Boosting Mitochondrial Quality Control to Combat Alzheimers

Date Posted: December 8, 2017

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Scientists at the École polytechnique fédérale de Lausanne (EPFL) have found a way to make mitochondria more resistant to damage, which could potentially be used to halt Alzheimer’s and other, similar, diseases.

Globally, Alzheimer’s disease is the most common form of dementia and cause of neurodegeneration. It causes brain damage and symptoms such as long-term memory loss. It is an amyloid-based disease, with the characteristic hallmark being the formation of toxic plaques in the brain made from the aggregated beta-amyloid inside the neurons.

Improving mitochondrial quality control

Diseases like Alzheimer’s are the result of the loss of proteostasis, which leads to the creation of sticky misfolded proteins, which form plaques by bonding together. There is still no cure for the disease, and it causes tremendous suffering while posing a considerable burden on the public health system. Many treatments have focused on trying to reduce the formation of the plaques, but, as of yet, the results are inconclusive. One group of researchers has tried a different approach and is looking at Alzheimer’s as a metabolic disease.

The new study focused on the mitochondria, the powerhouses of the cell that produce the energy needed for cellular functions central to metabolism[1]. The research team showed that in worms and mice, they could make the mitochondria more robust and resistant to a particular form of protein stress, allowing them to better protect themselves and, more importantly, reduce the accumulation of amyloid plaques.

During the aging process, cells are exposed to increased levels of damage, and that includes damage to their mitochondria. Damaged mitochondria become dysfunctional, and cells normally replace them via a process known as mitophagy, a selective degradation of the mitochondria by autophagy.

Unfortunately, over time, our cells become increasingly poor at removing these problem mitochondria, thus leaving them vulnerable to Alzheimer’s disease.

The researchers identified two key processes that act as a quality control system for the mitochondria. First, there is the process of mitophagy, which recycles damaged mitochondria, and second, there is the mitochondrial unfolded protein response (UPRmt), which shields mitochondria from stress. Taken together, these processes are one possible solution to reducing mitochondrial damage and could help combat diseases like Alzheimer’s.

Better recycling improves cognition

It has been known for some time that the mitochondria are dysfunctional in the brains of Alzheimer’s patients, but this is the first evidence suggesting that the disease might be combated by boosting these quality control systems. These two processes are present in C.elegans flatworms, mice, and humans, so worm and mouse research could translate well into human beings. The researchers decided to try activating these systems using a drug to see if they could boost protection and quality control in the mitochondria.

They used the antibiotic doxycycline and the vitamin nicotinamide riboside (NR), both known to activate the UPRmt and mitophagy systems in worm models of Alzheimer’s. They noticed that the health and lifespan of treated worms increased dramatically compared with untreated controls, and the formation of plaques was also significantly reduced. Intriguingly, they also observed similar improvements when they activated the same two systems in human neuronal cells in culture using the same two drugs.

Finally, the researchers tested NR in a mouse model of Alzheimer’s disease. They observed the same improvement to mitochondrial function and reduction of plaques as seen in the flatworms. Perhaps most importantly, the researchers noted a dramatic improvement in the cognitive function of the mice.

Conclusion

The usual caveats apply; the results are only so far confirmed in flatworms, Alzheimer’s model mice and human cells in culture. However, the two target quality control systems are present in all three species and can be activated in the same way, which leaves some room for optimism. Will it prove to be more effective than the direct removal of amyloids? Or could it even be a co-therapy for those other approaches? Only time and a clinical trial will tell.

Literature

[1] Vincenzo Sorrentino, Mario Romani, Laurent Mouchiroud, John S. Beck, Hongbo Zhang, Davide D’ Amico, Norman Moullan, Francesca Potenza, Adrien W. Schmid, Solène Rietsch, Scott E. Counts, Johan Auwerx.Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity. Nature 06 December 2017. DOI: 10.1038/nature25143.

Date Posted: December 5, 2017

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SENS: Progress in the Fight Against Age-Related Diseases

Given that there is to be a Reddit AMA on December 7th with Dr. Aubrey de Grey in the Futurology subreddit, we think it’s a great time to have a look at the progress that the SENS Research Foundation has made in tackling the aging processes. What follows is a brief summary of some of the highlights of their research efforts as well as the details of the AMA, in which you can ask Aubrey anything you like about his work.

Today, there are many drugs and therapies that we take for granted. However, we should not forget that what is common and easily accessible today didn’t just magically appear out of thin air; rather, at some point, it used to be an unclear subject of study on which “more research was needed”, and even earlier, it was just a conjecture in some researcher’s head.

Hopefully, one day not too far into the future, rejuvenation biotechnologies will be as normal and widespread as aspirin is today, but right now, we’re in the R&D phase, so we should be patient and remind ourselves that the fact that we can’t rejuvenate people today doesn’t mean that nothing is being done or has been achieved to that end. On the contrary, we are witnessing exciting progress in basic research—the fundamental building blocks without which rejuvenation, or any new technology at all, would stay a conjecture.

In particular, SENS Research Foundation (SRF), a pioneering organization of the field, is sometimes unjustly accused by skeptics for failing to produce results. But produce results it has, and many at that. Skeptics either decide to ignore them or do not have access to reliable sources. For the benefit of the latter, we’ll discuss below what has been achieved by SRF over the past few years, in relation to the infamous “seven deadly things”, the seven categories of damage that aging causes as described in the SENS repair approach.

Mitochondrial mutations

In a nutshell, a mitochondrion is a cell component that is in charge of converting food nutrients into ATP (adenosine triphosphate), a chemical that powers cellular function. Your DNA is contained within the nucleus of each of your cells, but this isn’t the only DNA in your body; mitochondria have their own DNA (known as mtDNA), likely because, at the dawn of life, they were independent organisms that eventually entered a symbiotic relationship with eukaryotic cells, such as those found in our bodies.

Unfortunately, as mitochondria produce ATP, they also produce so-called free radicals as a byproduct—atoms with unpaired electrons that seek to “pair up” with other electrons, and to do so, they’ll gladly snatch them from other molecules nearby, damaging them. As free radicals are created by mitochondria, they’re very close to mtDNA, which is thus very susceptible to being damaged and undergoing mutations.

Mitochondria with damaged DNA may become unable to produce ATP or even produce large amounts of waste that cells cannot get rid of. To add insult to injury, mutant mitochondria have a tendency to outlive normal ones and take over the cells in which they reside, turning them into waste production facilities that increase oxidative stress—one of the driving factors of aging.

MitoSENS: How to solve this problem, and how far we’ve got

Cell nuclei are far less exposed to free-radical bombardment than mitochondria, which makes nuclear DNA less susceptible to mutations. For this reason, the cell nucleus would be a much better place for mitochondrial genes, and in fact, evolution has driven around 1000 of them there. Through a technique called allotopic expression, we could migrate the remaining genes to the nucleus and solve the problem of mitochondrial mutations.

Human-made allotopic expression was a mere theory until late 2016, when, thanks to the successful MitoSENS crowdfunding campaign on Lifespan.io, a proof of concept was finally completed. Dr. Matthew O’Connor and his team managed to achieve stable allotopic expression of two mitochondrial genes in cell culture, as reported in the open-access paper[1] they published in the journal Nucleic Acids Research. As Aubrey de Grey himself explains in this video, of the 13 genes SRF is focusing on, it’s now managed to migrate almost four. This had never been done before and is a huge step towards addressing this aspect of aging in humans. In the past few months, the MitoSENS team has presented its results around the world and worked on some problems encountered in the project.

A list of SRF-funded papers on the topic of mitochondrial mutations can be found here. A more detailed description of its intramural MitoSENS research can be found here.

Lysosomal dysfunction

Lysosomes are digestive organelles within cells that dispose of intracellular garbage—harmful byproducts that would otherwise harm cells. Enzymes within lysosomes can dispose of most of the waste that normally accumulates within cells, but some types of waste, collectively known as lipofuscin, turn out to be impossible to break down. As a result, this waste accumulates within the lysosomes, eventually making it harder for them to degrade even other types of waste; in a worst-case scenario, overloaded lysosomes can burst open and spread their toxic contents around.

This eventuality is especially problematic for cells that replicate little or not at all, such as heart and nerve cells—they’ve got all the time in the world to become swamped in waste, which eventually leads to age-related pathologies, such as heart disease and age-related macular degeneration.

LysoSENS: How to solve this problem, and how far we’ve got

As normal lysosomal enzymes cannot break down lipofuscin, a possible therapy could equip lysosomes with better enzymes that can do the job. The approach suggested by SRF originates with ERT—enzyme replacement therapy—for lysosomal storage diseases. This involves identifying enzymes capable of breaking down different types of intracellular junk, identifying genes that encode for these enzymes, and finally delivering the enzymes in different ways, depending on the tissues and cell types involved.

SRF funded a preliminary research project on lipofuscin clearance therapeutics at Rice University[2] and another project relating to atherosclerosis and the clearance of 7-ketocholesterol[3] (a lipofuscin subtype), which eventually spun into Human Rejuvenation Biotechnologies, an early-stage private startup funded by Jason Hope.

A LysoSENS-based approach is currently being pursued by Dr. Kelsey Moody, who used to work at SRF. Dr. Moody has been working on an ERT treatment for age-related macular degeneration. The treatment consists in providing cells of the macula (a region of the eye’s retina) with an enzyme capable of breaking down a type of intracellular waste known as A2E. The treatment, called LYSOCLEAR, is being worked on by Moody’s company Ichor Therapeutics, which earlier this year has announced a series A offering to start Phase I clinical trials of its product.

If LYSOCLEAR proves successful, it could pave the way for future LysoSENS-based therapies to treat lysosomal dysfunction in different tissues.

A list of SRF-funded papers on the topic can be found here.

Cellular senescence

As cells divide, their telomeres—the end-parts of chromosomes protecting them from damage—shorten. Once a critical length has been reached, cells stop dividing altogether and enter a state known as senescence. Senescent cells are known to secrete a cocktail of chemicals called SASP (Senescence Associated Secretory Phenotype), which promotes inflammation and is associated with several age-related conditions.

However, senescent cells are a bit of a double-edged sword; as explained by Professor Judy Campisi during RB2016, as long as they’re not too numerous, senescent cells carry out an anti-cancer function and may promote wound healing; however, too many of them have the opposite effect, and on top of that, they induce neighboring cells to undergo senescence themselves, starting a dangerous spiral.

Normally, senescent cells destroy themselves via programmed cell death, known as apoptosis, and are then disposed of by the immune system, but some of them manage to escape destruction, and as the immune system declines with age, this gets worse.

The result is that late in life, senescent cells have accumulated to unhealthy amounts and significantly contribute to the development of age-related diseases. Osteoarthritis, cardiovascular diseases, cancer, metabolic disorders such as diabetes, and obesity are all linked to the chronic age-related inflammation to which senescent cells contribute.

ApoptoSENS: How to solve this problem, and how far we’ve got

The proposed SENS solution is straightforward: if senescent cells become too numerous, then they need to be purged. Since they are useful in small amounts, the optimal solution would be periodically removing excess senescent cells without eradicating them entirely—and more importantly, leaving other cells unharmed.

This could potentially be achieved by either senolytic drugs or gene therapies that selectively target senescent cells and trigger programmed cell death. Indeed, a great deal of recent focus by researchers have been on finding ways to remove senescent cells using senolytic therapies.

Another approach that could complement senolytics is to address why the immune system stops clearing senescent cells effectively in the first place. This approach focuses on macrophages and other immune cells involved in clearing senescent cells, aiming to reduce inflammation so that these cells begin to function properly again. The irony is that as inflammation rises with age, the immune system that is supposed to clear senescent cells and keep inflammation levels down actually starts to create more inflammation and becomes part of the problem by not doing its job properly.

SRF has funded a number of studies on the subject of cellular senescence, and it’s recently begun working on a project in collaboration with the Buck Institute for Research on Aging, which is focusing on the immune system and its role in clearing senescent cells. Another extramural project, again with the Buck Institute, is focussed on SASP inhibition.

Senescent cell clearance has been all the rage for the past two years or so; Lifespan.io has hosted the MMTP project, which focused on testing senolytics in mice, and this was later followed by CellAge’s project to design synthetic biology-based senolytics.

There are other companies that have joined the race to add senescent cell clearance to the standard toolkit of doctors, such as Unity Biotechnology and Oisin Biotechnologies.

Unity’s approach uses a drug-based approach to senolytics and is scheduled to enter human clinical trials in 2018. A number of other research teams are also developing drug-based approaches to removing senescent cells, and the competition looks set to be fierce in this area in the coming years.

Oisin’s approach, which we discussed here, makes use of suicide genes and hopefully will be tested in clinical trials not too far into the future, thanks to venture funding presently being collected. If this system can be made to work, it will allow very selective targeting of senescent cells by destroying only those giving off a target gene or genes. Thus, if a unique gene expression profile for senescent cells is determined, it would mean only those cells were destroyed, with less risk of off-target effects.

Oisin owes its existence to the SENS Research Foundation and the Methuselah Foundation, which provided the necessary seed funding. Kizoo Technology Ventures has also invested in Oisin.

Extracellular crosslinks

The so-called extracellular matrix is a collection of proteins that act as scaffolding for the cells in our body. This scaffolding is rarely if ever replaced, and a really bad consequence of this is that its parts eventually end up being improperly linked to each other through a process called glycation—the reaction of (mainly) blood sugar with the proteins that make up the extracellular matrix itself.

The resulting cross-links impair the function and movement of the linked proteins, ultimately stiffening the extracellular matrix, which makes organs and blood vessels more rigid. Eventually, this leads to hypertension, high blood pressure, loss of skin elasticity, and organ damage, among other problems.

While there are different types of cross-links—known as AGEs, short for advanced glycation end-products—glucosepane is arguably the worst, being the most common and long-lasting of all, and the body is very ill-equipped to break it down.

GlycoSENS: How to solve this problem, and how far we’ve got

In order to eliminate unwanted cross-links, the SENS approach proposes to develop AGE-breaking molecules that may indeed sever the linkages and return tissues to their original flexibility. Of course, in order to do so, crosslink molecules need to be available for research to attempt to combat them with drugs, and especially in the case of glucosepane, this has been a problem for years.

Glucosepane is a very complex molecule, and very little of it can be extracted from human bodies, and not even in its pure form. This has been greatly hampering the progress of research against glucosepane, but thankfully, this problem is now solved thanks to a collaboration between the Spiegel Lab at Yale University and the SENS Research Foundation, which financially supported the study. It is now possible to fully synthesize glucosepane, allowing for researchers to create it on demand and at a cost-effective price.

The Spiegel Lab’s scientists are now developing anti-glucosepane monoclonal antibodies to cleave unwanted cross-links. The collaboration between the Spiegel Lab and SRF dates all the way back to 2011, but it was in 2015 that the Lab announced its success and published a related paper [4] in the journal Science.

Further information on glucosepane cross-link breakers can be found in this interview with Dr. David Spiegel from Yale University on Fight Aging!; a list of studies on the subject funded or otherwise supported by the SRF is available here.

SRF also worked with the Babraham Institute on a cross-link quantification project.

Let’s help SRF move forward

As we have seen, SRF has produced plenty of results; the projects we discussed are either recent or ongoing, and yet others were carried out in the past. However, much more work still needs to be done before the first rejuvenation therapies move from the lab to the clinic.

If you would like to know more about SRF’s work or have questions not covered in this article, you have a great opportunity to ask none other than Dr. Aubrey de Grey himself during his AMA (“ask me anything”) on Reddit. On December 7, at 14:00 PST (22:00 UTC, 17:00 EST), Aubrey will be on /r/futurology to answer any question at all, so save the date! The Futurology mods are also taking pre-AMA questions here if you cannot wait to ask Aubrey anything or cannot make the event.

Readers who wish to donate to SRF to help the organization in its crusade against the ill health of old age can do so by contributing to its winter fundraiser or even becoming SRF patrons. Have a look at SRF’s donation page to find out more.

Literature

[1] Boominathan, A., Vanhoozer, S., Basisty, N., Powers, K., Crampton, A. L., Wang, X., … & O’Connor, M. S. (2016). Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA Complex V null mutant. Nucleic acids research, 44(19), 9342-9357.

[2] Gaspar, J., Mathieu, J., & Alvarez, P. (2016). A rapid platform to generate lipofuscin and screen therapeutic drugs for efficacy in lipofuscin removal. Materials, Methods and Technologies, 10, 1-9.

[3] Mathieu, J. M., Wang, F., Segatori, L., & Alvarez, P. J. (2012). Increased resistance to oxysterol cytotoxicity in fibroblasts transfected with a lysosomally targeted Chromobacterium oxidase. Biotechnology and bioengineering, 109(9), 2409-2415.

[4] Draghici, C., Wang, T., & Spiegel, D. A. (2015). Concise total synthesis of glucosepane. Science, 350(6258), 294-298.

Date Posted: December 4, 2017

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Dr. Aubrey de Grey: Undoing Aging

Dr. Aubrey de Grey is the Chief Science Officer and founder of the SENS Research Foundation (SRF) and one of the original proponents of a damage repair-based approach to aging and age-related diseases. His work has inspired many others to think about aging differently and entertain the idea that, perhaps, we do not have to accept the suffering that age-related diseases cause.

In this article, Dr. de Grey writes a summary of the strategy of rejuvenation based on a periodic approach to repairing age-related damage. This approach has steadily gained increasing traction as the data supporting it grows; certainly, the clearance of senescent cells, a SENS approach, has enjoyed great public interest recently. Interestingly, while he certainly is not the only researcher to have suggested the idea, he was talking about removing senescent cells as a therapy back in 2002 [1].

The work of Dr. de Grey has also encouraged others to pursue repair based approaches to aging, including the much-cited Hallmarks of Aging, which is almost certainly inspired by SENS [2].

The SRF has actively funded research into senescent cells, and companies like Oisin are a direct result of the work of the foundation and are now developing therapies to bring to market. Imagine what might be achieved if all seven of the SENS damages received the same level of support and interest. As a community, we can help to make this happen and maybe have a shot at healthy and longer lives as a result.

Conclusion

In the face of the increasing amount of research and data in support of SENS, there has been a large shift in academic enthusiasm and support for the repair approach to aging. The stakes are high here, but ultimately, if we can develop the tools and methods we need to address the damage that aging causes, we have a real shot at longer and most importantly healthier lives.

Literature

[1] Grey, A. D., Ames, B. N., Andersen, J. K., Bartke, A., Campisi, J., Heward, C. B., … & Stock, G. (2002). Time to talk SENS: critiquing the immutability of human aging. Annals of the New York Academy of Sciences, 959(1), 452-462.

[2] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

Date Posted: December 1, 2017

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Rejuvenation Roundup November 2017

November has been a busy month in the world of rejuvenation biotechnology and life extension, as there has been both really good news and some rather bad news. Let’s have a look together, starting with the bad news and then moving on to decidedly more uplifting things.

Healthy aging and the WHO agenda

It appears that WHO has forgotten to include priorities related to aging in its 13th draft programme of work 2019-2023. This extremely important issue was popularised thanks to the efforts of Dr. Ilia Stambler, who recently co-authored a paper on the importance of healthy longevity as a topic for the WHO programme. The authors of this jointly developed position include leaders of the International Society on Aging and Disease (ISOAD), American Federation for Aging Research (AFAR), International Federation on Ageing (IFA), International Association of Gerontology and Geriatrics – IAGG (European Region and Asia-Oceania), International Longevity Center – Australia, the Gerontological Society of the Russian Academy of Sciences, and the African Society for Ageing Research and Development (ASARD). LEAF board director Elena Milova raised the same issue here, and LEAF’s official position has also been discussed by the Russian newspaper Medvestnik.

Multiple pro-longevity organizations have invited community members to take part in the open consultation on the programme in order to promote the inclusion of the issues of the aging population. Thanks to a joint effort, WHO has received plenty of feedback (90% out of 400 responses) lamenting the absence of aging in the draft, and now WHO will hopefully consider including its earlier Global Strategy and Action Plan on Aging and Health in the draft. Advocacy efforts are in progress.

SENS Winter Fundraiser

Like every year, the folks at the SENS Research Foundation have launched their end-of-year winter fundraiser, and the goal this year is $250,000. The generous support of donors and patrons is essential in the fight against aging, and while helping the cause is rewarding in and of itself, a little incentive is never unwelcome; this year, SENS is doing something a bit different.

Anyone who contributes $250 or more between October 15th and December 31st will automatically receive a SENS Research Foundation t-shirt just like the ones worn by the team. Anyone who donates $500 or more will get a cool SENS Research Foundation Polo shirt. You can find out more about the winter fundraiser here.

LEAF Conference in Moscow on November 4

LEAF, in collaboration with Singularity University Moscow Chapter and consulting group Deloitte, hosted the conference “6 ways to talk to people about aging” in Moscow. Six brilliant speakers shared their insights with the audience on how best to inform society about the potential and the advancement of gerontology and preventive medicine.

The list of speakers included Jose Luis Cordeiro, fellow of the World Academy of Art and Science (WAAS), director of life extension advocacy organization Humanity Plus; Valerija Udalova (Pride), director of Russian cryocompany KrioRus and methodologist of the Human Aging System Diagram project; Eugeny Kuznetsov, ambassador of Singularity University in Russia; Maxim Kholin, co-founder of the group «Gero», which develops therapies and blockchain solutions for significant lifespan extension; Anastasia Egorova, vice president of the Foundation Science for Life Extension and director of Open Longevity ICO; and Carlos Garcia Hernandez, director of Lolabooks publishing house, which released the book by Aubrey de Grey and Michael Rae, Ending Aging, in Spanish, and translated books by Ray Kurzweil and other great thinkers of our time.

The conference was attended by nearly 200 people! Video recordings of the event will soon be available on our website as well as Facebook and Youtube pages.

Lifespan.io on Kurzgesagt… again!

Kurzgesagt has released the second video on aging created with the help of the Lifespan.io team on November 3. While the first video introduced viewers to the possibility of ending aging within a few decades, discussing why we should do this, this new video discusses some of the medical technologies currently being developed to address the various hallmarks of aging. If you’ve not done so yet, we definitely recommend you watch these videos! It has been a pleasure to work with Kurzgesagt, and we look forward to future collaborations.

Support for rejuvenation biotechnology and LEAF is growing

A most welcome outcome of our collaboration with Kurzgesagt has been a large increase in our followers and supporters. Judging by the positive responses from the majority of the audience to these videos, it seems very clear that the dissenters are very much in the vocal minority.

Fight Aging! Matching Fund and other news

Just as traditional as the SENS Winter Fundraiser, the matching fund put up by Fight Aging! is running since October 15th and will continue until December 31st. Reason, Josh Triplett, and Christophe and Dominique Cornuejols have put together a $36,000 fund with which they’ll match the first full year of donations made to SENS by anyone who signs up as a monthly patron before the end of 2017.

In other news from FA!, Reason reported an open-access paper discussing the connection between mitochondrial dysfunction and cellular senescence in relation to age-related respiratory diseases, such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. The degradation of defective mitochondria declines in senescent cells and the paper suggests that this might contribute to the pro-inflammatory aspects of cellular senescence.

Interview with Dr. Michael Fossel

Our friends at Geroscience have published the second part of their interview with Dr. Michael Fossel, a leading expert on telomere attrition and telomerase therapy.

The first part of the interview, published in October, discusses his views on aging and the reasons why he focuses on telomeres especially; in the second part, Dr. Fossel explains how telomere replenishment could be done and the benefits we can expect to reap. Check it out!

A panel about life extension prospects in the near future

Biogerontology Research Foundation Trustee Dmitry Kaminskiy and Chief Science Officer Dr. Alex Zhavoronkov spoke at the Aging and Longevity Panel at the Financial Times Global Pharmaceutical and Biotechnology Conference in London on November 10th, 2017, alongside Dr. Aubrey de Grey, Chief Science Officer of SENS Research Foundation, and Joseph Antoun, Chairman of the Global Healthspan Policy Institute.

The discussion panel focused on the prospects for geroscience to deliver practical solutions to aging in the near future. This is of particular interest given that the topic of targeting aging to prevent disease has been openly discussed at one of the largest European biotechnology conferences, at which all the major pharmaceutical companies were present. Interest in the field and preventative medicine has grown dramatically in the last few years, and this is yet more indication of its rising popularity.

Conversations with the future

Nikola Danaylov’s new book “Conversations with the future” is trending on Amazon. There is an interview with Michael Fossel, PhD, MD, professor of Clinical Medicine of Michigan State University, a famous researcher of aging. The section discusses the main mechanisms of aging, the possibility to manipulate them and related emerging technologies while touching upon some of the most frequent ethical issues related to getting rid of aging. Readers can also find a few recommendations of currently available methods to extend healthy life.

Coming up in December

SENS AMA

On December 7th, in conjunction with the ongoing winter fundraiser, Dr. Aubrey de Grey, Chief Science Officer of SENS Research Foundation, will be on Reddit for an AMA (“ask me anything”). Dr. Aubrey de Grey is one of the original proponents of a repair based approach to aging and age-related diseases and this is your opportunity to ask him about the progress being made in research, his thoughts about the future or whatever else you might like to know about this fascinating scientist.

Anyone with a question for Dr. de Grey will have a chance to ask him personally in the /r/futurology subreddit, starting at 2 PM PST (5 PM EST, 10 PM UTC). If you want to know how SENS research is progressing, or ask Aubrey anything at all, this is your chance!

More LEAF events

LEAF is hosting two events in Moscow in December. On December 6, LEAF Director Elena Milova is giving a lecture called “How to defeat aging?” at one of the state libraries. The week after, Pam Keefe, member of the advisory board of the Coalition for Radical Life Extension and co-organizer of the RAADFEST Bangkok conference, is visiting Moscow, and we will use this opportunity to organize a friendly discussion of longevity communication strategies entitled “Revolution against aging: principles, methods, examples”.

Project for Awesome

LEAF is taking part in the “Project for Awesome 2017” contest taking place on December 15-17, and we hope that you will come to support us by voting for our videos and making your own videos to say why you support the work we do. Please reference the Lifespan Extension Advocacy Foundation in the video description.

Date Posted: November 14, 2017

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Why do Some People Fear Using Science to Live Longer Healthy Lives?

With the recent increase of enthusiastic support for the idea of defeating aging, I really shouldn’t be complaining about the lingering holdouts opposing the idea of living healthy and longer lives for whatever reason. Nonetheless, I feel compelled to point out the jarring contradiction of a species whose members are constantly on the lookout to avoid danger, yet need to be reassured that at some point they will die and that science is by no means trying to prevent that.

Fear of life extension

This curious phenomenon was pointed out earlier this year by James Goodwin in the journal of the Gerontological Society of America[1]. In his article “Fear of life extension”, he argues that the commandment of geriatrics is “quality, not quantity” because policymakers fear a future in which longer life means overpopulation of nursing homes, and as a consequence, researchers working on interventions on aging need to clearly state that their goal is just making our final years a little better—but making us live longer? God forbid, no! We only want to live in perfect health for about 80 or 90 years, then magically drop dead for no apparent reason.

Quite concisely, Goodwin explains that you can’t have significant longevity without an equally significant improvement of your health, and vice-versa; so did I, in my own small way, in this article. Yet, the idea of living longer than the status quo, or even suggesting that this might be a good thing, is almost blasphemous to some, and I’m not talking just about academics bending the truth a little for the sake of getting their next grant. “Quality, not quantity” has become a mantra, not only because of the largely unjustified concerns about the potential downsides of longer lives but also because it has somehow been incorporated into the set of conventional wisdom that nearly no one dares challenging for the simple reason that nearly no one else does.

Don’t worry—you’ll die anyway

I’ve personally talked to a number of people who think it would make no sense if your life never came to an end; there has to be closure for it to have meaning, they say. I’ve spoken to people who “know” they’ll want to die at some point, and I’m not talking about bitter old men who’re tired of their failing bodies and the many disappointments life has served them; I’m talking about barely adult people in their early twenties, with their health and looks still perfectly in place and pretty much a whole “normal-length” life to live. This, I must ascribe to the power that clichés have on the human mind; a lot of people repeat that accepting, wanting, and cherishing the finitude of life is wise, so it must be true, and so they follow suit. That sort of thing.

And it is no joke because advocates of rejuvenation often need to reassure people that this is not about eliminating death; it’s not about making you unable to die. Granted, that is true—rejuvenation doesn’t make you immortal—but I’ve lost count of articles and videos on the subject of aging that, while discussing advancements that may improve our lives and maybe even make them a little longer, still make it absolutely clear to their audience that they needn’t worry—fear not, you’ll still die at some point! Whew, what a relief! For a second there, I actually thought I’d be able to get out of life alive.

If you think it through, though, this is most strange. Like most if not all creatures on this planet, we have evolved to avoid danger and situations that might cause our own demise. To put it bluntly, we have evolved to fear death, yet we have people who say there’s nothing to fear in it.

If that’s so, why do we have hospitals to fix us up, ambulances rushing to accident sites in the hopes of making it in time to save the most people, safety measures to minimise our risk of death? Why do we look after our young, why do we take medicines and vaccines, why do we have suicide helplines? If there’s nothing to fear in death, why do we go through so much trouble to avoid it? Seems a bit odd to me.

Just to be clear—I don’t fear what lies after death because my personal view is that there’s nothing at all on the other side; and while I do fear a painful death, that’s not what I’m getting at here. Death would put an end to all I like and love, and quite frankly, that would kind of throw a spanner in my works. If something had gone wrong with me and I didn’t have the instinct to fear death anymore, I’d probably have a harder time avoiding death, but I’d still have plenty of non-fear-related reasons to want to avoid it.

Conclusion

What are the roots of this fear of longevity? Why is it that it almost can’t be spoken about? Is it the misplaced concern of longer decrepitude? Is it a fox-and-grapes situation? Is it some sort of Stockholm syndrome that makes us grow fond of our persecutor? Is it the fear of overpopulation and boredom? Maybe a combination of all of these possibilities?

I’m not sure, but I do know that it might be a roadblock on the way to a world without age-related diseases. As I said at the beginning, there certainly are reasons to think that the roadblock, if it is even there, is slowly being dismantled; nonetheless, I suggest not to underestimate this danger and to keep doing our best to explain why healthy longevity, not the finitude of life, needs to be cherished.

Literature

[1] Goodwin, J. S. (2017). Fear of life extension.

Date Posted: November 8, 2017

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Does WHO 5 Year Plan Leave Healthy Aging Out of the Picture?

When it comes to healthcare, WHO remains the global flagship in terms of setting priorities and adjusting policies in the ever-changing landscape of healthcare needs. In the past few years, WHO has been making steps towards preparing our society to handle the “silver tsunami” and the increasing needs of the elderly population, which is expected to reach 22% of the global population by 2050.

The last 12th General Programme of Work, adopted by the World Health Assembly in May 2013, listed population aging and morbidity of age-related diseases as one of the points of great concern. However, in the recent Draft thirteenth general programme of work 2019–2023, the priorities related to aging and age-related disease are… gone.

What is this, a tragic accident or the worst example of ageism at the level of the global policymaking? Can the Open Consultation running until November 15 help bring healthy aging back into the WHO agenda? You will also find The LEAF Position regarding the Draft programme at the end of this article, but first, let’s discuss why this is important to keep healthy aging among the top priorities.

After all the efforts to introduce aging and the problems of the growing share of the elderly into the international agenda, WHO seems to fall back by 30 years and leave this most important question out the discourse for the next 5 years. While the Draft thirteenth general programme of work 2019–2023 claims to be based on the Sustainable Development Goals, it is clear that it is throwing out the problems of the elderly. For instance, the SDG indicated the need to promote the development and implementation of medicines against noncommunicable diseases; this never made it to the new draft, and neither did the four main diseases with the highest mortality rates. Here are the quotes from the SDG indicators:

3.4

By 2030, reduce by one-third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being

3.4.1

Mortality rate attributed to cardiovascular disease, cancer, diabetes or chronic respiratory disease …

3.B Support the research and development of vaccines and medicines for the communicable and non-communicable diseases that primarily affect developing countries, provide access to affordable essential medicines and vaccines, in accordance with the Doha Declaration on the TRIPS Agreement and Public Health, which affirms the right of developing countries to use to the full the provisions in the Agreement on Trade-Related Aspects of Intellectual Property Rights regarding flexibilities to protect public health, and, in particular, provide access to medicines for all.

The priorities of the new draft moved elsewhere and do not pay much attention to age-related diseases, which account for most deaths among the ones caused by NCDs. Here is how the set of priorities on NCDs is formulated in the draft:

3. Noncommunicable diseases (NCDs), mental health, substance use, road traffic injuries

Reduce tobacco use by 25%
Reduce harmful alcohol use by 10% (per capita consumption)
Keep the levels stable for overweight (including obesity) in children and adolescents
Eliminate industrially produced trans fats
Reduce prevalence of raised blood pressure by 20%
Increase service coverage for severe mental health disorders by 40 percentage points
Reduce road traffic fatalities by 20%

This list is barely touching upon age-related health issues (high blood pressure is probably the most relevant point), while the priorities 1, 2 and 4 are completely different. Looking at this document, we are desperately asking ourselves why WHO is suddenly turning its back on the elderly population and what we shall expect to happen to the previous strategic programs, as the draft mentions that it will also influence the Programme budget of 2018−2019 through a mechanism of resource reallocation. Should we treat it as a warning that the resources previously expected to help fulfill the Global strategy and plan of action on ageing and health are going to be redirected to this new “ageist” set of goals?

WHO is currently running an open public consultation on the draft, and we invite you to take part and provide your view regarding the necessity of keeping the issue of age-related diseases in the WHO agenda in the years to come. However, before we provide you with the position that we are going to send to WHO (the example is at the end of this article), we would like to remind you of the key indicators and documents with which you should be familiar in order to make an informed decision regarding the global healthcare agenda.

The age group 60+ is growing faster than any other

The global population is aging rapidly. Here is a quote from the UN Population Prospects 2017 Revision Key Findings concerning this change:

In 2017, there are an estimated 962 million people aged 60 or over in the world, comprising 13 per cent of the global population. The population aged 60 or above is growing at a rate of about 3 per cent per year. Currently, Europe has the greatest percentage of population aged 60 or over (25 per cent). Rapid ageing will occur in other parts of the world as well, so that by 2050 all regions of the world except Africa will have nearly a quarter or more of their populations at ages 60 and above. The number of older persons in the world is projected to be 1.4 billion in 2030 and 2.1 billion in 2050, and could rise to 3.1 billion in 2100. Over the next few decades, a further increase in the population of older persons is almost inevitable, given the size of the cohorts born in recent decades.

NCDs disproportionately affect people in low- and middle-income countries

Worldwide, infectious diseases have been replaced by chronic non-communicable diseases (NCDs) as the leading causes of death; this is called the epidemiological transition. This transition is associated with the most developed countries, but this is a widespread misconception. According to WHO, NCDs disproportionately affect people in low- and middle-income countries, where more than three-quarters of global NCD deaths – 31 million annually – occur. The most frequent NCDs are cardiovascular diseases (heart attacks and stroke), cancers, chronic respiratory diseases (such as COPD), and diabetes. Here is the quote from the WHO fact sheet regarding NCDs:

Cardiovascular diseases account for most NCD deaths, or 17.7 million people annually, followed by cancers (8.8 million), respiratory diseases (3.9 million), and diabetes (1.6 million).

Chronic diseases make most of the top 10 causes of death globally

If we look at the WHO estimates of the main causes of death globally, we can see that age-related chronic diseases account for the vast majority of deaths, with infectious diseases and road injury comprising a much smaller part:

Most recent WHO strategic documents are focused on age-related issues

This data on population aging, combined with the data on morbidity, informed the previous WHO activities related to aging. In 2015, it released the World report on ageing and health, creating an exhaustive overview of population aging, discussing related health, social and economic changes, and describing the necessary actions to make the older population as healthy as possible. The report set the following definition of healthy aging and its mandatory elements:

Healthy Ageing is the process of developing and maintaining the functional ability that enables well-being in older age.

Functional ability comprises the health-related attributes that enable people to be and to do what they have reason to value. It is made up of the intrinsic capacity of the individual, relevant environmental characteristics and the interactions between the individual and these characteristics.

Intrinsic capacity is the composite of all the physical and mental capacities of an individual.

Environments comprise all the factors in the extrinsic world that form the context of an individual’s life. These include – from the micro-level to the macro-level – home, communities and the broader society. Within these environments are a range of factors, including the built environment, people and their relationships, attitudes, and values, health and social policies, the systems that support them, and the services that they implement.

Well-being is considered in the broadest sense and includes domains such as happiness, satisfaction and fulfilment.

Based on the indicators listed in this report, the Global strategy and plan of action on ageing and health was developed and signed into power in 2016, setting the following strategic objectives and goals to prepare for the Decade of Healthy Aging (2020-2030):

VISION A world in which everyone can live a long and healthy life

STRATEGIC OBJECTIVES 1. Commitment to action on Healthy Ageing in every country 2. Developing age-friendly environments 3. Aligning health systems to the needs of older populations 4. Developing sustainable and equitable systems for providing long-term care (home, communities and institutions) 5. Improving measurement, monitoring and research on Healthy Ageing

PLAN OF ACTION 2016–2020

GOALS 1. Five years of evidence-based action to maximize functional ability that reaches every person. 2. By 2020, establish evidence and partnerships necessary to support a Decade of Healthy Ageing from 2020 to 2030.

This document also points out the need to support the development of innovative interventions to address age-related diseases and their underlying causes:

Finally, better clinical research is urgently needed on the etiology of, and treatments for, the key health conditions of older age, including musculoskeletal and sensory impairments, cardiovascular disease and risk factors such as hypertension and diabetes, mental disorders, dementia and cognitive declines, cancer, and geriatric syndromes such as frailty. This must include much better consideration of the specific physiological differences of older men and women and the high likelihood that they will be experiencing multimorbidities. This could also be extended to include possible interventions to modify the underlying physiological and psychological changes associated with ageing.

The LEAF Position regarding the Draft thirteenth general programme of work 2019–2023

Taking this information into account, we suggest the following position regarding the Draft thirteenth general programme of work 2019–2023 that can provide insight and inspiration for your own position. The Open Consultation will be running until November 15. To take part and share your vision with WHO, please visit this WHO page, scroll down, and fill the mandatory fields of the survey.

The global population is aging rapidly, and according to the UN Population Prospects 2017 Revision, the share of people aged 60+ will make up 22% of the global population by 2050[a]. Sadly, higher life expectancy does not necessarily mean an extension of the healthy period of life, and more people around the globe live longer while suffering from chronic age-related diseases, with the developing countries bearing the most burden.
Most countries already experience epidemiological transition, with non-communicable diseases, particularly age-related diseases, becoming leading causes of death. The most frequent NCDs are cardiovascular diseases (heart attacks and stroke), cancers, chronic respiratory diseases (such as COPD) and diabetes. Cardiovascular diseases account for most NCD deaths, or 17.7 million people annually, followed by cancers (8.8 million), respiratory diseases (3.9 million), and diabetes (1.6 million)[b].
The Sustainable Development Goals set the goal to “reduce mortality rate attributed to cardiovascular disease, cancer, diabetes or chronic respiratory disease” (3.4.1), and to “support the research and development of vaccines and medicines for the communicable and noncommunicable diseases that primarily affect developing countries, provide access to affordable essential medicines and vaccines…” (3.B).
The latest WHO World report on ageing and health (2015) and the Global strategy and plan of action on ageing and health (2016) underline the need to promote healthy aging for all, and they recommend the corresponding set of measures, including better clinical research on the etiology of, and treatments for, the key health conditions of older age, including musculoskeletal and sensory impairments, cardiovascular disease and risk factors such as hypertension and diabetes, mental disorders, dementia and cognitive declines, cancer, and geriatric syndromes such as frailty, along with possible interventions to modify the underlying physiological and psychological changes associated with aging (with consideration of the specific physiological differences of older men and women and the high likelihood that they will be experiencing multimorbidities)[c].
Clinical trials of several innovative interventions that can address the underlying mechanisms of aging, postpone and cure age-related diseases, and extend the healthy period of life (senolytics, thymus regeneration in situ, therapies to regulate NAD+ and improve DNA repair, metformin) are currently being performed, and these interventions can enter the market in the next 5 years. WHO supervision and guidance regarding the implementation of these interventions is required to ensure their rapid, worldwide dissemination, affordability and equal access.
While we recognize the need to promote universal health coverage, to keep fighting infectious diseases and mental illnesses, and to promote the health of women, children and adolescents, we find efforts to ensure healthy aging to be of vital importance for our society’s well-being in the decades to come. If this most important topic will be excluded from the global agenda, and the corresponding funding reallocated to solve other health issues, not only it will be an unhealthy example of ageism at the highest level of policymaking, but our society will also face the growing needs of the increasing older population unprepared and disoriented.
The global and local effects of not addressing these issues can be devastating, posing an increasing burden on healthcare and social protection systems (for instance, public health expenditures in the United States are projected to rise from 6.7 percent of GDP in 2010 to 14.9 percent in the year 2050), causing shortages of professional caregivers for aged patients, which will turn a significant part of the working population into compulsory family caregivers and undermine sustainable economic growth.
In order to extend good health and productivity throughout the life course and to ensure that older people preserve their intrinsic ability for as long as possible, we need to keep working in the directions set by the Global strategy and plan of action on ageing and health (2016), including the promotion of clinical research on possible interventions to modify the underlying physiological and psychological changes associated with aging. Hence, we kindly ask you to include promoting healthy aging as a priority of the Draft thirteenth general programme of work 2019–2023.

[a] United Nations, Department of Economic and Social Affairs, Population Division (2017). World Population Prospects: The 2017 Revision, Key Findings and Advance Tables. Working Paper No. ESA/P/WP/248.

[b] WHO. The top 10 causes of death. Fact sheet. Updated January 2017.

[c] WHO Global Strategy and Action Plan on Ageing and Health,” World Health Organization, accessed November 8, 2017.

Thank you very much for finding time to fill out this survey!

Providing policymakers like WHO with our vision regarding the potential of rejuvenation technologies to tackle the problems related to population aging is very important. This way, we help disseminate information about rejuvenation biotechnologies in our society while we encourage more people to support researchers and to start using the interventions that are already available.

We would like to thank Dr. Ilia Stambler for bringing this matter to our attention.

Date Posted: November 8, 2017

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A Demonstration of Rejuvenation in Old Human Cells

Today, we are going to have a look at a new study that shows that senescent, non-dividing aged cells can be rejuvenated using a new technique.

Before we do that, let’s take a look at what senescent cells are and how cellular senescence protects us from cancer and other harmful diseases.

Cellular senescence protects us from damaged cells

Cellular senescence is a safety mechanism that removes aged and potentially damaged cells from circulation. Having mutated and otherwise damaged cells replicating indefinitely would be a recipe for disaster, so this safety system kicks in to shut down these cells and summon the immune system to dispose of them.

Senescent cells are cells that have ceased replicating in response to damage or environmental stimuli or cells that have reached their replicative limit and have critically shortened telomeres that signal the cells to shut down. Senescent cells do not replicate and generally destroy themselves by programmed cell death, which is known as apoptosis; in some cases, they evade this process and remain in situ, causing inflammation and secreting a range of toxic signals that poison the local tissue.

Over time, the number of senescent cells increases in tissue, leading to a rising background of chronic inflammation that causes the immune system to become increasingly dysfunctional, impairs tissue repair and drives the progression of multiple age-related diseases[1].

The most obvious solution to this problem is to remove these senescent cells periodically from the body, and the removal of senescent cells is exactly what Dr. Aubrey de Grey and the SENS Research Foundation have been proposing for over a decade. This has been the focus of much research in recent years, and a new class of therapies known as senolytics aims to do exactly this.

However, some researchers have been tinkering with ways to reverse senescence in cells instead of the more direct approach of removing the problem in the first place.

Reversing cellular senescence

This senescent state was once thought to be an irreversible process, and while this is certainly true during the normal processes of biology, it is not the case when science intervenes. Using cell reprogramming, cell fate can be changed and senescence can be reversed, as demonstrated once again in a new study that shows another technique to achieve this[2].

Senescence is not a one-way street, and a cell can be reprogrammed back to working order from senescence, provided the correct signals are given to it. In fact, a whole range of cell states can be programmed; it is just a case of working out the correct signals and manipulating the genetic machinery to get the result you want. This is no easy task despite the great progress that has been made in the understanding of cell fate in the last decade.

We now understand how to change some cell states quite well, and we have become adept at resetting some cells back to a pluripotent state. Similar to embryonic stem cells, these cells can then be guided down different paths to create new kinds of cells. More recently, we have discovered that cells do not even need to be reverted back to this pluripotent state; instead, they can be directly changed from one type to another without this additional step via the process of transdifferentiation.

Once cell fate is reprogrammed, senescent cells can be made to begin replicating again, and these cells can even operate at a functionally younger level, with a number of aging markers reversed. The researchers of this study have found another technique to restore senescent cells to work.

They exposed aged cells to analogs of the common supplement resveratrol, which caused splicing factors, which are progressively turned off as we age, to be turned back on. Within a few hours, the cells appeared younger and started to rejuvenate, behaving like younger cells and dividing again.

Conclusion

As interesting as this experiment is, is it really a good idea to bring back senescent cells from their arrested replicative state? Considering that senescent cells are generally senescent for a reason, it seems to be a less than wise approach.

Senescent cells may simply be senescent because they have reached their replicative limit, but they might also be damaged and could be harboring any number of mutations that caused them to shut down in the first place. These mutations could potentially cause them to become cancerous, and indeed, cellular senescence is designed to protect us from this.

So, this approach is a double-edged sword. On one hand, the potential for returning damaged cells to circulation will almost certainly increase the risk of cancer, but on the other hand, the harm that senescent cells cause via their inflammatory secretions is also significant.

It seems that there could be short-term benefits to restoring senescent cells to circulation due to removing their toxic secretions, but in the long term, the risks are not trivial. Senescent cells are generally likely to be damaged, and, really, instead of returning them to work, they should be destroyed as the body intended.

This is why the senolytic approach of destroying these cells offers the most robust and lower-risk option in dealing with senescent cells, and why, in our view, the approach here is inferior and a poor second-best choice in the long-term. If we can simply remove these aged, damaged cells, why would we bother to paper over the problem? The answer seems obvious.

Literature

[1] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

[2] Latorre, E., Birar, V. C., Sheerin, A. N., Jeynes, J. C. C., Hooper, A., Dawe, H. R., … & Harries, L. W. (2017). Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence. BMC cell biology, 18(1), 31.

Date Posted: November 6, 2017

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Why Bringing Aging Under Medical Control Probably Will Not Create a Gerontocracy

As I discussed in another article, rejuvenation biotechnology could potentially allow older adults to continue working and producing wealth for much longer than they can today, thus benefiting society in many ways.

However, some people are concerned that this might do more harm than good; imagine all those rejuvenated old farts holding onto their jobs forever, preventing the young from getting jobs themselves! Not to mention the risk of a gerontocratic world, where powerful older people get a touch too attached to their chairs, never allowing younger people a chance!

New is not always better

If you’re more concerned that dictators could live for centuries, then you should have a look at this article; here, I’m going to deal with another scenario: old, rejuvenated people who hold on to positions of power—not necessarily as heads of countries—or their jobs for a really long time.

Quite frankly, what’s wrong with that?

Just because someone has been in charge of the same position for long, it doesn’t mean that it’s necessarily a bad thing. If you think otherwise, you might be making the assumption I rebutted here, namely that, rejuvenated or not, older people will always tend to do things in old ways, eventually making them a worse choice than younger people. On the contrary, their long experience might make them more fit than others, especially if we’re talking about chronologically older but open-minded people who keep up to date. Younger people aren’t necessarily the default better option. Think about all those times when a great person of our time died and you found yourself thinking that the world would have been better off if he or she had lived longer.

Personally, I think what matters is that people in certain positions, whether within government or a company, are the right people for the job. If they aren’t, old or young, they should be replaced by other people who are more fit, and, generally, there are more efficient and humane ways to do so than letting them get age-related diseases—for example, voting for someone else or hiring a different person. Granted, if the person to be kicked out is really powerful, this may well be easier said than done; however, when the holder of a position of such power dies of old age, his successor is rarely a nobody with no string-pulling abilities whatsoever. It’s not really a matter of longevity; rather, it’s that power attracts power, and I doubt that creating or not creating rejuvenation will make much of a difference in this respect.

Where does power come from?

It’s easy to hypothesize that a generation of rejuvenated 200-year-olds could end up becoming a gerontocratic elite that maintains power over younger people, but how would this be accomplished, exactly?

Maybe the older generation is rich and powerful, but unless we’re talking about a totalitarian world in which the masses are intentionally kept ignorant and poor, younger generations do have fair chances to make positions for themselves. Power and wealth come from knowledge, and, these days, knowledge is more freely and widely available than ever before.

Learning new professional skills and acquiring knowledge, in general, is possible for virtually everyone, thanks to the pervasiveness of educational media and the open availability of information on the Internet, including free (or reasonably affordable) online education projects, such as Coursera and Edx. The recent European initiative to ensure that all scientific papers are open access by 2020 represents another step towards a world that shares information rather than hides it.

Truth to be told, power and wealth don’t come only from knowledge; they also come from powerful and wealthy ancestors. If we didn’t develop rejuvenation, certainly all the Scrooge McDucks of the world would die sooner than they would otherwise, but their power and wealth would go to their heirs, and so on over the generations, which wouldn’t do much to prevent the creation of an elite. So, no, old age is not an easy way out of the problem of powerful elites ruling the world, and its absence wouldn’t make the problem any worse, really. The only possible way out is giving everyone equal access to knowledge and equal opportunities.

Inevitably, some will end up being more successful and thus more powerful than others anyway; however, if this allows them to become an oppressive force on the rest of us, I think this is a problem with our socio-economic system, not with the existence of lifesaving medical technology. I don’t know about you, but I’m not very keen on waiting until the “perfect” society or “perfect” economic system are built before we decide to cure the diseases of old age.

The fortune teller’s error

We shouldn’t make the mistake of predicting a negative outcome without considering the actual odds of it happening. I think fears of a society where rejuvenated elderly make younger people’s lives more difficult are misplaced in that they assume present-day scenarios will exist in the far future.

Take the concern about jobs, for example, rejuvenated old people would stick to their jobs forever and make it harder for young people to enter the workforce. It sounds bad, but there are a few assumptions behind it that we should question.

First, would rejuvenated old people actually stick to their jobs forever? Why? You hardly hear of a professional who was in the exact same job for forty years these days. More broadly, career change is a thing already. After all, after 40 years in the same line of work, it’s conceivable you might want to try something else, thus making room for others to take your place.

Will rejuvenated old people be allowed to stick to their jobs forever? Not everyone is a manager in charge of decisions, and your boss may well decide to lay you off, rejuvenated or not, and hire someone else.

Even if old rejuvenated people did stick to the same jobs forever, would they never take a break? Even if you’re in the prime of health, after a few decades, you may well wish to “retire” for a few years before going back to work, and your employer is probably not going to wait for you that long.

Will there be so many chronologically younger people in need of jobs in the future? The world population growth rate has been hopelessly corkscrew-diving for over 50 years now, and it is projected to keep going down as larger portions of the world transition from a developing to a developed economy. (In case you’re wondering, the population growth rate is going down not because more people die, but on the contrary, because fewer are born.)

Will people’s living depend on having a job in the future? We can’t expect indefinite life extension to happen very soon; before we can have 200-year-old people in the workforce, it’ll be at least a century. Is the economy going to be the same as today’s by then? Automation already seems on its way to cause the end of work as we know it.

I’d say it’s rather silly to oppose rejuvenation today for the reason that, in a century or two, it might cause an unemployment problem due to too many people being alive. It’s simply too long a time to make any even remotely accurate predictions on what the job market will be like or if there even will be any. In all honesty, I think it makes more sense to worry about a concrete problem that we already have today—the ill health of old age—than worry about a hypothetical one that might or might not happen in a hundred years’ time—massive unemployment. As time goes by, we’ll have a better picture of potential future problems lying ahead, and we’ll be in a better position than we are in today to do something about them.

Conclusion

I’ve said this many times over: the bottom line is always the same. Yes, life extension will most likely bring challenges along with benefits, but none of these challenges are certain, insurmountable, or not more than compensated for by the expected benefits. Let’s not deny ourselves and our descendants the chance for healthier, longer lives.

Date Posted: November 3, 2017

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Kurzgesagt – It Is Time to Talk About Curing Aging

The level of interest and support for rejuvenation biotechnology that targets age-related diseases is growing. Over the last few years, we have seen a significant increase in the number of popular science articles, news stories and research papers focusing on the idea that the aging processes are something we can target with therapies to prevent or cure age-related diseases.

With human clinical trials launched this year for senolytic therapies that remove toxic, aged senescent cells from the body, that interest level is only growing. Later this year, there are also going to be human trials for DNA repair, which has great potential for cancer and aging therapies. It is no longer a case of “can it be done” but “when will it be done” when it comes to bringing aging under medical control.

Bringing aging under medical control

You may remember the excellent video about aging that Kurzgesagt recently published on Youtube, where they explored what aging is and if science should do something about it in order to promote healthy longevity. We were pleased to have worked with Kurzgesagt to help create that video, and today, we are equally pleased to announce that a second video has been made in collaboration with them.

The video today takes a look at some of the most promising approaches that science is taking to address the aging processes. It covers removing senescent cells to improve tissue repair, increasing NAD in cells to increase DNA repair and improve cell function, and finally the amazing progress being made with stem cell therapies to combat diseases.

LEAF president Keith Comito, Vice President Oliver Medvedik, and other members of the team helped Kurzgesagt in the making of this video. We believe that bringing this topic to public attention now is very important indeed, especially if we take into account rapid population aging and the forecast that people aged 60+ will make about 1/3 of the global population by 2100.

The video today and the previous video by Kurzgesagt tie into our grand strategy. Last year at the DNA Conference in the Netherlands we were talking about engaging the wider public audience via popular YouTube channels and personalities and now we have begun to deliver on that promise.

Conclusion

Science is progressing in this area very rapidly, so it is important that we have these discussions now, before rejuvenation therapies arrive, so that we can promote equal access to these innovative medicines. Popular broadcasters such as Kurzgesagt are absolutely vital in helping to encourage public dialogue about the topic of aging. We would like to thank Kurzgesagt for this opportunity to work with them again, and we look forward to future collaborations.

Date Posted: November 1, 2017

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Rejuvenation Roundup October 2017

Today, we launch a new series on LEAF: the monthly roundup where we briefly discuss the latest news and articles about aging and rejuvenation from a number of different sources. We hope these roundups will be a great way to keep our readers in the loop.

Without further ado, let’s have a look at the highlights of the last month.

SENS Research Foundation and Spiegel Lab team up against glucosepane

This piece of news is a just a little bit older than one month, but I find it’s important enough to have a look at anyway. Cellular crosslinks are one of the factors driving human aging; they’re unwanted, accidental links between otherwise independently moving proteins, caused by the reaction of blood sugar and other molecules with the proteins themselves.

This binding causes the stiffening of the tissues of which crosslinked proteins are a part, which is really bad news, as this causes systolic blood pressure to rise and increases the risk of strokes with age, among other less-than-desirable ailments.

One of the most common crosslinks is glucosepane, a rather complex molecule that can be isolated only in very small amounts from the human body (and not even in a pure form). This limitation has made it hard for researchers to find ways to break glucosepane crosslinks because there was no easy way to test potential crosslink breaking molecules.

However, the Spiegel lab has managed to fully synthesize glucosepane and is using some of its derivatives in an attempt to create monoclonal antibodies that can seek and destroy glucosepane in the body. We’re looking forward to hearing more about it!

The arsenal against cellular senescence

Cellular senescence is a well-known hallmark of aging; while moderate amounts of senescent cells have a positive role in the body, their life-long accumulation eventually contributes to a number of age-related pathologies. Thankfully, senolytic drugs to selectively eliminate excess senescent cells are all the rage lately, and as Fight Aging! discusses in this article, several clearance methods are currently in development, while many others are to be expected, as initial successes for pioneers in this field will encourage further efforts from others. It’s certainly good to know that we might be spoiled for choice!

Dr. James Kirkland confirmed as a speaker at Undoing Aging 2018

As you might already know, Undoing Aging 2018, a conference on rejuvenation biotechnologies organized by Forever Healthy Foundation and SENS Research Foundation, will take place in March 2018 in Berlin, Germany. Early in October this year, Dr. James Kirkland has been confirmed as a speaker.

Dr. Kirkland is the director of the Kogod Center on Aging at Mayo Clinic, and he was the first researcher to publish a paper on senolytics. It goes without saying that he’ll be discussing cellular senescence, among a number of other interesting topics. LEAF representatives are also going to attend the conference and will hopefully get back with a set of interviews with the renowned researchers of aging!

Machine learning in tumor recognition

Machine learning is an important tool in research these days, as it allows researchers to quickly carry out extensive data analyses that would take months for humans. An exciting application of this technology, discussed in a previous article, is tumor recognition in magnetic resonance imagery of patients’ brains.

Professor George Biros of the ICES Parallel Algorithms for Data Analysis and Simulation Group recently presented the results of a decade’s worth of work on a machine learning system that can identify gliomas with impressive accuracy in a much shorter time it would take for human professionals.

Early and accurate detection of tumors, especially aggressive ones such as gliomas, is crucial for successful therapeutic interventions, and this kind of technology might well pave the way to a future where most, if not all, cancers can be busted before they have a chance to wreak havoc.

The Hallmarks of aging

Telomeres are probably the first things that pop into people’s heads when thinking about aging. The fact that telomeres shorten with age is well-known, while the existence of the enzyme telomerase and its role in replenishing telomeres is possibly a bit less known by the general public. If you’d like to learn a bit more about this particular hallmark of aging, it might be worth taking a look at this concise but clear article on Geroscience.

Since we are on the topic of hallmarks, let’s have a look at Steve Hill’s summary of the genomic instability hallmark. In a nutshell, this is essentially an accumulation of DNA damage that can occur in several ways—exposure to radiation or chemicals, for example, or even during normal cell replication. The results of genomic instability are many and not too pleasant; it can lead to cell dysfunction, cellular senescence, or even cancer. Thus, to fully address age-related diseases, we will need means of DNA repair that solve this problem, and while we’re not there yet, some potential solutions are in the works.

FA! announces the 2017 winter fundraiser for SENS

There are two downsides to scientific research: it isn’t super cheap, and it won’t carry itself out. This is why ensuring sufficient funding is crucial to the development of rejuvenation biotechnologies, and crowdfunding initiatives are a big part of this. Like every year for a while now, FightAging! is running a winter matching fund for SENS Research Foundation.

Together with other generous folks, FA! has put together a $36,000 fund to match SENS patrons’ donations for the next year in an attempt to help SENS reach the goal of $250,000 to finance several ongoing research projects at the Buck Institute and other laboratories. This is good news if you’re a SENS patron because your donations will be matched; if you aren’t, I guess this is a moment as good as any to consider becoming one!

Life Extension discussed by popular YouTubers

Life extension and rejuvenation biotechnologies need the support of a large community to really take off; a first, important step to reaching a wider public has been taken in the second half of October this year, when some of the big guns of advocacy have been fired for the first time: popular YouTube channels Kurzgesagt, CGP Grey, and Thunk have all published videos discussing and advocating for the possibility of putting an end to aging.

Combined, these three channels have over 8 million subscribers, and chances are good that other famous channels will follow suit and publish their own videos on the topic, reaching an even wider audience. In particular, I’m pleased to say that the Kurzgesagt’s video was created with the help of LEAF president Keith Comito, and I’m sure I speak for everyone here at LEAF when I say that we are all looking forward to further collaborations with Kurzgesagt!

Conference “Motivation to life extension” and other events in Moscow

On October 14 LEAF Director Elena Milova gave a talk at the conference “Motivation for life extension” co-hosted by the Foundation Science for Life Extension and Singularity University Moscow Chapter. Elena shared with the audience her views regarding the evidence-based approaches to increase adherence to healthy lifestyle and high compliance. One of the best systems to effectively change one’s behavior to a more longevity-friendly is described in the book Influencer: The New Science of Leading Change that Elena is recommending you to read.

Later in October, the same partnership organized a lecture of the famous biohacker Serge Faguet, and Elena managed to get back with an interview with Serge.

MouseAge is funded!

Finally, we are delighted to announce that the MouseAge project at Lifespan.io reached its initial fundraising goal, and is now moving forward to the stretch goal.

Thanks to the devotion of the team, the work on the creating the application has already begun. Soon, a beta version of the application will be made available to backers via the Apple Store, allowing them to start using it in the lab and contributing to scientific progress.

We would like to thank everyone in the community who has supported the project and a special thank-you to investment mogul Jim Mellon and Bill Gelpi from Rocket games for their donations.

Coming up in November

The Lifespan Extension Advocacy Foundation, in collaboration with the Moscow Chapter of Singularity University, and consulting group Deloitte, is hosting an expert discussion in Moscow on how to inform the public about the potential of rejuvenation biotechnology. These experts believe that by raising awareness of new medical technologies to prevent aging, it could help to increase support for defeating age-related diseases and increasing the healthy period of life.

The panel discussion “6 ways to talk to people about ending aging” will bring together famous futurists, scientists, science popularizers and public figures who foster the dissemination of the idea to prevent aging in Russia and other countries, such as Jose Cordeiro (director of Humanity Plus), Valerija Udalova (director of Russian cryonics company KrioRus), Eugeny Kuznetsov (ambassador of Singularity University in Russia) and others.

Elena Milova will be moderating this discussion together with Jin Kolesnikov, co-founder of Singularity University Moscow Chapter. If you happen to be in Moscow on November 4, you are welcome to attend this event – please don’t forget to register and bring an ID with you.

Date Posted: November 1, 2017

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Journal Club October Video Available

We have been talking about a number of new studies in past Journal Clubs, so we thought it was time to get into some aging theory. We chose to cover one of the most cited and highly regarded damage theories of aging in this edition of the club.

In this edition of Journal Club, we continued discussing the Hallmarks of Aging, one of the most popular aging theories and based on a damage repair based approach to the damage aging causes.

López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

Thanks to our guests Dr. Laura Weston, biologist Sven Bulterijs and Lifespan Heros Joel Peterson and Bill Gelpi for joining us for the show.

Date Posted: October 31, 2017

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Serge Faguet – Interview with a Biohacker

Serge Faguet is a Russian entrepreneur, the owner of a profitable travel company, Ostrovok, and the founder of several tech startups, including a new secret, AI-related one in Silicon Valley. For the last few weeks, his name has been all over the internet because of the article “I’m 32 and spent $200k on biohacking. Became calmer, thinner, extroverted, healthier & happier.”

While his goals are without a doubt desirable (who would not want to be healthier and happier?), some of the public, including medical specialists, have received his story with some skepticism. On the other hand, those who support the idea of healthy longevity believe that Serge is a role model whose example should be taken seriously by each and every person.

LEAF Director Elena Milova attended a conference in Moscow, where Serge had been invited to talk about his system in more detail. After the event that was jointly organized by Mikhail Batin, the lead of Foundation Science for Life Extension and Open Longevity ICO, and Jin Kolesnikov, the co-founder of Singularity University Moscow Chapter, Elena had an opportunity to talk to Serge face to face. Today, we share with you his interview and commentary regarding his approach to health management.

Before our quick overview of Serge’s system, we would like to remind you of his principles for creating his approach to health and longevity. Here is the list from Hackernoon, where his article was published:

“In all these areas I use roughly the following framework to decide regarding specific tactics:

Is it scientifically sound? (i.e. are there studies if such are feasible?)
Is it logically sound? (i.e. is there a sound explanation behind the tactic?)
Is the estimated cost (risk, money, time/energy) worth the estimated benefit?
Do independent smart experts (e.g. doctors) agree with the approach?
Do they actually practice the approach themselves and with their families?
Do I track my objective/subjective metrics related to the tactic, if feasible?”

Relying on these principles, Serge has created his own personalized health and longevity strategy, which focuses on six key areas he has identified as important.

Sleep Hygiene

Serge believes that getting plenty of restorative deep and REM sleep on a regular basis is a key component in maintaining good health. Sleep is essential for the human body to repair and recover from injury, and there is plenty of evidence to suggest that a constant lack of sufficient sleep can lead to devastating consequences to health.

He monitors his sleep quality using the ŌURA health wearable device, although there are many others on the market to consider. Recording your health data and monitoring it over time is essential in properly managing your personal health and ensuring that the steps you are taking are effective.

Take steps to eliminate blue light sources three to four hours before sleep, as this wavelength of light is known to interfere with sleep. Studies have demonstrated that exposure to blue light can increase alertness[1-4] and can also stimulate cognitive functions[5-7]. Also, a recent study reported that exposure to blue light-emitting e-readers at bedtime may negatively affect sleep and the circadian system[8].

If you must use an e-reader or cell phone before sleeping, you may wish to consider a blue light filter, and some of them are available for free, though it must be said that, currently, the scientific evidence supporting them is just not there yet. However, you may wish to see if it works and improves your sleep, which is all the more reason why you should be monitoring your sleep quality and other biomarkers.

Another simple measure you can take is to reduce light pollution using heavy curtains that block light from outside or, failing that, a sleep mask to achieve the same outcome. If you have other light sources in your bedroom, such as LED clocks, cable TV boxes and other electronics with lights on them, cover the lights or remove them from the room completely.

Serge suggests to keep the room cool and humid between 18-19 Celsius, as being too warm can make sleeping difficult or reduce sleep quality.

Optimal Nutrition

Serge aims to eat a diet that keeps insulin levels stable, increases glucose disposal and optimizes growth factors, such as IGF-1 and mTOR, towards positive things like muscle growth and tissue repair and away from inflammation and cancer. He also avoids refined sugars, bread, pasta, fruit juice, candy, chocolate and other foods that have a high glycemic index and can cause insulin levels to spike.

He eats a mainly plant-based diet, and when buying animal products, he only buys organic, as cheaper food is frequently of lower quality and may have had harmful shortcuts taken to reduce the cost. From a nutritional perspective, it would probably be better to eat a small quantity of expensive, high-quality meat than a large quantity of cheap, low-quality meat.

Serge also avoids salt, as it raises blood pressure, and alcohol, which he believes can disrupt sleep.

Optimal Exercise

For his approach to fitness, Serge seeks to maximize metabolic benefits, such as hormones and insulin sensitivity, minimize the time spent exercising, and reduce the risk of injury.

To make the most of his time, he engages in high-intensity interval training (HIIT), a form of interval training that alternates short periods of high-intensity anaerobic exercise with lower-intensity recovery periods. In HIIT, one repeatedly alternates between a short burst of high-intensity exercise and a brief period of low-intensity activity until too exhausted to continue. Typically, HIIT sessions tend to last 30 minutes or less, though that time varies by fitness level.

Serge is also mindful to avoid long periods of sedentary activity, and sitting for long periods is well known to be harmful to health. Using standing desks or taking frequent breaks to walk around and stretch reduces the impact of sitting too much.

Mental Health

Serge believes that mental health is a key component of health and longevity, so he aims to maximize stress resilience, increase social support and foster a sense of purpose while avoiding negative emotional states.

In order to achieve this, he uses a combination of meditation and psychotherapy while avoiding lying and falling into other negative habits. Mental health is very important to well-being, and it is not something that should be neglected. There is some scientific data that suggests a small but positive effect of meditation on the length of telomeres[9].

Another set of data indicates that meditation may help to regulate the activity of certain brain cells that help to clear waste, which is possibly a way to postpone Alzheimer’s and other cognitive pathologies with age[10].

Medical Testing

When practicing a personal health and longevity strategy, everything you do could be meaningless. If you are not recording your health data, monitoring biomarkers and adjusting your approach based on this data, then what you are doing is faith-based medicine, not science. Taking drugs and supplements without keeping close watch on how they are affecting your body is not the way to optimize your health.

Serge uses many metrics to evaluate his approach, including DNA tests, blood tests, and sleep monitoring. He has a huge list of biomarkers he considers important and goes into detail here. Even if you cannot do hundreds, there are plenty of easy and cost-effective metrics you can and should be using to monitor your health.

Once you have an accurate picture of your health, you can then optimize and change your approach to see what works best for you. Methodical and scientific evaluation is the key to developing your health and longevity strategy.

Supplements and Drugs

Serge aims to improve his health and cognitive function through the use of drugs and supplements that have at least some level of scientific support.

He takes metformin, a diabetes drug that lowers blood sugar without causing hypoglycemia. Some data suggest that it may be beneficial in preventing cancer and heart disease, though, at this time, this is still unclear and more studies are needed. Other things, such as vitamin D, vitamin K2, group B vitamins, quercetin, magnesium, and melatonin, seem to have potential health benefits when applied in amounts prescribed by a medical advisor.

He takes a variety of supplements and hormones as part of his approach, although he is keen to stress the need for performing research before the start of a regimen.

Elena Milova’s commentary

During the lecture, I asked Serge if he had spent most of his money on treatment, diagnostics or something else. He said that the lion’s share went to analysts and medical advisors, whose job it was to consider each and every drug, supplement, therapy, and lifestyle measure that he was intended to implement.

Serge literally hired the best possible scientists in each relevant field to help him find out what would work well and what would be safe in his particular case. Yet, when making the final decision on whether he should take each measure or not, he studied the accumulated materials himself. Looking at how easily he can name biomarkers, symptoms and specific genes related to metabolic regulation, I believe that he learned quite a lot during this journey.

I find this fascinating. This amount of responsibility for one’s health is so rare! How did Serge manage to remain motivated to learn for a long period of time and acquire such self-discipline? He said that people should be passionate about what they do. Genuine passion will keep you inspired and keen to overcome obstacles until you reach the goal. If this is the influence of an entrepreneur’s mindset, I ask myself if we all should adopt it in order to become such daring managers of our own health and longevity.

Literature

[1] Lockley, S. W., & Gooley, J. J. (2006). Circadian photoreception: spotlight on the brain. Current Biology, 16(18), R795-R797. [2] Viola, A. U., James, L. M., Schlangen, L. J., & Dijk, D. J. (2008). Blue-enriched white light in the workplace improves self-reported alertness, performance and sleep quality. Scandinavian journal of work, environment & health, 297-306. [3] Rahman, S. A., Flynn-Evans, E. E., Aeschbach, D., Brainard, G. C., Czeisler, C. A., & Lockley, S. W. (2014). Diurnal spectral sensitivity of the acute alerting effects of light. Sleep, 37(2), 271-281. [4] Najjar, R. P., Wolf, L., Taillard, J., Schlangen, L. J., Salam, A., Cajochen, C., & Gronfier, C. (2014). Chronic artificial blue-enriched white light is an effective countermeasure to delayed circadian phase and neurobehavioral decrements. PloS one, 9(7), e102827. [5] Vandewalle, G., Gais, S., Schabus, M., Balteau, E., Carrier, J., Darsaud, A., … & Maquet, P. (2007). Wavelength-dependent modulation of brain responses to a working memory task by daytime light exposure. Cerebral cortex, 17(12), 2788-2795. [6] Vandewalle, G., Schmidt, C., Albouy, G., Sterpenich, V., Darsaud, A., Rauchs, G., … & Maquet, P. (2007). Brain responses to violet, blue, and green monochromatic light exposures in humans: prominent role of blue light and the brainstem. PloS one, 2(11), e1247. [7] Daneault, V., Hébert, M., Albouy, G., Doyon, J., Dumont, M., Carrier, J., & Vandewalle, G. (2014). Aging reduces the stimulating effect of blue light on cognitive brain functions. Sleep, 37(1), 85-96. [8] Chang, A. M., Aeschbach, D., Duffy, J. F., & Czeisler, C. A. (2015). Evening use of light-emitting eReaders negatively affects sleep, circadian timing, and next-morning alertness. Proceedings of the National Academy of Sciences, 112(4), 1232-1237. [9] Thimmapuram, J., Pargament, R., Sibliss, K., Grim, R., Risques, R., & Toorens, E. (2017). Effect of heartfulness meditation on burnout, emotional wellness, and telomere length in health care professionals. Journal of Community Hospital Internal Medicine Perspectives, 7(1), 21-27. [10] Wells, R. E., Yeh, G. Y., Kerr, C. E., Wolkin, J., Davis, R. B., Tan, Y., … & Press, D. (2013). Meditation’s impact on default mode network and hippocampus in mild cognitive impairment: a pilot study. Neuroscience letters, 556, 15-19.

Date Posted: October 30, 2017

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Neutrophils are a Key Player in Nerve Regeneration

The potential of the immune system to help repair tissue, including for peripheral nerve damage, Atherosclerosis, and Parkinson’s is considerable. Immune cells not only fight infection; as this new study shows, they also help the nervous system remove debris, paving the way for nerve regeneration following injury.

While previous studies suggested that nerve cell damage repair was conducted by other immune cell types, such as macrophages, researchers from Case Western Reserve University School of Medicine have shown that neutrophils also play a role.

What are Neutrophils?

Neutrophils are white blood cells created in the bone marrow, and they are normally the first responders to attack and injury. At the first sign of microbial invasion, they head to the site of injury as quickly as possible so that they can destroy the invaders. This is good, as it means that the body can mount a rapid defense the moment there is an infection, helping us to fight off illness and injury.

A new role for neutrophils

In the new study led by Dr. Richard Zigmond, the team discovered that damaged nerve cells produce a signals to summon neutrophils to the injury site in mice. Damaged sciatic nerves in the mice produced two signals to call in the neutrophils, Cxcl1 and Cxcl2; the levels of these signals were hundreds of times above what is normally produced in healthy cells.

Once the neutrophils arrive at the injury site, they engulf the cell debris that resulted from nerve damage, and they leave the area clean so that the cell can repair itself. The process is critical, as cells cannot repair properly if the injury site is not clear, and without neutrophils, nerves will not regenerate properly after being damaged.

Previous studies have suggested that macrophages are the most important immune cell for engulfing cell debris and clearing up the injury site around damaged nerves. The team had been studying injuries in engineered mice that lack a receptor on the surface of macrophages – CCR2 – which helps macrophages locate injury sites. They expected that in these mice, cell debris clearance following nerve injury would be dramatically reduced, but they were surprised to find it was unchanged. This was a real mystery that the team set out to solve.

They drew up a list of other types of cells that might be compensating for the loss of the macrophages and launched multiple tests to see which cells were picking up the slack. They created experiments to test this, including sorting immune cells found at injury sites by the molecules on their surfaces. They discovered that several different immune cells compensate for the lack of macrophages, so there is clearly considerable redundancy built into the system. The team also determined that the greatest contributor of these various cells to the removal of debris were neutrophils.

The researchers also found that if they depleted neutrophils, the level of nerve clearance was significantly reduced in both normal mice and the mice lacking macrophages. This means that, without neutrophils, nerve cells could not clearly cell debris properly even if macrophages were present; this strongly suggests neutrophils are of primary importance here.

Conclusion

This discovery could pave the way for new therapies designed to repair nerve cells damaged by neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. The clearing of cell debris following nerve injury is critical for proper repair and nerve regeneration, and this study has discovered the role of neutrophils in this process.

The potential for targeting neutrophils to boost the clearing of debris to promote nerve repair is obvious and could be achieved via the use of immunostimulant molecules, which are commonly used to treat chronic infections and immunodeficiencies.

The next step for the team will be to explore immunostimulant molecules and the relationship between neutrophils and other cells in the nerve regeneration process. The immune system is increasingly looking like it holds the key to effective tissue regeneration, and science is rapidly unlocking the secrets of these amazing cells.

Literature

[1] Lindborg, J. A., Mack, M., & Zigmond, R. E. (2017). Neutrophils are critical for myelin removal in a peripheral nerve injury model of Wallerian degeneration. Journal of Neuroscience, 2085-17.

Date Posted: October 24, 2017

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The Societal Benefits of Rejuvenation Biotechnology

Recently, we have explored the benefits that rejuvenation biotechnologies promise to bring to ourselves and the people close to us. I would imagine that most people have no difficulty acknowledging these benefits, but even so, many people tend to focus on potential large-scale downsides of rejuvenation while neglecting entirely its benefits on society at large.

The following is a brief discussion of how, in my opinion, anti-aging biotechnologies would positively impact the whole of humanity—assuming they were widely employed, as they should be.

Doing away with useless expenses

The reason retirement exists is simple: older people aren’t healthy enough to work and support themselves, so the State needs to pay them pensions. Expenditures for pensions have no other real utility than allowing old people to live decently; this is, of course, a noble goal in and of itself, but if old people were able to support themselves, it would be better for them—because they would enjoy a large degree of financial independence—and also for the State and thus society—because the money saved on pensions could be put to other uses.

Let’s also not forget that, as their health keeps deteriorating, older people need ever-increasing medical attention. Unfortunately, geriatric medicine isn’t able to restore their health or prevent it from worsening, thus it becomes less and less effective with the passing of time. All that can be achieved through geriatric medicine is modestly reducing suffering or postponing the inevitable; in this sense, expenditures for geriatric care are nearly useless.

What would happen if rejuvenation biotechnologies to stave off age-related diseases were widely available?

For one, older adults would enjoy more youthful health; in a best-case scenario, people could look forward to enjoying the same health as typical young adults irrespective of their actual ages. Naturally, we can’t expect age-related diseases to be fully eradicated overnight; rather, we should expect a gradual series of advances staving them off by longer and longer measures, until they will possibly be eradicated altogether. Accordingly, the need for geriatrics will gradually decrease and eventually disappear, together with the medical expenditures associated with it. I don’t suppose I need to make a case about how not having to pay for treatments that can’t make people healthier anyway is better than the opposite—and again, the money saved on geriatrics could be put to other uses; for example, it could be used to finance State-subsidised rejuvenation therapies.

Secondly, if rejuvenation biotechnologies gradually made people healthier for longer, and perhaps even for an indefinitely long time, then people’s ability to work would be preserved accordingly. This would translate into more wealth contributed to society and less wealth spent on pensions; people who work for longer can pay taxes for longer and don’t need State support for longer. This would certainly change the way social security works, but I guess pensions wouldn’t disappear altogether—there might be other things that make you unfit for work, and after thirty years of working, you might want to take relatively short break, and it would be nice if we gave everyone the chance to do so by granting them a pension for maybe a couple of years.

The idea of working for a longer time, perhaps even much longer, may sound unappealing to some. To be honest, if the choice was between working for only 30 to 40 years because then I’d be too sick to continue and working for 80 years always in good health, I’d definitely take the latter. Besides, if I disliked my job too much to want to do it for such a long time, I would most definitely not consider shortening my life to shorten the time spent in that line of work; simply changing my job, however easy or difficult it may be, seems more reasonable.

Speculations on how this all might work in the distant future would be a pointless exercise because we don’t really know how much different that future will be, and they would be outside the scope of this article anyway. All that matters is that, in the near future and today’s economic system, it would definitely be a good thing for everyone if we could save on pensions and geriatrics.

Transforming society for the better

It’s impossible to predict with certainty the effects of any disruptive technology over the long haul, but a concern granted to be voiced in a discussion about rejuvenation is that of social stagnation—i.e. the default assumption that old people hanging around for longer would hold back social progress because of their ‘old people mentality’.

Here I will not try to argue against the concern above; rather, I’m going to put forward the opposite scenario, one that not many seem to consider: society could benefit from longer-lived members. I’m not talking just about scientists or great thinkers who could actually speed up our progress on all fronts if they just had more time at their disposal; I’m talking about a population with ever-growing life experience, knowledge, wisdom, and a lot to teach to younger generations. (Just imagine how much better a parent you could be with a 120-year life experience as opposed to 30, for example.)

In my opinion, this scenario is even more plausible than its opposite, because there’s no real evidence that very long-lived yet physically and mentally perfectly healthy people would necessarily be conservative fossils just because they’re old. Yet, the gloom-and-doom scenario is often people’s first thought. I have a hunch that this might be just evolution at work, as an extra pinch of pessimism might have granted better survival chances than too much optimism back in the day, but I don’t want to stray from the topic.

Another possible beneficial side effect of longer lifespans might be improved foresight. It’s easy to neglect global concerns that might not affect us personally over the course of our 80-odd-year lifespans. Some of us do display sensible behavior and are worried about the kind of world we’re going to leave to the humanity of the future; yet, others don’t concern themselves with problems that might manifest only long after they’ll be gone.

However, if our lifespans were much longer than just 80 years, the consequences of our negligent behavior would stand far better chances of catching up with us; this might make even the least sensible of people think twice before behaving irresponsibly, and all of us would benefit from it.

Sure, it would be commendable if everyone was genuinely concerned about pollution, for example, for the sake of humanity as a whole rather than just for their own sake; however, regardless of individual motives, the end result would still be a better world for everyone. I guess we could be content with that, even if some of us contributed to it because they had personal stakes and not exactly out of the kindness of their hearts.

Date Posted: October 23, 2017

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The Discord Life Extension Server

We have been hard at work advocating, writing and supporting the development of life extension technologies, or as we call them, rejuvenation biotechnologies. During the course of our activities, we have found that many people new to the topic have lots of questions and are naturally curious about the science behind it.

As great as giving talks at events and shows about life extension is, nothing beats talking to people one-on-one so that they can share with us any concerns they may have, or ask questions that might be on their mind.

A place to be among like-minded people

Since we began we have been very keen to interact with people on a personal basis and foster an active and engaged community. To that end, we decided to create a life extension discord community where our fellow supporters of rejuvenation technologies and all people interested in science can meet and get to know each other. To us, this is also a place where we can be among like-minded people and rest from that constant pressure of a mainstream culture that life extension supporters often have to bear with.

We had already been using Discord operationally to coordinate LEAF/Lifespan.io activities (and it is great!), as well as in our personal lives for video gaming, so we knew it was a solid platform. With the recent introduction of video chat adding to the wealth of supported features it made sense to make Discord the home of life extension discussion. You can find our Discord life extension server here, and you are welcome to join us!

We have regular discussions about rejuvenation biotechnology, gerontology, aging, longevity, life extension, radical life extension, immortalism, how to extend our own healthspan, what geroprotectors to take, and other related topics. Yes, there are no restrictions on your ambitions or your desire to learn, we talk about all kinds of things that you might wish to discuss (including policies but not politics!) there. We are also planning some cool live events in the future too.

A place to get more involved

As well as discussion and events there is also the opportunity to get involved and join in with our activities and even become a volunteer. We sometimes post our “10 minutes to help Lifespan” activities that anyone can help with. If you are interested in taking a more active role in advocating for science while also acquiring new skills and testing your capacities in a new field, the friendly atmosphere on our Discord life extension server will help you begin.

We also share our views with our Discord community on the best approaches to engage and inform those new to the topic, discussing ways to speak with people about the typical concerns related to longer lives, from immortal dictators to overpopulation, and issues with human rights.

These tips might make your life a bit easier and could help you turn your friends into supporters. We believe that the more minds that are engaged in finding the path to healthy longevity for all, the better, and we are here to support you!

The Discord life extension server is the ideal place to introduce yourself, get to know the LEAF team and see how you might like to get involved, so what are you waiting for? Come and join us today!

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The Blog

Building a Future Free of Age-Related Disease