Will Increased Lifespans Be Only for the Rich?

Some people think only the rich will afford life extension.

Date Posted: March 26, 2017

The concern that rejuvenation biotechnologies might cause social disparity and further widen the gap between rich and poor is one of the most commonly raised ones, probably second only to concerns of overpopulation. Like many others, this concern may appear valid at first, but it does not survive careful analysis.

Anti-aging sticker shock

The underlying assumption of this argument is that rejuvenation therapies would be so very expensive that only rich people would be able to afford them, thus fracturing the world into ever-young, ever-healthy rich people and the poor, sick, old people with no access to these technologies. It is very likely that rejuvenation therapies will be quite expensive (at least initially) due to a number of factors.

However, before we delve deeper into the details of this discussion, let’s remind ourselves of an important but possibly understated fact: rejuvenation biotechnologies are life-saving medical treatments that are meant to prevent age-related diseases and allow people to maintain good health throughout their lives. In this sense, they are no different from antiviral or cancer therapies, which are currently prescribed and administered by doctors in appropriate healthcare facilities. So, just the same as any other life-saving treatments, the price is irrelevant in the face of the benefits that they would confer to us, and it is certainly not a valid reason not to develop them.

However, even if we can initially assume a high cost for rejuvenation biotechnologies, we need to keep in mind that new technologies generally start off as very expensive and eventually become affordable and widespread. For instance, it took only 15 years for the full genome sequencing cost to drop from $100 million to $300, making personalised medicine reality globally.

Fig 1. The Cost of Sequencing a Human Genome change, 2001-2015. Source: National Human Genome Research Institute

In the field of medicine, there are several other examples of this same trend of falling cost and prices. The drug metformin, which is used for the treatment of type 2 diabetes (and probably the first drug to slow down aging in healthy people, which is currently the subject of the TAME clinical trial), was initially expensive but eventually its price plummeted to a few dollars. Its price fell from $1.24 per tablet in 2002 to 31 cents in 2013. The infographic below shows some other examples of drugs that were once expensive and have subsequently fallen in cost.

Similarly, improvements in technology have drastically reduced the costs of research diagnostics, and the advent of remote technology has allowed a cost reduction for both patients and hospitals, as specialists can be contacted at a distance. For example, hospitals do not need to have radiologists on location all the time. Instead, they can instead remotely send them patient data for analysis and thus only pay for each individual service; this, in turn, implies potentially cheaper services for the patients as well.

Even gene therapies, stem cell therapies and immunotherapies may soon become cheaper, less time-consuming, and consequently more widely available thanks to innovations such as this new semi-automated benchtop system, which produces modified cells in sufficient numbers very rapidly at lower cost, or automated systems for cell therapies and immunotherapies with similar production streamlining and potential cost reduction [1-5].

Outside of the field of medicine, a classic example of dropping prices is that of computers and electronics. At the beginning of the computer age, computers were huge pieces of machinery with very limited capabilities, and only few institutions in the world could afford having a few of them at best. However, as technology improved, the production of computers (and that of electronics in general) has become easier, cheaper, and more efficient, to the point that today we all walk around with tiny computers—smartphones—in our pockets, and these computers are hundreds of times more powerful than those used by NASA to send the first people on the Moon.

Similarly, cars used to be too expensive for an average person to afford. Today, not only are cars ubiquitous and largely affordable, but even the newer, cutting-edge electric cars (for example, Tesla cars) are reaching the same price range as regular cars, despite being relatively new on the market. Another example of the high-tech sector is that of 3D printers. A mere decade ago, a 3D printer cost around $100,000; today, one can buy a good 3D printer for less than $500—a price drop of 95.5%.

Even more interestingly, this trend extends further to other areas of technology, such as the food industry. In 2013, the first lab-grown burger cost $325,000; a mere two years later, the cost had dropped to around $11. Even though the company estimates that it would take two decades to turn the burger into a viable product, other companies have recently shown confidence that this can be achieved on a much shorter time scale.

For example, SuperMeat hopes to have its first lab-grown meats available in stores in only five years, for the same price as regular meat or less. All of these examples show that technology typically becomes much cheaper as time goes by; there is no reason to believe the same would not be true of rejuvenation technologies, especially when one takes into account an extremely strong economic motivator.

Rejuvenation would be the largest industry in history

The market for rejuvenation biotechnologies would be the largest in history, and, indeed, some investors, such as billionaire investment expert Jim Mellon, are already taking notice. Every single person in the world is aging and is thus a potential customer. It is of course very likely that people who have wealth, and therefore greater means, will obtain cutting-edge technology first (as we have seen repeatedly throughout history) before everyone else. This has always been the case, and it has always been that, shortly thereafter, such technology and access has become widespread.

However, one should consider that those early adopters are playing “guinea pig” and, in effect, are paving the way for the masses and helping developers offset the costs incurred during development, as they are paying premium prices for early access to these technologies.

Socio-economic considerations

If, for the sake of argument, we assume that rejuvenation biotechnologies could somehow be an exception to the trend of falling prices in technology, we would need to decide whether people ending up paying for their own rejuvenation therapies is more of a realistic scenario than governments subsidizing the treatments, partly or wholly.

The majority of countries in the world have universal healthcare systems that take care of their citizens’ or residents’ health needs either for free or for a nominal fee. These costs are offset by taxes, which ensure the health service is able to provide this level of care to all.

Fig 2. 2009 Countries with universal Healthcare Source: wikimedia

Other countries, particularly the United States, do not have a universal healthcare system; citizens or residents of such countries generally have private health insurance to cover their medical expenses, and the coverage of each insurance plan may vary substantially, depending on what each individual subscriber can afford.

In many ways, aging can be considered to be a chronic, progressive, and fatal disease (indeed, some researchers do [6]) of the type that insurance companies would likely not be willing to pay medical expenses for. However, we should take into account that its progression is remarkably slow. It generally takes decades for age-related diseases to manifest, so it would probably make little sense for people under forty years of age to include rejuvenation treatments in their health insurance. As a matter of fact, the very nature of the problem may call for an entirely different insurance strategy.

Presently, insurance policies are drawn up to cover the cost of potential risks that might lie ahead; this is the very reason why more likely risks make for more expensive policies and vice-versa. One is not guaranteed to get all age-related diseases—simply because one or few of them manage to kill us before we can get the others—but comprehensive, preventative rejuvenation necessarily needs to address all aspects of biological aging that may lead to any such ailments; in this sense, aging is a disease that we all suffer from, and we will all suffer from each of the age-related diseases if we live long enough.

Therefore, aging is not a potential risk but rather a certain fate that will strike each of us differently, depending on individual circumstances. While the market share of each insurance company offering rejuvenation policies would be huge, such policies could not logically treat aging in the same way they treat potential risks. An insurance company will pay for a customer’s stolen car—or medical expenses for a certain disease—if and when the car has been stolen—or when the disease has struck.

However, aging is a lifelong process that needs to be addressed in a preventative fashion [7] [8]; at no specific point could we say “aging has struck the patient now, but not before.” This suggests that private insurance may not the be right way to go; instead, we should consider this matter from the point of view of the government.

Health costs in the current system are unsustainable

Health expenditures for the elderly currently constitute a considerable burden on a country’s economy. Although the elderly have already contributed wealth to society when they were younger, they often stop doing so when they retire. Furthermore, they receive a pension from the government and will do so for the rest of their lives. While, in theory, pensions should already have been paid for by the elderly themselves with their work earlier in their lives, things are quite different in practice, and some countries are already increasing the retirement threshold further.

This is an unsustainable strategy, because barring radical interventions—such as rejuvenation therapies—there is a point past which elderly people simply are not healthy enough to work. As a matter of fact, the cost of medical expenses for the elderly grows dramatically each year, and it is also to be noted that geriatric treatments lead to no significant results, both in terms of overall individual well-being and fitness for work, and they become increasingly less effective as the patients grow older. As a result, most individuals produce no wealth and their deteriorating health causes increasingly significant expenses during the last year or two of life and further strain on the economy [9].

The desired result of rejuvenation therapies leads to a much better scenario. If rejuvenation therapies are reapplied with proper timing, no individual would ever reach a state of age-related decay and poor health that could make him or her unfit for work. Consequently, the costs of treating age-related diseases using current medicine could be reduced with the arrival of more robust therapies offered by rejuvenation biotechnology. Such rejuvenation therapies aim to prevent a plethora of diseases before they manifest, potentially saving money. However, even if the costs are the same and we are simply trading one set of medicines for another, the benefit to health, quality of life and productivity makes it more than worth it regardless.

Retirement and increased lifespans

When considering retirement in relation to rejuvenation biotechnology, we should consider the two possible scenarios that may arise. The first scenario is the simple increase of lifespan beyond the current limits – this could be a few years or even a decade or two of healthy life. The second scenario is that of negligible senescence, in which medicine allows indefinite lifespans via periodic repair of the various damages and dysfunctions aging causes. Let’s take a look at both of these possibilities and consider the benefits and changes society may encounter as a result.

Scenario 1: Increased lifespans. In a situation where additional healthy years were added to the human lifespan, an immediate benefit to society would be that people could retire later in life and continue to contribute economically and remain productive for longer. This would reduce the costs of pensions and help bolster the economy. Ultimately, in this scenario people would still retire as they already do, but later in life and with more healthy years to enjoy.

Scenario 2: Negligible senescence. In the more extreme case of negligible senescence, people would, in principle, be able to work indefinitely, regardless of their age, thus producing wealth nearly constantly. For this reason, retirement would likely change from a permanent cessation of working to the need for a break longer than a normal holiday, perhaps similar to a long-term work sabbatical. Pensions might even become optional, with workers taking sabbatical breaks from work that could last for years, allowing people to retrain and reinvent themselves.

Another remarkable benefit would be that the government would see drastically reduced costs, which are traditionally spent on pensions, as people would no longer retire in the traditional sense. It might be the case that the government would perhaps replace traditional pension schemes with sabbatical or UBI schemes to allow workers to accrue money over time to take such a break from work. If the State did not do this, then private enterprise might provide such a service.

In short, this second scenario has the potential to turn the current situation on its head—we would go from having high morbidity of age-related diseases that disable the elderly preventing them from being productive and causing major public expenses, to having productive elderly who contribute to the economy and whose health needs are little-to-no burden on it.

It’s easy to see how it would be far more convenient for any given State to pay for the periodical rejuvenation treatments of its citizens rather than maintaining the current state of affairs.

Apart from economical considerations, we must also keep in mind that, as said, rejuvenation therapies are life-saving medical treatments that prevent age-related diseases from ever manifesting. As such, ensuring their development and widespread access is among the objectives of WHO, according to its Constitution. The WHO Constitution says that each government is responsible for the health of its residents, and the attainment of the highest health standards is the very objective of WHO itself.

The WHO definition of ‘health’ is a ‘state of complete physical, mental and social well-being and not merely the absence of disease or infirmity’. Rejuvenation therapies match this definition perfectly: they would eliminate age-related diseases entirely and enable people to enjoy a normal life regardless of their age, without the limitations currently imposed on the elderly by their constantly declining health. They would improve the physical, mental, and social well-being of all people.

The WHO Constitution further states that ‘[t]he enjoyment of the highest attainable standard of health is one of the fundamental rights of every human being without distinction of race, political belief, economic or social condition. In other words, because of the health standard improvements they would cause, rejuvenation therapies would be a basic right of everyone, and both local governments and WHO would have a responsibility to do all in their power to make sure this right is respected. (As a side note, this last paragraph of the Constitution would be better if it said that no distinction of age should be made either).

If not everyone can have it, then no one should have it?

Thus far, we’ve argued that while rejuvenation therapies may well be expensive at the beginning, they would be government subsidized and would likely become cheaper and cheaper as the underlying technology improves. However, what if this prediction were wrong?

If everyone was supposed to pay for their own, expensive rejuvenation, then being indefinitely young would indeed be only for the rich, and the rich-poor gap would become even worse than it already is. It’s easy for people in developed countries to feel guilty about the privileges they have with respect to people in developing countries. Everlasting youth would be quite something to feel guilty about if not everyone had it. Not developing rejuvenation might thus prevent first-world people from having yet another thing to feel guilty about, but that’s all it would do; it would not help third-world people in any way.

Let’s assume that we found out that rejuvenation would be so expensive that only very rich people could afford it, and, for this reason, we decided not to develop it at all. How would this affect the poor? We didn’t develop rejuvenation, so nobody got it, including the poor. If we had developed rejuvenation, the poor wouldn’t have gotten it anyway, because it would have been to expensive for them to afford. So either way, nothing changed for the poor, and they certainly didn’t benefit from rejuvenation not existing.

What about the rich? If we didn’t develop rejuvenation for fear of increasing the gap between rich and poor, then the rich – like the poor – would keep getting sicker as they aged. Surely this didn’t make the gap larger, but it didn’t make it any narrower either. Not developing rejuvenation (or any other new technology, for that matter) doesn’t help the poor, and doesn’t close the rich-poor gap. If we think about it, we see that simply closing the gap isn’t enough. What really matters is how we close it. If developed countries gave up on all their comforts and wealth and became like the developing countries, then the gap would be closed, but no one would benefit from it. The only sensible way to close the rich-poor gap is making the poor better off, not the rich worse off.

Conclusion

So, no, not developing rejuvenation isn’t the way to go. Rejuvenation, like anything that can improve human life, needs to be developed. The concern that rejuvenation might become a privilege of the rich only is legitimate, but the way to avoid this scenario is not to give up on rejuvenation entirely but rather to work hard to ensure that it becomes as widespread and affordable as basic medicine.

Each and every one of us has the power to do something in this sense – be it by working on the necessary science, supporting it financially, lobbying to change relevant regulations, or even just spreading the word and let everyone know about this possibility. Our journey towards a future free from age-related diseases for everyone will be as short – or as long – as we will make it.

Literature

[1] Konagaya, S., Ando, T., Yamauchi, T., Suemori, H., & Iwata, H. (2015). Long-term maintenance of human induced pluripotent stem cells by automated cell culture system. Scientific reports, 5.

[2] Rafiq, Q. A., Twomey, K., Kulik, M., Leschke, C., O’Dea, J., Callens, S., … & Murphy, M. (2016). Developing an automated robotic factory for novel stem cell therapy production. Regenerative medicine, 11(4), 351-354.

[3] Chen, V. C., Ye, J., Shukla, P., Hua, G., Chen, D., Lin, Z., … & Hsu, D. (2015). Development of a scalable suspension culture for cardiac differentiation from human pluripotent stem cells. Stem cell research, 15(2), 365-375.

[4] Conway, M. K., Gerger, M. J., Balay, E. E., O’Connell, R., Hanson, S., Daily, N. J., & Wakatsuki, T. (2015). Scalable 96-well plate based iPSC culture and production using a robotic liquid handling system. Journal of visualized experiments: JoVE, (99).

[5] Granzin, M., Soltenborn, S., Müller, S., Kollet, J., Berg, M., Cerwenka, A., … & Huppert, V. (2015). Fully automated expansion and activation of clinical-grade natural killer cells for adoptive immunotherapy. Cytotherapy, 17(5), 621-632.

[6] Bulterijs, S., Hull, R. S., Björk, V. C., & Roy, A. G. (2015). It is time to classify biological aging as a disease. Frontiers in genetics, 6.

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

[8] Kennedy, B. K., Berger, S. L., Brunet, A., Campisi, J., Cuervo, A. M., Epel, E. S., … & Rando, T. A. (2014). Aging: a common driver of chronic diseases and a target for novel interventions. Cell, 159(4), 709.

[9] Scitovsky, A. A. (2005). “The High Cost of Dying”: What Do the Data Show?. Milbank Quarterly, 83(4), 825-841.

Date Posted: March 13, 2017

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Kelsey Moody – Developing a Therapy for Age Related Blindness

New medical technologies need bold researchers to make the leap from the laboratory table to hospitals and clinics, where they can improve or even save lives. Kelsey Moody, a 30-year-old scientist from Beekmantown, is one such researcher.

Kelsey is especially interested in the treatment of age-related diseases but is using a different approach. Currently, researching age-related diseases like cancer, Alzheimer’s, diabetes, Parkinson’s, and heart disease takes up huge amounts of funding; however, very few of these approaches aim to treat these pathologies at their root causes – the processes of aging – and this is why they are not successful.

His focus in the past few years has been developing an effective treatment for age-related macular degeneration (AMD), a leading cause of vision loss among people over 50.

The experimental treatment he’s working on, called LYSOCLEAR, is currently being tested for validity at Ichor Therapeutics, a startup Moody founded in 2013 when he was only a second-year medical student with a $540,000 grant received from the Life Extension Foundation. LYSOCLEAR is based on the LysoSENS approach advocated for by the SENS Research Foundation, where Moody worked as an academic coordinator first in 2008-2010 and as a research scientist in 2012.

Both age-related and juvenile-onset macular degeneration are believed to be caused by the accumulation of waste products in the retina cells of patients. This accumulation leads to deterioration of the retina itself and eventually to vision loss. Ichor’s treatment uses special enzymes to break down one of these waste products, which is called A2E. The hope is to prevent and maybe even reverse the disease.

Moody’s company has received both public and private funds for over 3.2 million dollars, and his efforts have been praised by many experts, including Cornell Medical College ophthalmologist Szilard Kiss, Syracuse University professor Robert Doyle, and SENS Research Foundation Chief Science Officer Aubrey de Grey.

Now that LYSOCLEAR’s first efficacy tests are complete, 15 additional million dollars will be needed to move to more thorough animal testing and finally to human clinical trials. If all goes well, this may happen within the next three years.

Kelsey is a long-time supporter of the SENS approach, an approach proposing to repair the damage that the aging processes do to help maintain health and delay age-related diseases. As he said to Fight Aging! during a recent interview, one of the main reasons he chose to focus on the treatment for age-related macular degeneration is that, in his opinion, it is the SENS therapy closest to clinical implementation.

If LYSOCLEAR turns out to be successful, it would go a long way towards further validating the whole paradigm. However, AMD is not the only focus of Ichor; the company also works on acute myeloid leukemia, a type of blood cancer with low survival chances.

In addition to his ongoing studies as a Ph.D. candidate in Biochemistry and Molecular Biology through the University of Miami, Moody received an MBA from Concordia University, Wisconsin in 2013 and completed two years of medical training at SUNY Upstate Medical University.

He was also Chief Technology Officer at ImmunePath, Inc. and is currently Adjunct Faculty at Onondaga Community College and a mentor for the 20 Under 20 program at the Thiel Foundation. Kelsey’s next goal after a treatment for AMD is to go back to stem cell research, perhaps ushering new SENS treatments to the clinic.

How did you learn about the SENS approach?

I first came across SENS during an online review on regenerative medicine, and this initiated my interest in the study of human aging. At the time, I had no formal training in science. However, Aubrey’s approach made sense to me at face value, so I purchased his book to study it further.

After completing the book, I felt that I did not have sufficient knowledge to know whether or not his ideas were worthy of serious pursuit, but I was intrigued. I added a major in biochemistry and reasoned to myself that I would commit to the study of aging until such a time as it was clear to me that such a pursuit was not feasible or a worthwhile use of my time and resources.

Now, a decade later, I have graduate-level training in research, business, and medicine. While the conversation has become much more sophisticated, the original plan holds true. I have not reached a point where I believe SENS is unworthy of serious study.

I have focused my company on translational research because I believe that this is the area where we can have the greatest impact and where the largest deficits exist among the various longevity organizations, both nonprofit and commercial.

How easy (or difficult) would it be to adapt LYSOCLEAR to target different types of waste products in lysosomes of different tissues?

The idea of LYSOCLEAR is based on enzyme replacement therapy, which has already been used extensively in a clinical setting for the treatment of lysosomal storage diseases. In principle, the concept of “upgrading lysosomes” can be extended to numerous diseases of aging. The challenge is almost always in identifying ways to efficiently and specifically target the payload to its destination.

This is somewhat easier when your target cells are well studied and express receptors known to facilitate efficient targeting, such as monocytes or (in our case) retinal pigmented epithelial cells. It is a harder technical problem for other tissue types. Broadly, though, I am optimistic that this approach can be repurposed for other diseases, either by our team or others.

What other age-related diseases could be prevented or cured by clearing the waste from lysosomes?

Atherosclerosis immediately comes to mind, and SENS Foundation has funded research to identify enzymes capable of degrading plaque components, such as 7-ketocholesterol. There is a growing body of research linking lysosomal dysfunction to a number of neurological diseases, but I am not up to date on that research, so I’ll refrain from speculating.

LYSOCLEAR may be the first SENS therapy to make it to the clinic. What do you think might be the next one?

There seems to be a lot of good work and focus on delivering senolytic drugs to the clinic. Depending on how you define “SENS therapy” (i.e. based on the SENS concept or spinning out of SENS Foundation directly) I would imagine the next therapy to be in this field.

Can you tell us more about your work on acute myeloid leukemia? Do you base your approach to this disease on the OncoSENS paradigm, or is it something different?

This is an entirely different project. Some years ago, a paper was published that stated rats who were fed a nano compound called buckminsterfullerene had a doubling of their lifespan as compared to controls. However, this initial work was not a lifespan study. It was a chronic toxicology study, and the rats just happened to be allowed to live out their lives. It was underpowered and not designed as a proper lifespan study.

Given the striking apparent effect, a number of donors and investors have expressed an interest in seeing more work done in this space. However, testing this and related compounds to make mice or rats live longer does not constitute a viable translational path. We have obtained data showing that buckminsterfullerenes could be effective for treating various types of cancer or perhaps for reducing the adverse side effects from chemotherapy and radiation therapy.

Our interest is to test buckminsterfullerenes for longevity properties, but we need a disease indication that is firmly grounded in reality (i.e. acute myeloid leukaemia) to accompany our moonshot (an anti-aging drug).

In the past few years, senescent cell clearance has been a hot topic in the field of geroprotection. Would you like to work on this type of treatment as well in the future?

There are other groups that appear to be well positioned to lead the charge with senescent cell clearance, so it is unclear to me what we might be able to contribute to this work. I suspect that our attention will likely be applied towards other areas once our LYSOCLEAR program is in the clinic.

What are the main obstacles you have met at the early stage of your project? How could the general public and active supporters eventually help aging researchers the most?

The recurring challenge I see in the aging space is that the overwhelming majority of “anti-aging” researchers have little to no formal scientific training or wet lab experience (and it shows), or they are basic scientists. Virtually none have translational experience – that is, experience moving benchtop discoveries into a path towards commercialization.

Conversely, the translational scientists I have interacted with over the years are almost transactional, and they seem to be lacking the creativity and imagination of how new technologies could be applied to solve complex medical problems. Most of the people with ideas cannot execute, and most of the people who can execute lack vision.

We try to address this issue as a company by having one foot firmly in the fringe and the other firmly in the mainstream. For example, about half of our staff are futurists with a passion for anti-aging and SENS, but we balance that with experienced pharmaceutical professionals who keep us grounded and focused on actionable discoveries and a legitimate translational strategy.

Likewise, all of our drug development programs include a far-reaching “moonshot” opportunity but also a highly conservative disease indication.

Do you have any closing thoughts for the readers?

In my mind, the most important thing the public and active supporters can do to help aging research is education. I have found that a lot of supporters really approach aging science as almost a religion. A new paper comes out showing compound X improves a few biomarkers in flatworms, and suddenly people start taking that supplement.

If we want aging science to be taken seriously and become adopted as a mainstream and legitimate discipline, we need to hold the field to higher standards. That begins with top supporters becoming the most educated and vocal critics. Our company has built a transparent and open research culture.

We pursue answers to questions; we do not care about who was right and who was wrong – and everything anyone claims is a lie until it works in our hands. The result of iterating projects through such a culture is that the projects that survive have a strong basis in reality and represent viable drug development programs that have a real opportunity to work in the clinic.

We need to demand that projects we support as an anti-aging community have actionable successes and clearly defined fail points. We also need to celebrate scientists who do a good job in failing projects inexpensively and thoroughly and who don’t get caught up in the hype of poorly designed studies and anecdotes.

Conclusion

We would like to thank Kelsey for taking the time to speak with us, and we wish his company success in developing LYSOCLEAR.

Date Posted: February 21, 2017

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The Record Lifespan of 122 Years Could Be Surpassed

Today, February 21, is the birthday of Jeanne Louise Calment – the oldest verified human being ever, who managed to live an amazing 122 years and 164 days!

Jeanne was an independent and positive person, and she managed to live all alone until age 110. After a fire in her apartment, she moved into a nursing home, but even there, she was still able to take care of herself. However, shortly before her 115th birthday, she fell down a stairway and never fully recovered her ability to walk.

Surprisingly, when Jeanne was 118 years old, cognitive tests revealed that she scored within the normal range and lacked signs of dementia. However, by that time she was physically frail and required a wheelchair.

There is no doubt that her record helped millions of people readjust their expectations of the maximum possible human lifespan. However, in the eyes of an ordinary person, living for that long in a state of age-related decline does not really sound like the life of their dreams.

Luckily, modern science is aiming for another goal: an extended period of health and youthful vitality, sometimes referred to as negligible senescence.

In multiple interventions in animals, it has been shown that by addressing the underlying processes of aging in young or middle-aged animals, we can help them maintain their health and activity; now, research efforts are focused on translating the same technologies into clinical practice for humans.

If, or rather when, that happens, chronological age will no longer be closely related with biological age; aged people will potentially remain strong, good-looking, and creative.

Is this a goal worth working for? We think so.

To better understand the concept, let’s take a look at this tab comparing the features of a naturally old person and a negligibly senescent person. Of course, this is just a speculation, but it is helpful to visualize the expected results of the rejuvenation biotechnologies that are currently being developed by the SENS Research Foundation and many other research organizations around the world.

*115 years is considered by some scientists to be the maximum natural human lifespan without the application of rejuvenation biotechnologies.

As you can see, negligibly senescent people people should look, feel, and be as capable as modern young and middle-aged people. However, there is also a difference: the experience collected during 80+ years of life could potentially make people more skilled, more rational, more socially responsible, and probably more kind – just as we witness these qualities in our older colleagues and our grand parents right now. Living longer can make us more human, argues Didier Coeurnelle, one of the most active European advocates of healthy life extension, in his recent TEDx talk.

When we celebrate Jeanne Calment’s birthday, let’s remember that the most human thing to do is not just to remember the record but to try hard to surpass it. Jeanne died in 1997, so she could not benefit from the advances in aging research that are available to us now.

Knowledge about healthy lifestyle choices (healthy diet, physical activity, healthy sleep, no smoking, low alcohol consumption, active social interaction) is accessible to everyone and remains the foundation of healthy longevity. We are also getting more and more data on which drugs and supplements can promote health and help us postpone age-related decline.

More powerful therapies are on the way, but, on average, it takes up to 17 years for new drugs and therapies to be approved. For some of the problems caused by aging, such as amyloids and protein crosslinks, there are still no effective treatments, even for mice.

That is why, if we would like to bring the aging processes under substantial medical control more rapidly, we should all consider giving a hand to the researchers. Crowdfunding for fundamental studies on aging, supporting more early-stage biotechnology startups developing preventive therapies, and advocating the need to switch to preventive medicine are the best ways to foster progress.

During the last years of her life, Jeanne used to say, “I have only one wrinkle… and I’m sitting on it.” Doesn’t it look like good health and youth is the real dream of a supercentenarian?

Date Posted: February 15, 2017

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Age-Related Blindness Drug Moving to the Clinic

The development pipeline for new drugs and therapies is a long one, and, on average, it can take up to 17 years to research, test, and bring a new drug to market [1]. The reasons for this are myriad and complex, and they include the demanding test phases required for safety and efficacy, preclinical tests, regulatory paperwork, and the need to raise funding to pay for the increasingly higher costs of R&D that accompany such projects.

In 2016, a new study of R&D costs estimated the cost of developing a new drug to be $2.558 billion. This figure per approved compound is based on estimated average out-of-pocket costs of $1.395 billion and time costs (expected returns that investors forego while a drug is in development) of $1.163 billion [2]. In short, bringing a new treatment to market is hard; this is why the news about a unique treatment for treating age-related macular degeneration heading to clinical trials is so exciting.

Ichor Therapeutics, a biotechnology company focused on developing drugs for age-related diseases, has just announced its first major series A investment round to bring its LYSOCLEAR product for age-related macular degeneration and Stargardt’s macular degeneration to Phase I clinical trials. This product would be the first clinical candidate based on the SENS paradigm pioneered by biomedical gerontologist Dr. Aubrey de Grey.

About age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of vision loss among people over the age of 50. Over 20 million Americans and 450 million people globally [3] are affected by this condition. 85% of all cases arise from the progressive loss of photoreceptors in the macula – a part of the eye responsible for central vision. The underlying pathology of AMD is thought to be caused by the death of retinal pigmented epithelial (RPE) cells, which photoreceptors in the macula rely upon to feed and survive.

With time, different byproducts are formed that accumulate in the lysosomes of RPE cells (lysosomes are cellular structures responsible for recycling waste) and interfere with their function. One of these aggregates is A2E, a toxic compound that may play a causative role in AMD and SMD.

LYSOCLEAR is an enzyme product that can enter the lysosomes of RPE cells where A2E accumulates and destroy it. Ongoing studies suggest that LYSOCLEAR is safe and effective at targeting A2E, eliminating up to 10% with each dose. Clinical trials will test this new therapy in humans to identify the optimal dose and application regimen.

Ichor is a shining example of our mission to kick-start the rejuvenation biotechnology industry with a project that we initiated with early donor support. Led by one of our most dynamic and accomplished alumni, Kelsey Moody, Ichor is forging ahead faster than we could have dreamed. – Aubrey de Grey

For an outside observer, it may seem that such breakthroughs just happen in an instant. The truth is that there are decades of constant effort behind each event of this scale. Let’s take a short glance at the past.

A bit of background

Dr. Aubrey de Grey proposed a repair approach to treating the diseases of aging back in the 2000s. Methuselah Foundation first attempted to support scientific research on aging in 2003. In its first article, Aubrey introduced his approach to academia, naming it SENS, which stands for Strategies for Engineered Negligible Senescence [4]. SENS divides aging into seven categories of damage (including toxic protein aggregation in lysosomes) and proposes repair therapies for each of them.

By addressing the aging processes one by one, medicine could prevent and treat age-related diseases to hopefully keep people healthy and independent as they grow older. Aubrey has received more than his fair share of criticism during this time; however, he was not one to give in easily. In 2009, he co-founded the SENS Research Foundation to develop the therapies and approaches he proposed. Since then, SRF has been working tirelessly to bring the cutting edge technologies it proposes into being and ultimately to market.

Successful crowdfunding activities allowed SENS to support fundamental research in many directions. Late last year, we saw the first proof of concept for its MitoSENS program aimed at repairing mitochondrial damage with a publication demonstrating that this particular SENS technology could be practical.

The OncoSENS fundraiser in 2016 helped to launch a high-throughput screening of a library of diverse drugs to find treatments for cancers that rely on alternative lengthening of telomeres. These ALT cancers correspond to 15% of all cancers, and there is no cure for them at the moment.

Fundamental research like that promoted by SRF does not directly lead to drug development, but it enriches our knowledge base, helping to find promising candidate drugs and therapies. The next logical step is translation, in which biotech startups bring candidate therapies to clinical trials.

Luckily, as at this stage the end-product can start bringing profit, it is much easier to attract investment for its further development. Last year, biotech company Unity Biotechnology announced $116 million in Series B financing to bring senescent cell clearing therapies into human clinical trials in the next year or so. The SENS Research Foundation supported some of the key researchers behind Unity for many years, as senescent cell clearance is again another SENS therapy and part of its ApoptoSENS approach.

In 2014, Ichor Therapeutics completed a material and technology transfer agreement for rights to the concepts and research pioneered by SENS Research Foundation. Now, Ichor has opened a Series A funding round to support preclinical Investigational New Drug (IND) enabling studies and phase I human clinical trials for AMD and SMD.

The company has established a partnership with Syracuse University and obtained dedicated seed funding for the program from Kizoo Technology Ventures, SENS Research Foundation, FightAging.org, CenterState CEO, and several private investors to support its present work on LYSOCLEAR.

So, things are moving forward, and we are now seeing the first SENS therapies proposed back in the 2000s moving into clinical trials. The timeframe is about right, given the current pace of research. Hopefully, we will see Ichor succeed, as millions of people around the world will be protected against age-related vision impairment caused by AMD and SMD and will be able to live their lives to the fullest for longer. Source: LYSOCLEAR Press Release

Literature

[1] Morris, Z. S., Wooding, S., & Grant, J. (2011). The answer is 17 years, what is the question: understanding time lags in translational research. Journal of the Royal Society of Medicine, 104(12), 510-520. [2] DiMasi, J. A., Grabowski, H. G., & Hansen, R. W. (2016). Innovation in the pharmaceutical industry: new estimates of R&D costs. Journal of health economics, 47, 20-33. [3] Mariotti, S. P. Global data on visual impairment 2010. Geneva: World Health Organization; 2012. WHO/NMH/PBD/12.01. [4] De Grey, A. D. N. J. (2005). A strategy for postponing aging indefinitely. Studies in health technology and informatics, 118, 209.

Date Posted: February 13, 2017

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Four Main Economic Implications of an Aging Population

Most of the generation born in the 1980s enjoyed watching the science-fiction adventure comedy film “Back to the Future”. The plot is built around the idea that, by using a time machine, one can go back in time to fix things that have gone wrong in order to help the present get back to normal or to improve the future.

Sadly, humanity does not have such a machine, but we have something better. Expert, evidence-based forecasts can help us understand what our future is likely to be, hence enabling us to undertake measures to make it as bright as possible.

With the global population aging rapidly, there are four main economic implications that we should take into account for reasonable decision-making: a shrinking workforce, decreasing social security contributions, increasing healthcare expenditures, and an insufficient caretaker workforce.

As Arthur Guarino, an assistant professor in the Finance and Economics Department at Rutgers University Business School, explains in his recent article for Global Risks Insights:

One key economic implication of an aging population is the strain on social insurance programs and pension systems. With a large increase in an aging population, many nations must raise their budget allocations for social security. For example, India’s social security system presently covers only 10 percent of its working-age populace, but its system is operating at a deficit with more funds exiting than entering. In the United States, projections state that the level of social security contributions will start to fall short of legislated benefits this year. In other words, the amount of money coming into social security will lessen due to fewer contributions from workers and more funds going to an aging retired population. In Europe, in order to fund their social security system, 24 nations have payroll tax rates equaling or exceeding 20 percent of wages. The situation is also precarious for pensions. As the global population for elderly and retired workers increases, pensions must provide more income to these recipients so that they can enjoy at least a reasonable standard of living […] […] Another key economic implication of an aging population is the increase in health care costs. As the population ages, health generally declines with more medical attention required such as doctor visits, surgery, physical therapy, hospital stays, and prescription medicine… …For example, in the United States, it is projected that public health expenditures will rise from 6.7 percent of GDP in 2010 to 14.9 percent in the year 2050. This increase in health care costs will mean that nations must put more funds and human resources into providing health care while also attending to the needs of other segments of their people. With an increasing aged population, there will also be shortages of skilled labor trained to care for aged patients. It is projected that the registered nurse workforce in the United States will see a decline of nearly 20 percent by 2020 which is below projected requirements […] […] Nations, such as China and Mexico, are expected to witness declines in their workforce from the year 2030 to 2050. Other large economies such as Japan are projected to see a 19 percent decrease in their worker population within the next 25 years followed by a 24 percent decrease over the next 20 years. Europe is also expected to see declining numbers in its workforce which will impact their chance to have a growing, competitive economy. This decline in the global workforce will lead to an increase in the age dependency ratio which is the ratio of working-age to old-age individuals. Globally, the dependency ratio in 1970 was 10 workers for each individual over age 64, but the expected ratio in 2050 is four workers for each person over 64.

Sadly, the main call for change is focused on the increase in fertility. China, Japan, Vietnam, Italy, Spain, and other countries facing a rapidly aging population are undertaking measures to encourage reproduction.

This alone, however, cannot lead to rapid improvements, because many developed countries need additional workers now and not 20 years from now; similarly, the number of people of reproductive age is small and the absolute number of births may not be high enough.

That is why it is crucial for the global community to see rejuvenation biotechnologies as an important part of the solution. If therapies to slow down the aging processes are applied to middle-aged people, this could postpone the overall health decline in the working generation and help people remain on the labor market for longer. This, in turn, would help maintain sustainable economic growth.

Date Posted: February 9, 2017

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From mechanic to medicine: How one man became a scientist

Today, we will cover a story about how a member of our community, Mike Daniels, car mechanic turned cancer researcher, was inspired by the work of the SENS Research Foundation to address age-related diseases. What follows is an emotional, gritty but honest life story of someone who took action and is now doing amazing things in his life for science.

Firstly, can you tell us a little about yourself?

Certainly, I am a first year Biostatistics PhD student at the University of Colorado. I met my wife in 2003 from an online dating website just two days after being mobilized for the Iraq war. As a 42-year old father of two daughters, I stay in touch with my parents whom still live in Appalachia where I was raised. I am unsure if I am a contradiction or a bridge between two worlds. Listening to J. D. Vance’s Hillbilly Elegy reminds me of my roots growing up along US 23 in Eastern Kentucky.

In contrast, just yesterday, I presented a journal review to a classroom filled with intellectuals such as doctors, biologists and mathematicians. As a liberal, atheist scientist with religious, conservative family and friends, I understand why voters turned out for president-elect Donald Trump and why protesters are taking to the streets. Carl Sagan said we are nothing but a pale blue dot, a mote of dust in a sunbeam, just to put everything into perspective.

So who am I? I’m the guy who fixed your air conditioner, roofed your house, changed the spark plugs in your car’s engine, worked the production line in a food factory, defended your country during war, waited your table at your favorite restaurant and even washed your dishes after you were done. Now, I want to join the united front to end the most widespread cause of human suffering – aging.

When did you first hear about SENS and what was it that interested you about the concept?

It was a very serendipitous moment that inspired me to read Aubrey de Grey’s book Ending Aging in 2008. I was living in Louisville, Kentucky and spent my free time from working at a White Castle frozen hamburger factory hanging out in a local coffee shop called Heine Brother’s Coffee. Adjacent to that coffee shop was Carmichael’s, a local, independent bookstore. Sitting in a booth in the coffee shop one morning, I was feeling down due to the tough finances of working a blue collar job, lack of sleep from caring for two babies and the misery of war that dominated the news.

Looking down a hallway into the bookstore, a beam of sunlight shone down during a cloudbreak. I left my seat to feel that light on my face to lift my spirits. I must have basked there for nearly a minute. Afterwards, I went straight to my favorite section, Science & Math. And what I found was not just a book, but hope. While Barack Obama was telling us all about hope and change, I was discovering it for myself. Ending Aging spoke to me. Dr. de Grey told us not to accept humanity as the limits of our DNA.

Challenge the status quo and possibly discover how great we may become. Every generation believes that they can do better than their parent’s generation. Until one day that generation wanes into the symptoms of aging. Great men and women lose their dignity because a care worker or family member has to perform what once were remedial tasks for them. Even as their body and mind deteriorates, the younger generation works diligently to absorb their wisdom and love.

This touched me deeply because I loved my parents, grandparents, aunts, uncles, cousins, and other family members and friends. For religious people, you can squelch some of the pain from losing someone to aging with the thought of seeing them again in heaven or some other afterlife concept. As an atheist, I didn’t have that option. The seed of Transhumanism was planted within me and Aubrey de Grey was to blame.

The indecencies attached to the aged bodies of our loved ones wasn’t what sold me on SENS. Dr. de Grey’s analogy of maintaining an antique car caught my attention early in the reading of his book. This was a direct appeal to my inner mechanic. I read during my 30-minute lunch breaks at the White Castle hamburger factory. Separating six burgers into three sets of two on a transfer belt and sliding them into a moving slot to be wrapped in cellophane at a rate of one pair per second, I would let my mind wander into another world.

What are the seven categories of damage that would need to be reversed? Is this list all encompassing? Doing repairs may be easier than changing metabolic pathways, but would it even be possible. What would a society be like if age-related illnesses were eliminated? Aubrey addressed each of these issues and the scientific community slowly started to accept his ideas when they couldn’t disprove them. I was onboard and wanted to be a part of the next step in human improvement.

What did it inspire you to do?

There was this moment where I decided to stop spoon feeding my wife the ideas of SENS and unleashed all my thoughts on her at once. It took place during a long hike where unconsciously I knew she couldn’t escape. She remained quiet and a little scared for hours while I spoke of cellular biology, the ills of aging and my plans to become a doctor or researcher. She held two Master’s degrees. I, on the other hand, was busy retraining National Guardsmen who were heading to Iraq and worked various positions in a frozen food factory along with several low paying manual labor jobs.

I wasn’t naïve to the difficulties of academic life. I did well academically in high school graduating with a 4.0 and winning 1st place in a district academic meet in mathematics. I attended Virginia Tech to become a chemical engineer but wasted my years not focusing on studies. Instead, I focused on failed relationships, peer approval through excessive partying and losing my religion. The final straw came when I had a mental breakdown from financial hardship.

My friend took me to an emergency room because she feared I was going to commit suicide. I hadn’t even told her the moments where I entertained the idea. Living in a rundown apartment without money or food, I took my last breath and submerged myself into the bathwater locking my legs in a manner that would make it difficult to escape. I looked up at the surface of the water and listened for God to speak to me. I heard nothing.

This shocked me because I was committed to the task at hand. In disbelief, I untangled my legs and slowly rose out of the water like an atheist baptism. My perspective of the world was wrong. I was living a lie. I packed up my car with some essentials, left most of my possessions behind and headed back to Eastern Kentucky. While driving home, I had convinced myself that I would never attend college again and I would find a new path to happiness.

I spent the next decade struggling to make ends meet. Various levels of depression oversaw my behaviors. I worked menial jobs, engaged in fist fights, became homeless for a couple of short stints and embraced risk-taking as a way to feel something inside over the numbness of a failed life. By the time I met my wife I was stabilized. I couldn’t tell her all the things I had seen and done out of fear she might wise up and leave this Hillbilly alone. So when I proposed the idea of me becoming a researcher, she was worried that our stable life would enter the chaos of my former life.

It became apparent that working 60+ hours a week at a factory and having two kids under the age of three would not be an ideal time to go back to school. Hence, we waited. I obtained a horizontal promotion as a service technician for the restaurant division. I loved this job. I learned how to braze copper for air conditioning, worked concrete, operated scissor lifts to change out parking light ballasts and repaired deep fryers, grills and milkshake machines. I still read cellular biology books in my spare time and googled Aubrey de Grey more than once a week to see his progress. Then, an opportunity presented itself to me.

My neighbor worked for Kentucky Organ Donor Affiliates (KODA) as a Donor Center Coordinator. He found it interesting that this mechanic neighbor of his was reading biology textbooks when he wasn’t being called out in the middle of the night to fix a freezer. He asked me if I would be interested in a career in the medical field and said he could get me an interview but that was it.

After waiting for three and half years, I had to decide if I should risk it all to pursue my dream. Soon I would not be the only one taking a chance. I had to submit a resume before my interview. There was nothing in my past that would qualify me for this job. I prepared a bare bones resume. My new boss confronted me on the simplicity of my resume. I told him that there was nothing on paper that would qualify me for this job.

He rebutted, “So, why should I hire you?” I explained to him that my qualifications were in my mind and my heart.

He quizzed me on biology, medicine and interpersonal skills. I compared the cardiovascular system to an air conditioner. The heart is the pump. You have a high and low pressure side. The capillaries were like evaporators but instead of absorbing heat they were delivering oxygen and nutrients. He hired me and said they could teach me what I didn’t know. I accepted the lower paying job which worked from 7 PM to 7 AM three days a week and started attending the University of Louisville during the day shortly thereafter.

Wow, so you changed your career completely, how hard was that to do and what were some of the challenges you encountered?

Well, your intuition is correct about the difficulties of switching careers. The transition was tough because I chose to work both jobs for a couple of months to ensure myself that I could do the job. I used all my vacation from White Castle to train during the day at KODA. Once “vacation” ended, I trained on night shift and worked my maintenance job during the day. Also, I was on-call at night every other week for maintenance emergencies.

One night after working non-stop for three days, I couldn’t fall asleep because my heart was pounding and my face and extremities went numb. Like many people, I had mistaken my first anxiety attack as a cardiac event. My wife drove me to the ER where the doctor said that my EKG and blood work were perfect. He asked, “Are you experiencing any stressful events in your life?” One aspect of my new job “The Approach” took place the night before my anxiety attack.

As a Donor Center Coordinator for KODA, I received call-in death reports from nurses in one of our associated Kentucky, Indiana and West Virginia hospitals. After screening the medical history of the patient, I had to determine eligibility for tissue and eye donation. Potential candidates for donations required consent from the next of kin regardless of registry status. It was a nerve-wrecking event to ask the legal next of kin for consent just minutes after their loved one’s death.

If consent was obtained, then I recorded a 20 to 30-minute medical-social questionnaire, which included invasive questions dealing with health, sex, drug use and jail time. I spent the next five years failing to remedy my anxiety by trying eight different anti-depressants. Yet, the experience of making a difference in people’s lives and working with some of the best coworkers I’ve ever had made it all worth it. With great support from family and friends, I finished two degrees, BS Pure Mathematics and MS Biostatistics.

So what are you doing right now as part of your studies?

Currently, I am focusing on my studies as a first year PhD student in Biostatistics in the beautiful state of Colorado. The teaching staff here is incredible. They are pushing me to be the best I can be while still providing me some space to allow my family and myself to adapt to our new environment. I am taking a course on genomics which has a strong emphasis on the technology of measuring gene expression and various sequencing platforms.

I just published my first paper in Breast Cancer Treatment and Research as a primary author, called “Clinical outcomes linked to expression of gene subsets for protein hormones and their cognate receptors from LCM-procured breast carcinoma cells”. This paper evolved from my Master’s thesis. I will be presenting my work at the San Antonio Breast Cancer Symposium in December. I was honored to be accepted for the 2nd time and a 3rd poster presentation.

Soon I will be collaborating on a methods based paper with my new colleagues at the University of Colorado Denver as part of my research assistantship.

What do you enjoy the most about your work?

I enjoy the science. As a statistician, I have the pleasure of testing real hypotheses. Why is that a pleasure? Because you can hypothesize as many good questions as you want, but unless you have the skill set to quantify those questions, you can’t answer it with any appropriate level of certainty. In addition, it can be challenging. The greatest reward comes from overcoming the greatest feats. With the incredible volumes of omics data challenging scientists, there emerges possibilities for novel discoveries.

Which of the seven areas of SENS interests you the most and why?

I would have to say OncoSENS. My research has been in breast cancer and I’m learning more about epimutations in my genomics class. Also, most of us know someone close that is fighting cancer, survived it or succumbed to it. My mother-in-law starts chemo and radiation this week in her fight against breast cancer. I could overwhelm the rest of this interview with stories of triumph and loss from the disease. I want humanity to learn how to control damage in all the seven areas, but this one I take personally.

What do you think about the shift in aging research towards crowdfunding, for example, the recent OncoSENS and MitoSENS projects on Lifespan.io?

I was delighted to see the progress that the SENS Research Foundation has made in this area. I believe it connects people more intimately with the benchtop research, the scientists and the research community. It can feel good to donate to charity or a cause, but you don’t really know how your donation is being implemented other than generalities. Crowdfunding makes you feel like your Mark Cuban in the Shark Tank trying to discriminate not only what product (research) might work but what product you want to be apart of.

What are your future plans career wise?

Get my doctorate! As my granny always said, “Don’t count your chickens before they hatch.” Given that statement of humility, I would like to work on a research team in a biotech company. I am open to academic research and wouldn’t discount any opportunity. My desire is to spend my days working with innovative people to solve the mysteries of controlling aging. I don’t care what platform provides that for me.

Do you have a take home message for those reading who might want to help but think they have nothing to contribute?

Yes, first I want to thank LEAF for giving me this opportunity to speak to the community. My only purpose here is to inspire someone else to find their way to make a difference. When I started I didn’t know it was going to be entering academia. I certainly didn’t know it would be learning biostatistics, a field unbeknownst to me until I neared the completion of my BS Mathematics degree. Be patient, but also be vigilant to find that connection to the next chapter in your life. I described my history in a very exposing, intimate manner because I couldn’t convey my honesty without those details. It wasn’t easy. I had to fight for it. I had to fail more times than succeed. You may not even know what special skills you possess and can offer until you try something.

Controlling the scourge of aging probably needs funding more than another person with a science degree. If you have the money to give, then let my story be a microcosm of the passion of the researchers working at SENS and its affiliates. If I weren’t a poor 42-year old college student, then I would entrust my money with someone like me. Someone that doesn’t care about status or personal wealth. Someone that feels it is their purpose in life to end the largest contributor to human suffering.

I have always believed Dr. Aubrey de Grey is that person. I also believe that most of the people working for him aren’t his employees. They are his compadres in a war to defeat an enemy that has dominated us since life began. We are the soldiers of compassion. Now, you have to choose your weapon. I’m sure there are some of us that can’t financially contribute, but you can advocate for the cause. I’m doing just that by telling you about my journey.

Feel free to share my story with someone you think it may inspire. Let’s shift the paradigm away from the normality of age-related death.

Conclusion

We would like to thank Mike for taking the time to share his life with us and for his honest and inspiring story. Advocacy is all about the willingness to take action and do something about a situation; we hope Mike’s story has inspired some of you today.

According to the U.S. Department of Labor, women make approximately 80% of the health care decisions for their families.

Date Posted: February 8, 2017

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Why Women Can Benefit The Most From Rejuvenation Tech

The world is currently experiencing a period of rapid population aging, with estimates stating that by 2050, about 22% of the global population will be aged 60 years or older; by the end of this century, that percentage might be potentially as high as 33%. This trend is so pronounced worldwide and so impactful that it is called the “silver tsunami”. Some countries are experiencing even faster population aging, such as Japan, where the share of people aged 65+ has already reached 26.3% and is estimated to be close to 40% by 2050 [1].

The morbidity structure of the population is changing accordingly: chronic age-related diseases have become the leading causes of disability and death in developed countries, and developing countries are quickly catching up.

Fig 1. The 10 leading causes of death in the world 2012. Top 10 causes of death in high income countries 2012. Source: WHO Media Centre.

Health care expenditures increase, and a shrinking workforce provides fewer resources to support the elderly. The old age dependency ratio (number of people aged 65+ by 100 people of working age) is also increasing worldwide. For instance, in the United States, the old-age dependency ratio, which was 22.3% in 2015, is estimated to increase to 36.9% in 2050 and could reach 47.9% by 2100 [1]. Currently, each American retiree is supported by 4 other people; by 2100, there will only be 2 helpers providing for their needs.

Recent studies in the EU (a region experiencing very fast population aging) show that higher old-age dependency ratio is related to lower income per capita growth over the last two decades. The researchers assume that there are potential negative effects of population aging on the future economic growth of Europe [2] – which may be the same for all other countries with a similar demographic profile.

Even though increasing life expectancy is certainly a great achievement of humanity, its consequences, such as a proportionally reduced workforce and the increasing morbidity of age-related diseases, create a number of risks for the economy. We cannot ignore this trend, and we must undertake a number of measures to ensure sustainable development of the global society in the medium to long term.

But who is going to deal with the increasing needs for caregiving?

According to the U.S. Department of Labor, women make approximately 80% of the health care decisions for their families, and they are also more likely than men to be caregivers to family members [3-5]. An American Academy of Family Physicians (AAFP) national survey (2008) has found that around 90% were responsible for health care decision-making for themselves and/or family members [6]. Women are more likely than men to play a role of primary family caregiver. For older adults, about two-thirds of caregivers are women [7].

Stakeholders in the field of elderly caregiving in the United States also report a deficiency of elderly care specialists and facilities, which is going to become worse in the future as the population ages and the workforce diminishes. Therefore, it is very likely that most of the burden related to nursing the disabled elderly will be placed increasingly on the shoulders of women, in both paid and unpaid (family) caregiving.

We can see it happening in modern Japan. The current old-age dependency ratio in this country (number of old people by 100 workers) is the highest at 43.3 and is estimated to reach 70.9 by 2050, which means that four workers will need to support three elderly people [1].

In a recent study, it was shown that women traditionally play the main role in caregiving in Japan, making nearly 80% of all caregivers. As the burden of caregiving has been increasing due to population aging, the government introduced a program of long-term care insurance (LTCI) to provide formal care with a 10% co-payment, based solely on a functional assessment of the recipient. As a result, the share of traditional female caregivers decreased from 78.2% to 68.6%, while male caregivers increased their participation. However, this also created higher risks of maltreatment for care recipients (because of the lack of skills for caregiving in men) [8].

So, if we use Japan as a prototype of what will happen to caregiving in developed countries, we can expect, as a result of the introduction of governmental support programs, that the amount of male caregivers will increase but the female caregiver group will still carry most of the burden on their shoulders.

That is not all. One of the solutions for population aging that is being actively promoted by different stakeholders is the increase of the birth rate; countries such as China, Japan, Vietnam, Italy, Spain, and others facing fast population aging are undertaking measures to encourage reproduction. The goal of these efforts is to bring balance in regards to population age, as more births will mean more young people who can enter the workforce.

The problem here is that the generation encouraged to procreate is also the same generation needed to increase their support for the elderly. As both children and elderly require care, based on the above statistics, this stands to place a potentially intractable burden on women in the years to come. It might indeed become much harder to live your life the way you want in 2050 if you are a woman.

Luckily, there is a solution; rather, there might be a solution, if women will help to create it. This solution is to increase support for research on aging and longevity. By helping the scientists developing effective treatments to slow down, arrest, and eventually reverse age-related damage, we can help prevent chronic age-related diseases.

The burden of cancer, cardiovascular diseases, osteoarthritis, hearing and vision loss cause a great deal of suffering to the elderly and are often the reason why people become disabled and dependent on their families. If such technologies are available to most of the population in middle age, it could help extend the period of peak health, enabling the elderly to avoid disability and to be independent and productive for longer periods of time.

Science is increasingly showing that the processes of aging are manageable, but to cope with the pace of the “silver tsunami”, we need to increase our support for research on aging now.

For women, this is a win-win investment, whether they are taking part in crowdfunding for aging research or joining rejuvenation biotechnology startups as business partners. If the various aging processes can be brought under medical control, women could be released from an additional burden of care of their shoulders in the middle-to-long term.

However, most importantly, by using these “health maintenance” technologies themselves, women could remain healthy and youthful for longer. After all, when most of us look in the mirror, we would prefer to see shining soft skin, youthful fitness, and the smile of a woman enjoying her life to the fullest at any age!

Literature

[1] United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, Volume II: Demographic Profiles (ST/ESA/SER.A/380). [2] Cuaresma, J. C., Loichinger, E., & Vincelette, G. A. (2016). Aging and income convergence in Europe: A survey of the literature and insights from a demographic projection exercise. Economic Systems, 40(1), 4-17. [3] U.S. Department of Labor. General facts on women and job based health. Washington, DC: U.S. Department of Labor, 2005. Available at: www.dol.gov/ebsa/newsroom/fshlth5.html. [4] Zimmerman MK, Hill SA. Health care as a gendered system. In: Saltzman-Chafetz J, ed. Handbook of the sociology of gender. New York, NY: Plenum Publishers, 1999: 483–518. [5] Grant KR, Amaratunga C, Armstrong P, et al. eds. Caring for/caring about: women, homecare, and unpaid caregiving. Aurora, Canada: Garamond Press, Ltd. 2004. [6] American Academy of Family Physicians (AAFP). Fixing health care: what women want. Leawood, KS: AAFP, 2008. Available at: https://www.aafp.org/media-center/kits/women.html. [7] Matoff-Stepp, S., Applebaum, B., Pooler, J., & Kavanagh, E. (2014). Women as health care decision-makers: Implications for health care coverage in the United States. Journal of health care for the poor and underserved, 25(4), 1507-1513. Available at: https://muse.jhu.edu/article/561554 [8] Tokunaga, M., Hashimoto, H., & Tamiya, N. (2015). A gap in formal long-term care use related to characteristics of caregivers and households, under the public universal system in Japan: 2001–2010. Health Policy, 119(6), 840-849.

Date Posted: February 3, 2017

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

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

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

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

The search for the secret sauce

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

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

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

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

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

Conclusion

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

Literature

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

Date Posted: January 20, 2017

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

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

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

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

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

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

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

Here is some relevant data from a recent study.

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

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

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

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

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

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

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

Conclusion

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

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

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

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

Date Posted: January 18, 2017

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

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

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

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

We might be able to filter aged blood

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

In The Guardian, Irina Conboy said:

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

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

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

Conclusion

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

Literature

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

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

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

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

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

Date Posted: January 16, 2017

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

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

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

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

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

Conclusion

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

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

Date Posted: January 14, 2017

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Dr. Aubrey de Grey – Reimagine Aging

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

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

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

No longer a taboo

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

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

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

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

The tide is turning

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

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

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

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

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

Conclusion

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

Date Posted: January 13, 2017

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New Therapy Could Make Chemotherapy Safer

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

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

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

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

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

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

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

Conclusion

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

Literature

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

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

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

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

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

Date Posted: January 10, 2017

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Synthetic biology could combat the aging process

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

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

Are you a for-profit company?

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

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

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

Is it safe to remove senescent cells?

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

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

Can your technology be used to treat other SENS damages?

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

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

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

Are senescent macrophages the problem?

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

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

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

When will we see results from your research?

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

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

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

Date Posted: December 10, 2016

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Promoting Your Right to Health on Human Rights Day

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

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

Article 2

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

Article 25

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

Article 27

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

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

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

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

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

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

Article 1

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

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

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

The right to health includes both freedoms and entitlements.

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

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

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

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

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

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

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

non-discrimination;

physical accessibility;

economical accessibility (affordability);

information accessibility.

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

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

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

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

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

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

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

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

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