could Be Closer to Hand Than We Thought

There has been a lot of hype and hope over transfusing old people with young blood in an attempt to rejuvenate the body in a similar manner to earlier heterochronic parabiosis experiments, in which the circulatory systems of an old and a young mouse were linked and some level of rejuvenation was observed [1].

Many researchers initially thought that the positive results in these tests were due to there being pro-youthful signals in the young blood. However, more recent research suggests that the possible reason is the dilution of pro-aging factors present in the old blood rather than there being any “secret sauce” in young blood.

Indeed, various studies have shown that pro-aging factors already present in the aged blood are responsible for loss of tissue regeneration and stem cell function, and inhibiting or removing these factors has induced some level of tissue regeneration [2, 3] and cognitive improvement [4]. This has lead some to search for the special ingredient in young blood that was causing the rejuvenating effect, but the solution may be even simpler.

We might be able to filter aged blood

Recent research suggests that it isn’t what you put in that makes the difference; it’s what you remove that counts [5]. Indeed, the team led by Irina Conboy at UC Berkeley is now working on a device that can filter out high levels of pro-aging signals from old human blood and resetting them to more youthful levels.

In The Guardian, Irina Conboy said:

If you can remove key inhibitor molecules from the blood of an old person and then return that blood into them, that could be immediately therapeutic. We are developing ideas for clinical trials to see what happens if you normalize levels of one key protein we think is inhibitory. We hope to start in six months and have results in three years. Right now our health declines after about seven decades. We are pretty much hoping to extend the productive plateau, where you’re not necessarily the world champion in swimming or running marathons, but you can continue for a few more decades without any critical illnesses.

Adding further weight to the dilution effect, recently, Hanadie Yousef at Stanford University in California, who has worked with Irina Conboy in the past, seems to have identified a protein that is causing some of the damage and has developed a way to block it.

The effects of blood on ageing were first discovered in experiments that stitched young and old mice together so that they shared circulating blood. Older mice seem to benefit from such an arrangement, developing healthier organs and becoming protected from age-related disease. But young mice aged prematurely. Such experiments suggest that, while young blood can be restorative, there is something in old blood that is actively harmful. Now researchers seem to have identified a protein that is causing some of the damage, and have developed a way to block it. The researchers found that the amount of a protein called VCAM1 in the blood increases with age. In people over the age of 65, the levels of this protein are 30 per cent higher than in under-25s. To test the effect of VCAM1, researchers injected young mice with blood plasma taken from older mice. Sure enough, they showed signs of ageing: more inflammation in the brain, and fewer new brain cells being generated, which happens in a process called neurogenesis. Blood plasma from old people had the same effect on mice. When researchers injected plasma from people in their late 60s into the bodies of 3-month-old mice – about 20 years in human terms – the mice’s brains showed signs of ageing. These effects were prevented when researchers injected a compound that blocks VCAM1. When the mice were given this antibody before or at the same time as old blood, they were protected from its harmful effects. Some teams have begun giving plasma from young donors to older people, to see if it can improve their health, or even reduce the effect of Alzheimer’s disease. But for the best chances of success, we’ll also need to neutralise the damaging effects of old blood. Other researchers comment that it is “surprising that a single protein seems to have such a huge effect,” but the results need to be replicated by another lab. A drug that protects people from the effects of old blood would be preferable to plasma injections. Should transfusions from young donors turn out to be effective, it would be difficult to scale this up as a treatment for all. Drugs that block harmful proteins in our own blood would be cheaper, safer and more accessible. Source: Newscientist

Conclusion

It seems that filtering out pro-aging factors might be the optimal approach here, and, hopefully, Irina Conboy will get the results we are hoping for, opening up the door for true rejuvenation of aged tissues.

Literature

[1] Conboy, I. M., & Rando, T. A. (2012). Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches. Cell Cycle, 11(12), 2260-2267.

[2} Conboy, I. M., Conboy, M. J., Wagers, A. J., Girma, E. R., Weissman, I. L., & Rando, T. A. (2005). Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature, 433(7027), 760-764.

[3] Yousef, H., Conboy, M. J., Morgenthaler, A., Schlesinger, C., Bugaj, L., Paliwal, P., … & Schaffer, D. (2015). Systemic attenuation of the TGF-β pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal. Oncotarget, 6(14), 11959.

[4] Smith, L. K., He, Y., Park, J. S., Bieri, G., Snethlage, C. E., Lin, K., … & Wheatley, E. G. (2015). [beta] 2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis. Nature medicine, 21(8), 932-937.

[5] Rebo, J., Mehdipour, M., Gathwala, R., Causey, K., Liu, Y., Conboy, M. J., & Conboy, I. M. (2016). A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood. Nature Communications, 7.

Date Posted: January 16, 2017

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Trust me, I’m a “Biologist” joins forces with LEAF

We are very pleased to announce that Trust me, I’m a “Biologist”, a popular science and biology page, has joined the Lifespan Network, a group of like-minded groups and organizations working in science.

With a community of over 739,000 readers, this is a very popular science page on Facebook, and it publishes science memes and motivationals designed to encourage support for science by using humor.

If you use Facebook and enjoy science and geeky humor, we highly recommend checking out the page and throwing it a like. We must warn you that we are not responsible for the amount of time you might spend laughing at the jokes.

We believe that science can create a brighter future and that, by supporting public engagement with science, we can all contribute to making a better world; thus, we consider the goal of Trust me, I’m a “Biologist” to be compatible with ours and are pleased to collaborate with this group to support this goal.

Conclusion

As part of our commitment to the ethical progress of medical science, LEAF promotes scientific research and learning via our crowdfunding website Lifespan.io and our educational hub at the LEAF website.

We will be expanding our articles and resources in the coming year and taking steps to engage people even more with science and getting them excited about the possibilities that the future holds.

Date Posted: January 14, 2017

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Dr. Aubrey de Grey – Reimagine Aging

For many of you reading this article, Dr. Aubrey de Grey needs little or no introduction. However, for those less well acquainted with his work, he is one of the most prominent scientists in the field of rejuvenation biotechnology.

More than fifteen years ago, Aubrey took up the challenge of persuading the aging research community that aging was something in which medical science could and should intervene. Aubrey discovered plenty of evidence to show that aging is caused by seven broad damage categories, which he has termed the seven deadly things.

Yet, that evidence was mostly ignored by the research community at the time, while scientific discussion about the treatment of aging in public could risk a loss of funding and even end a researcher’s career, and the vast majority of aging research was nothing more than a process of gathering data.

No longer a taboo

However, thanks to iconoclasts like Dr. de Grey, this situation has changed over the last few years. Discussions among researchers are now concerned with how aging can be treated, not if it can be treated.

Public discussion of the subject is no longer a seen as a taboo that can cause loss of funding or a career. Numerous peer reviewed scientific publications openly explore aging and discuss ideas about possible interventions that a mere decade ago were dismissed as impossible.

This radical change was to a great extent due to the work of scientists, such as Aubrey, and the efforts of advocates within the community who have patiently worked to change the popular view, steering the conversation towards considering aging as something we can do something about.

Aubrey created and leads the SENS Research Foundation, an organization that, along with its parent non-profit foundation Methuselah, has helped move the goal of rejuvenation technology closer to being a reality.

The tide is turning

Many years ago, Aubrey proposed that removing senescent cells could be an approach to treating aging. This idea was dismissed by many people in the research community only a decade ago, despite the evidence that senescent cells played a key role in aging.

Now, this has changed, and therapies to clear senescent cells from old tissues have been demonstrated to improve health and even increase lifespan in mouse studies, and three biotech companies, Unity Biotechnology, Oisin Biotechnologies and Cellage, are working on bringing these treatments to the clinic.

In addition to these groups, Major Mouse Testing Program is also conducting research in the field, thanks to successful community fundraising last year on Lifespan.io, and is exploring the effects of senolytics on stem cell populations.

Dr. de Grey is often accused of encouraging fanciful ideas about living forever and immortality, something that dogs his every step and has for the last decade or more. In fact, Aubrey is far more grounded in reality and actual science. He is not a fan of the word “immortality”, because it gives a completely wrong idea about the field of rejuvenation biotechnology and its aims, as he explains:

“The first thing I want to do is get rid of the use of this word ‘immortality’, because it’s enormously damaging, it is not just wrong, it is damaging. It means zero risk of death from any cause—whereas I just work on one particular cause of death, namely aging. It is also a distraction; it causes people to think this whole quest is morally ambiguous and technologically fanciful.”

Conclusion

The world of medicine is changing, and while it has been an uphill battle to bring about a change in how we view and treat age-related diseases, the tide has finally began to turn, and we should remember the contribution that trailblazers such as Dr. Aubrey de Grey have made for scientific progress.

Date Posted: January 13, 2017

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New Therapy Could Make Chemotherapy Safer

Recently, there has been a focus on the removal of senescent cells as a therapy to treat age-related diseases by directly addressing one of the hallmarks of aging: senescent cell accumulation.

These senolytic therapies are the first SENS therapies to be developed in order to directly address and repair the damage that aging does to the body. We see the potential for this new kind of therapy in the research data, and evidence that senescent cells contribute to atherosclerosis [1], osteoporosis [2, 3], and many more age-related diseases continues to mount up.

A new research paper hot off the press shows another connection that, in retrospect, should have been obvious: the connection between cellular senescence, cancer [4], and the side effects of chemotherapy [5].

Chemotherapy is extremely toxic and damages and deregulates a number of cellular functions in the body. Chemotherapy works by inducing cancer cells to become senescent, but this process also causes a great deal of collateral damage that stresses healthy cells and causes a significant number of them to become senescent as well.

The immune system then removes these senescent cells and the debris, but some senescent cells resist this process and remain in situ. These populations of senescent cells accumulate naturally as part of the aging process anyway, causing inflammation, deregulation of intracellular signalling, and decline of tissue regeneration. In a very real sense, a course of chemotherapy could be considered to accelerate this particular aspect of aging.

Senescent cells do not divide or support the tissues of which they are part; instead, they emit a range of potentially harmful chemical signals, which encourage other nearby cells to also enter the same senescent state. Their presence causes many problems: they degrade tissue function, increase levels of chronic inflammation, and can increase the risk of cancer, as this latest paper discusses.

Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse
Abstract
Cellular senescence suppresses cancer by irreversibly arresting cell proliferation. Senescent cells acquire a pro-inflammatory senescence-associated secretory phenotype. Many genotoxic chemotherapies target proliferating cells non-specifically, often with adverse reactions. In accord with prior work, we show that several chemotherapeutic drugs induce senescence of primary murine and human cells. Using a transgenic mouse that permits tracking and eliminating senescent cells, we show that therapy-induced senescent (TIS) cells persist and contribute to local and systemic inflammation.
Eliminating TIS cells reduced several short- and long-term effects of the drugs, including bone marrow suppression, cardiac dysfunction, cancer recurrence and physical activity and strength. Consistent with our findings in mice, the risk of chemotherapy-induced fatigue was significantly greater in humans with increased expression of a senescence marker in T-cells prior to chemotherapy. These findings suggest that senescent cells can cause certain chemotherapy side effects, providing a new target to reduce the toxicity of anti-cancer treatments.

Conclusion

Based on this research, it appears that chemotherapy causes the rapid accumulation of senescent cells, and, in the long run, is bad for the patient due to driving this aging process and its associated risks. However, until better alternatives such as immunotherapy arrive, senolytic therapies could help to reduce the negative impact of chemotherapy.

Literature

[1] Childs, B. G., Baker, D. J., Wijshake, T., Conover, C. A., Campisi, J., & van Deursen, J. M. (2016). Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science, 354(6311), 472-477.

[2] Farr, J. N., Fraser, D. G., Wang, H., Jaehn, K., Ogrodnik, M. B., Weivoda, M. M., … & Bonewald, L. F. (2016). Identification of senescent cells in the bone microenvironment. Journal of Bone and Mineral Research, 31(11), 1920-1929.

[3] Xu, M., Bradley, E. W., Weivoda, M. M., Hwang, S. M., Pirtskhalava, T., Decklever, T., … & Lowe, V. (2016). Transplanted senescent cells induce an osteoarthritis-like condition in mice. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, glw154.

[4] Coppé, J. P., Desprez, P. Y., Krtolica, A., & Campisi, J. (2010). The senescence-associated secretory phenotype: the dark side of tumor suppression. Annual review of pathology, 5, 99.

[5] Demaria, M., O’Leary, M. N., Chang, J., Shao, L., Liu, S., Alimirah, F., … & Alston, S. (2016). Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse. Cancer Discovery, CD-16.a

Date Posted: January 10, 2017

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Synthetic biology could combat the aging process

Over the past few weeks, CellAge has been producing a number of video shorts to answer questions about its current fundraising campaign on Lifespan.io, so we have compiled them here in a single digest.

Its project aims to develop synthetic biology tools for detection and removal of toxic senescent cells that accumulate with time, causing inflammation and promoting age-related diseases. The removal of these cells has been a recent prominent focus of research in the aging field.

Are you a for-profit company?

“Yes. The reason why we are a for-profit is that it would be extremely hard to raise the funds needed to develop such tools and therapies otherwise (preclinical and clinical trials etc.). Like it or not, investors are looking for return on their investment, and this is the main source of money for most translational research.

For example, initiatives like SENS help develop technologies to a proof of concept stage, but after that, these technologies still need to be spun-out into for-profit companies; further development requires an injection of a lot of capital, and that usually comes only from investors who are looking for profit.

That being said, we will be making our first tools to target senescent cells available free of charge to researchers to help the entire field have access to a new aging biomarker and speed up progress.”

Is it safe to remove senescent cells?

“It depends how you remove these cells. You definitely do not want to stop cells from being able to become senescent, for example, because this ability helps wound healing and stopping cells from turning cancerous. Periodically removing these cells, however, could allow us to enjoy the positive benefits while also avoiding the negative aspects of having senescent cells in the tissues long-term, such as inflammation and contributing to age-related diseases.

Like all things, it is a question of balance, and we would have to carefully monitor how many and how quickly we remove senescent cells in order to fine-tune the process. Increasing amounts of research data shows that the benefits of removing these non-dividing cells are positive for health and longevity, and the hope now is that these results will translate to humans. Given the tests on mice and human cell lines, there is good reason to be positive about this potential.”

Can your technology be used to treat other SENS damages?

“I do believe it can! Synthetic biology is a broad field, but, in this case, we are talking about computing within the cell, potentially targeting many aspects of biology for potential modification.

I believe this approach can actually address all aspects of SENS (and this is why I have chosen to do synthetic biology), as you are basically creating new commands within the cell.

So, just imagine a situation where, for example, you create a synthetic circuit which senses different biomarkers within the cell, and if correct markers become present, the cell is removed (OncoSENS and ApoptoSENS) or is forced to perform asymmetric division to remove some junk (LysoSENS and MitoSENS) and so on. So yes, I believe there is promising and bright future for both synthetic biology and ageing research.”

Are senescent macrophages the problem?

“Only time and research will show if these senescent associated macrophages are the key cells that we should be aiming to destroy, and it might be so, but I think all senescent cells play a critical role in lowering the regenerative capacity of tissues.

It might indeed be the case, however, that only senescent macrophages need to be targeted, and that is where our technology has potential. If you use small molecules or generic promoters, such as p16, it might be very hard (if not practically impossible) to remove only the senescent macrophages, and that kind of specificity is something our system could help with.

The synthetic promoters that we will construct will be customized based on the input of cell types that we have, so if we use senescent fibroblasts, we will compile a sequence which only targets senescent fibroblasts. However, if we use senescent macrophages in our screen, the same is true. Bascially, we could customize the synthetic program to be selective and remove certain cell types only if needed.”

When will we see results from your research?

“For the development of our senescent cell detection system called SeneSENSE, we could see this arrive as soon as Q4 2017. The SeneSENSE system will be given freely to researchers in a bid to speed up progress in the field, and it will help with applications like identifying new senolytic candidates, assessing biological age, and confirming efficacy of senescent cell removal therapies.

Following this in Q4 2018, our stem cell quality control system would be introduced, allowing increased quality for stem cell transplants by accurately spotting senescent cells and allowing them to be removed prior to transplant.

Based on the current timeframes in research, we could see pre-clinical testing by 2019 with first application of our SeneHEALTH senescent cell therapy by 2028.”

Date Posted: December 10, 2016

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Promoting Your Right to Health on Human Rights Day

December 10th has been proclaimed Human Rights Day by the United Nations. Around 70 years ago, in 1948, the United Nations Assembly adopted the Universal Declaration of Human Rights, opening a new page in human history. The Declaration represents a standard of how human beings should be treated and how their rights and freedoms should be protected from any violation.

It is important for the longevity community to be familiar with the Articles of the Declaration related to healthcare and scientific progress. Knowing one’s rights and freedoms is necessary to engage in public discussion about bringing the aging process under medical control, spreading rejuvenation technologies worldwide, and making them affordable to everyone. Here are some useful citations.

Article 2

Everyone is entitled to all the rights and freedoms set forth in this Declaration, without distinction of any kind, such as race, colour, sex, language, religion, political or other opinion, national or social origin, property, birth or other status. Furthermore, no distinction shall be made on the basis of the political, jurisdictional or international status of the country or territory to which a person belongs, whether it be independent, trust, non-self-governing or under any other limitation of sovereignty.

Article 25

Everyone has the right to a standard of living adequate for the health and well-being of himself and of his family, including food, clothing, housing and medical care and necessary social services, and the right to security in the event of unemployment, sickness, disability, widowhood, old age or other lack of livelihood in circumstances beyond his control.
Motherhood and childhood are entitled to special care and assistance. All children, whether born in or out of wedlock, shall enjoy the same social protection.

Article 27

Everyone has the right freely to participate in the cultural life of the community, to enjoy the arts and to share in scientific advancement and its benefits.
Everyone has the right to the protection of the moral and material interests resulting from any scientific, literary or artistic production of which he is the author.

These principles apply to the activities of all UN bodies, including the World Health Organization (WHO). However, each body has its own constitution, where some rights, freedoms and responsibilities can be described in more detail. Hence, the constitution of the WHO provides more details on what exactly health is and the exact duties of this organization concerning the improvement of health in all nations. Here are some examples.

Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.

The enjoyment of the highest attainable standard of health is one of the fundamental rights of every human being without distinction of race, religion, political belief, economic or social condition.

The extension to all peoples of the benefits of medical, psychological and related knowledge is essential to the fullest attainment of health.

Governments have a responsibility for the health of their peoples which can be fulfilled only by the provision of adequate health and social measures.

Article 1

The objective of the World Health Organization (hereinafter called the Organization) shall be the attainment by all peoples of the highest possible level of health.

While the definition of health by WHO is often criticized for its spacious character, its task is to set a standard to ensure a process of constant health improvement. This improvement should be achieved by elaborating regulations and taking actions that support scientific research, the implementation of medical innovations, and their global dissemination.

WHO factsheet 323 explains how exactly human rights apply to healthcare and what exactly member states’ duties are in order to help everyone have the highest attainable level of health.

The right to health includes both freedoms and entitlements.

Freedoms include the right to control one’s health and body (e.g. sexual and reproductive rights) and to be free from interference (e.g. free from torture and from non-consensual medical treatment and experimentation).

Entitlements include the right to a healthcare system that gives everyone an equal opportunity to enjoy the highest attainable level of health.

A human rights-based approach to health provides strategies and solutions to address and rectify inequalities, discriminatory practices, and unjust power relations, which are often at the heart of inequitable health outcomes.

The goal of a human rights-based approach is that health policies, strategies, and programs are all designed with the objective of progressively improving everyone’s enjoyment to the right to health. Interventions to reach this objective adhere to rigorous principles and standards, including:

Non-discrimination: The principle of non-discrimination seeks “…to guarantee that human rights are exercised without discrimination of any kind based on race, colour, sex, language, religion, political or other opinion, national or social origin, property, birth or other status such as disability, age, marital and family status, sexual orientation and gender identity, health status, place of residence, economic and social situation”.

Availability: There must be a sufficient quantity of functioning public health and healthcare facilities, goods and services, and programs.

Accessibility: Health facilities, goods and services must be accessible to everyone. Accessibility has 4 overlapping dimensions:

non-discrimination;

physical accessibility;

economical accessibility (affordability);

information accessibility.

Acceptability: All health facilities, goods, and services must be respectful of medical ethics and culturally appropriate as well as sensitive to gender and life cycle requirements.

Quality: Health facilities, goods, and services must be scientifically and medically appropriate and of good quality.

Accountability: States and other duty-bearers are answerable for the observance of human rights.

Universality: Human rights are universal and inalienable. All people everywhere in the world are entitled to them.

It is important to note that the right to health does not mean that countries are obligated to ensure the highest attainable level of health if ensuring the availability of every existing medical technology to everyone is beyond their capabilities. It means that countries should aspire to provide the best medical services possible with their existing capabilities.

Hence, to reach the goal of bringing the various aging processes under medical control and free everyone from the burden of age-related diseases, the longevity community has to be an active stakeholder.

Here is a list of the most important activities to foster progress:

To take part in the development of appropriate regulations supporting new technologies’ development and implementation as well as to disseminate corresponding knowledge and lifestyle practices;
To facilitate scientific research on aging and rejuvenation, including direct fundraising for research institutions and projects;
To maintain public dialogue about aging, its implications for social and economic development, and the potential of rejuvenation biotechnologies to address the challenges related to aging populations.

Date Posted: December 9, 2016

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CellAge

Our society has never aged more rapidly; one of the most visible symptoms of our changing demographics is an exponential increase in the incidence of age-related diseases, including cancer, cardiovascular diseases and osteoarthritis.

Not only does aging have a negative effect on the quality of life among the elderly, it causes a significant financial strain on both private and public sectors. As the proportion of older people increases, so does health care spending.

According to a WHO analysis, the annual number of new cancer cases is projected to rise to 17 million by 2020 and reach 27 million by 2030. Similar trends are clearly visible in other age-related diseases, such as cardiovascular disease. Few effective treatments that address these challenges are currently available, and most of them focus on a single disease rather than adopting a more holistic approach to aging.

Recently, a new approach that has the potential to significantly alleviate these problems has been validated by a number of in vivo and in vitro studies. It has been demonstrated that senescent cells (cells that have ceased to replicate due to stress or replicative capacity exhaustion) are linked to many age-related diseases. Furthermore, removing senescent cells from mice has been recently shown to drastically increase mouse healthspan (the period of life free from serious diseases).

Here at CellAge, we are working hard to help translate these findings into humans!

CellAge, together with a leading synthetic biology partner, Synpromics, is poised to develop a technology allowing for the identification and removal of harmful senescent cells. Our breakthrough technology will benefit both the scientific community and the general public.

In short, CellAge is going to develop synthetic promoters that are specific to senescent cells, as promoters that are currently being used to track senescent cells are simply not good enough to be used in therapies. The most prominently used p16 gene promoter has a number of limitations, for example.

First, it is involved in cell cycle regulation, which poses a danger in targeting cells that are not dividing but not senescent either, such as quiescent stem cells.

Second, organism-wide administration of gene therapy might, at present, be too dangerous. This means that only senescent cells in specific organs might need to be targeted, and the p16 promoter does not provide this level of specificity.

Third, the p16 promoter is not active in all senescent cells. Thus, after therapies utilizing this promoter, a proportion of senescent cells would still remain. Moreover, the p16 promoter is relatively large (2.1kb), making it difficult to incorporate into current gene therapy vehicles.

Finally, the p16 promoter might not be strong enough to achieve the intended therapeutic effect.

CellAge will be constructing a synthetic promoter that has the potential to overcome all of these limitations. A number of gene therapy companies, including uniQure, AGTC, and Avalanche Biotech, have successfully targeted other types of cells using this technology. With your help, we will be able to use the same technology to develop tools and therapies for accurate senescent cell targeting.

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