The National Geographic's Breakthrough on Aging Research

The National Geographic has been fairly heavily engaged in promoting Breakthrough, a new popular science and technology show that edges its way around the outskirts of topics such as artificial general intelligence, transhumanism, and, of course, the medical control of aging, which in time will lead to extension of healthy life spans and elimination of age-related disease. Judging from what is out so far, this largely has the air of presenting a very watered-down, safe, unambitious vision of these goals to the public at large, while at the same time painting that as edgy and radical. So both condescending and missing the point at one and the same time. Still, they're sinking a fair amount of time and effort into this judging from the panoply of surrounding articles and the high-tech series website with its 3-D vision sphere effect. Also, albeit buried several layers deep in that set of marginally interactive spheres, you'll find video commentary from some of the folk in our community on the topic of radical life extension through medical science: Aubrey de Grey, Jason Silva, Sonia Arrison, Maria Konovalenko, and so forth.

Apart from that, most of what is on offer is focused on research efforts with marginal goals, such as the metformin trial that aims to be one small step towards very slightly slowing human aging, and researchers who believe that there is little more that can be done than this. For those who reject the SENS view of rejuvenation through targeted damage repair, or similar visions based on the Hallmarks of Aging viewpoint, research plans that could lead to radical life extension within decades if fully funded, there is little to see but a long, very expensive process of cataloging all of cellular metabolism and all of its age-related dysfunctions, and along the way using the traditional process of drug discovery to try to eke out very tiny beneficial alterations to the way in which aging occurs. This is a disappointing vision for anyone to be stuck embracing in a time of radical and rapid progress in biotechnology.

What Do Centenarians Know That the Rest of Us Don't?

Only about 5 people out of 1,000 live longer than a century. For the most part, these people get the same illnesses as everyone else - they just get ill a few decades later. Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York, is trying to understand why. He's been studying large numbers of centenarians who share similar genetics. Barzilai is conducting a major study on the diabetes drug metformin, which he has shown can delay the diseases of aging in animals.

"You have to be careful. Is metformin going to be good only? We hope. For 60 years, millions of [people have used it] and nothing bad has happened. But we'll see. Metformin is the way to pave the road. Once the pharmaceuticals jump into this field, we will get better drugs. That's why we think the next decade is really exciting. The fountain of youth is not what we're doing, but this is the first time that we understand enough about the biology and mechanisms [of aging] so we can really think of drugs that can help us."

The Secrets to Unlocking a Longer Life

Aging might not be such a crisis if people not only lived longer, but also stayed healthier and were able to continue to lead productive lives. That's why researchers are working to solve some of the mysteries of aging, and to figure out ways to counteract its effects. And while they haven't yet found a way to slow the aging process, in recent years they've made promising progress.

In recent years, scientists have discovered that longevity apparently has less to do with lifestyle than genes. A study published in 2011 found that those who made it to 95 or older were no more virtuous than the rest of us when it came to what they ate, how much they exercised, and whether they smoked or drank. Indeed, only 43 percent of male centenarians - those over 100 years old - reported engaging in regular exercise of moderate duration. 24 percent of long-lived men consumed alcohol on a daily basis, a slightly higher rate than the general population. "The study suggests that centenarians may possess additional longevity genes that help to buffer them against the harmful effects of an unhealthy lifestyle."

Of interest, there is a small section on senescent cell clearance stuck in the middle of that second article on longevity genes. This is the trouble with translating the essence of longevity science and its goals to the public at large. Those tasked with that effort are usually incapable of determining the difference between lines of research that absolutely cannot ever, even in principle, greatly extend healthy human life and produce rejuvenation, versus those that can. To them there is no difference between (a) hunting for genetic differences that raise the odds of living to be a centenarian from exceedingly low to slightly less exceedingly low, with an eye to giving other people that tiny extra boost to the odds, and (b) work on clearing senescent cells, which is one of the ways of repairing the fundamental causes of aging that could produce significant rejuvenation for any patient. It is all the same to the eyes of the layperson: here is a scientific program, here the scientist is working on something related to aging and longevity, check the box, move on.

I hear occasional complaints that I am partisan in my support of damage repair over, for example, drug discovery or epigenetic alteration as an approach to treating aging. That is because from where I stand the evidence strongly supports SENS-like programs aimed at damage repair as the best, indeed the only, way to achieve radical life extension soon enough to matter. There is a big, big difference in expected outcomes between the likes of carrying out trials for metformin and the likes of trying to make senescent cell clearance a viable treatment. It isn't all the same, and we are still stuck in the situation wherein most of the funding that comes into aging research is going to what is in effect purely investigative science, slightly dressed up with hopes of results because that works to raise funding, but like the metformin trial and the genetic studies in centenarians, these are efforts likely to produce nothing of use beyond more data on metabolism and aging. That's great in the pure science world, where no data goes to waste, but it won't get us to actual, working rejuvenation therapies. There are solid, sensible reasons for being an advocate of SENS and similar efforts, and front and center is the point that, given even a fraction of the funding that went to sirtuin development, SENS is much more likely to produce results that are big enough and happen soon enough to matter to you and I personally.

Comments

Hey there,

I have a hard time getting aroung the fact the certain things that exist right now already do what these two therapy intend to do. Metformin has natural analogues such as Berberine, cinnamon, lemon, bitter melon, mulberry, chromium picolinate, konjac viscous soluble fiber, resistant starch and vinegar acetic acid colon bacterial SCFA to name a few that improve insulin resistance, reduce HbA1c glycated hemoglobin and restore blood normoglycemia better than synthetic metformin biguanide can. Same goes for senescence cell clearance through the SIRT/Foxo/Daf-16 calorie restriction mimetic and senolytics such as Quercetin (found in grapes and wine) and Dasatinib. Activation of SIRT/Foxo/Daf during senescence cell clearance is a healthy effect (like CR) that will improve health/average lifespan and possibly maximal one too; the potency of this type damage repair will be as strong as Metformin is; which is to say, about a CR effect on lifespan.

Posted by: CANanonymity at November 28th, 2015 9:55 PM

@CANanonymity: It is a matter of degree. Calorie restriction doesn't do anywhere near as much to reduce senescent cell numbers as the senolytic drug combination, which in turn doesn't do anywhere near as much as would be possible via methods currently under development in the lab and startup companies. You can't just calorie restrict (or use the poor set of current alleged mimetics) and check the box saying you've taken sufficient action on senescent cells - we know the size of the resulting benefits in humans, and they don't significantly extend life, or significantly reduce senescent cell counts. We should be aiming at treatments that cut those counts by 90% or more in all tissues, not slightly adjust by a fraction of that amount.

Posted by: Reason at November 29th, 2015 7:46 AM

@Reason

Hi Reason, you are right, it's a degree issue now. I just hope we are capable of reaching that degree.
This study here tried in progeroid mouse and had success, albeit in a progeria model, the effects will be weaker in regular or longer than usual lifespan models (wild type, GHRKO mouse, Ames dwarf, Snell, Naked mole rat, ... possibly no longevity effect when all the way up to non-progeroid humans that are born with lucky centenarian genetic makeup and will reach 100-110 with little to no pathologies/morbidities; thus already fully optimized by nature in mother's womb). It makes me think of certain studies hitting a ceiling/limit that try to add CR + SIRT/Foxo/Daf in already long- lived mutant worms but fail to see any further lifespan extension effect; because the long-lived mutants already genetically optimized and profit from SIRT/Foxo/Daf pathways. Same thing goes on in centenarians capitalizing on Foxo3/Daf-16/SIRT. Let's hope ApoptoSENS can make that 90% reduction is senescent cells in all tissues and make mice (3 y) live the age of a naked mole rat (35 y).

1. http://www.nature.com/nature/journal/v479/n7372/full/nature10600.html
2. http://www.sens.org/research/research-blog/nothin-gonna-hold-me-back-clearance-senescent-cells-tissue-rejuvenation
3. http://www.pnas.org/content/106/8/2700.long
4. http://www.pnas.org/content/105/37/13987.full
5. http://www.ncbi.nlm.nih.gov/pubmed/20849522

Posted by: CANanonymity at November 29th, 2015 9:06 AM

I'm really curious to see what Oisin Biotechnolgy's approach turns out to be. Can they actually deliver it to all tissues using a liposome, or will it accumulate toxically in certain tissues (like RNAi did in the liver)?

Posted by: Jim at November 29th, 2015 5:17 PM

@Jim

I fear that too, liposome delivery is great but it seems that what is being delivered does not always reach intended target, thus the delivery doesn't always happen (kind of like lost in translation or sending a letter or parcel by post that never reaches the receiver and is lost forever 'out there' into the mail postage service oblivion). The reason seems to be about the hydrophilic non-lipid or hydrophobic lipid-like nature way the liposome is entwined with its hydrophobic content more than anything. PEG polymers (pegylation) and maleimide to liposome seem to be the problem. Liposome content delivery deposition accumulation is liposome size-dependent. Larger liposome = higher deposition cumul but at slower speed. Smaller liposome = lower deposition cumul but faster speed; so things even out, in the immediate smaller liposome is better by quidcker delivery, from small load. With more time, larger liposomes accumulate much more from larger load deposition. Larger liposomes would lead to more toxicity in the long term.

1. http://www.ncbi.nlm.nih.gov/pubmed/22381076
2. https://books.google.ca/books?isbn=0080536085
3. http://www.nature.com/scibx/journal/v7/n8/full/scibx.2014.237.html
4. http://www.ncbi.nlm.nih.gov/pubmed/17239468

Posted by: CANanonymity at November 29th, 2015 8:30 PM

But there is hope :

'' Moreover, because of reduced toxicity of liposomal drug [liposome encapsulation delivery seems to render toxic content non-toxic. This lipid bathing/engulfing delivery method abrogates toxicity; perhaps acting such as a buffer during unloading, just like a lubricant layer], higher doses could be administered, resulting in a significant reduction in the numbers of CFU
in the *liver*, speen and kidneys. ''

5. http://aac.asm.org/content/40/8/1893.abstract

Posted by: CANanonymity at November 29th, 2015 8:57 PM

I watched "Breakthrough" tonight and found most of it enjoyable, though nothing new really. But it appears that the FDA is open to consider Ageing as a disease which could help the pharmaceutical companies improve on Metaformin and others to overall improve ageing albeit slowly. I do think SENS will really be the treatment to make an impact, but if we can buy time for some of us older baby boomers an extra decade or so, I am all for it.

Also, just getting the idea of extending ageing as a possibility to the public, I think, is a positive thing. The concept is becoming less of a fringe of science (and science fiction) and more of another branch of science.

I did see that one person (I forgot his name in the show) quoting as increasing the average lifespan from 79 to 85 (maybe it was 84) years of age with new medicine. To be honest, it does not really excite me much. A few extra decades would be more reasonable (using their method of pills and slowing the ageing process) outside of the SENS rejuvenation method.

Posted by: Robert Church at November 30th, 2015 1:26 AM
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