A Journalist Once Again Fails to Mention SENS and Rejuvenation when Writing About the State of Longevity Science

The article on longevity science that I'll point out today continues a frustrating recent trend of failing to note one of the most important portions of the aging research field: SENS rejuvenation research. This is a puzzling omission, especially now that senescent cell clearance as a rejuvenation therapy is proven and heading for the clinic - a goal that SENS supporters have been advocating for fifteen years or so. For most journalists, there is no way to quickly and easily distinguish between any of the possible approaches to intervene in the aging process and thus extend healthy life. Being journalists, they are in the business of page views and rapid production of articles, not accuracy. So the typical approach here is to pull a half dozen of the options from the list and talk about them, giving them all equal weight. This is unfortunate, as the various lines of research leading to treatments for aging are far from equal in their challenges and their potential outcomes.

We can broadly divide the aging research situation into two camps. One the one side are ways to modestly slow aging, which is to say slow the rate at which molecular damage accumulates to cause dysfunction, disease, and death. Researchers investigate the operation of metabolism and try to alter it safely and beneficially. These research initiatives typically look like very traditional molecular biology and drug development programs, often pulling drugs from the existing stockpile because they might marginally impact the pace of aging. Attempts to recreate some of the health and life expectancy benefits of calorie restriction or exercise are a common theme, which if completely successful would add perhaps five to ten years to life span, if such a therapy was used throughout life. None have come even close to a fraction of that goal so far: the field is littered with expensive failures.

On the other side of the fence are ways to repair the molecular damage that causes aging, and here there are few limits to the years of additional healthy life that can be added. A repair can be carried out many times, after all. These therapies are as well defined as they can be in advance of their construction, or in the early stages of development in some cases: a mix of small molecule and other drug development to clear metabolic waste, gene therapies of a few varieties, and cell therapies to round out the mix. If repair of damage is complete and comprehensive, and carried out every few years, a person would have an indefinite life span - he or she would never get old, and if already old that burden could be reversed. The first prototype damage repair therapies will be far from complete or comprehensive, of course, but single treatments should produce outcomes that are large in comparison to lengthy periods of a treatment that merely slows aging. The more damage that is repaired, the better the result. Repairing the damage means actual rejuvenation: turning back the clock, trying to defeat aging, not just adjust the downward spiral a little.

For advocates who are trying to ensure that the research community adopts damage repair as the dominant strategy, it is frustrating to have the press telling the public that slowing aging is all there is, or painting specific efforts to slow aging (capable of extending life only a little) as being equivalent to specific efforts to reverse aging (capable of extending life greatly). The article linked here is a particularly egregious example of this sort of thing. It starts out and ends with quotes from people long involved in advocating and funding SENS rejuvenation research, and then completely fails to mention the SENS Research Foundation or the SENS approaches to repairing the damage that causes aging. The author wanders off on a tour of ways to slow aging as though that is the sum of the field. While I recognize that journalists, in their haste to fill the news hole, do this and worse to every topic under the sun, that doesn't stop it from being very annoying when it is a familiar, even important topic. It is vital to our future that repair of molecular damage becomes the mainstream of aging research as soon as possible, as that means the difference between living for a very long time in good health, or not achieving that goal. Unfortunately, for now and the foreseeable future that involves a reliance on philanthropic funding, as the mainstream of aging research is still set on slowing aging only. To the extent that journalists get everyone hyped up about lines of research - metformin, parabiosis, rapamycin, and so on - that cannot possibly produce large effects in humans, that damages the cause by producing cycles of hype and disappointment, an outcome that emerges precisely because people are not backing the right horse. Large effects are out there to be claimed, but not by merely slowing aging.

Adding ages: The fight to cheat death is hotting up

Michael Rae eats 1,900 calories a day, 600 fewer than recommended. He has been constraining his diet this way for 15 years. In some animals calorie restriction (CR) of this kind seems to lessen the risk of cancer and heart disease, to slow the degeneration of nerves and to lengthen life. Mr Rae, who works at an anti-ageing foundation in California, thinks that if what holds for rodents holds for humans CR could offer him an extra seven to 15 years of healthy life. No clinical trials have yet proved this to be the case. But Mr Rae says CR dieters have the blood pressure of ten-year-olds and arteries that are clean as a whistle. But his diet, and the life extension he thinks it might bring, are also a means to an end. Mr Rae, who is 45, thinks radical medical advances that might not merely slow but stop, or reverse, ageing will be available in the not-too-distant future. If CR gets him far enough to benefit from these marvels then a few decades of deprivation might translate into additional centuries of life. He might even reach what Dave Gobel, boss of the Methuselah Foundation, an ageing-research charity, calls "longevity escape velocity", the point where life expectancy increases by more than a year every year. This, he thinks, is the way to immortality, or a reasonable approximation thereof.

That all remains wildly speculative. But CR is more than just an as-yet-unproven road to longer human life. Its effects in animals, along with evidence from genetics and pharmacology, suggest that ageing may not be simply an accumulation of defects but a phenomenon in its own right. In a state of nature this phenomenon would be under the control of genes and the environment. But in a scientific world it might in principle be manipulated, either through changes to the environment (which is what CR amounts to) or by getting in among those genes, and the metabolic pathways that they are responsible for, with drugs. A treatment based on such manipulation might improve the prospects of longer and healthier life in ways that drugs aimed at specific diseases cannot match. Something which slowed ageing down across the board might fit the bill. And if it delays the onset of a range of diseases it might also go some way to reducing the disability that comes with age. An ongoing long-term study at Newcastle University has been looking at the health and ageing of nearly 1,000 subjects now aged 85. At this point they have an average of four to five health problems. None of them is free from disease. Most researchers in the field scoff at talk of escape velocities and immortality. But they take seriously the prospect of healthier 85 year olds and lifespans lengthened by a decade or so, and that is boon enough.

Before discovering whether anti-ageing drugs might be able to deliver such things, though, researchers need to solve a daunting regulatory conundrum. At the moment the agencies that allow drugs to be sold do not consider ageing per se to be an "indication" that merits therapy. It is, after all, something that happens to everyone, which makes it hard to think of as a disease in search of a cure, or even a condition in need of treatment. Unless ageing is treated as an indication, anti-ageing drugs can't get regulatory approval. And there's little incentive to work on drugs you can't sell. If regulators were to change their stance, though, the interest would be immense. A condition that affects everyone is as big a potential market as can be imagined. And there are hints that the stance may indeed be changing. Two existing drugs approved for other purposes - metformin, widely used and well tolerated as a treatment for diabetes, and rapamycin, which reduces the risk of organ transplants being rejected - look to some researchers as though they might have broad anti-ageing effects not unlike those claimed for CR.

The extent to which any of this technology will help will depend on how old those it is used on are when it comes into its own. The scope for radically changing the lifespan of a 65-year-old is much smaller than that of a 20-year-old, let alone an embryo. But the amount that is lost by getting things wrong goes up in exactly the same way. The idea that radical biotechnology can lead to longer lifespans than that of Jeanne Calment, a French woman whose recorded lifespan of 122 years has never been bettered, seems at best a plausible speculation. To say - as Aubrey de Grey, a noted cheerleader for immortality, has done - that the first person to live to 1,000 has probably already been born seems utterly outlandish. But thinking through Calment's life might give you pause. When she was born, in 1875, the germ theory of disease was still a novelty and no one had ever uttered the word "gene". When she died in 1997 the human genome was almost sequenced. All of modern medicine and psychiatry, barring general-purpose anaesthesia, was developed during her lifetime. If a little girl born today were to live as long - and why should she not? - she would see the world of 2138. The capabilities of medicine at that point will surely still be limited. But no one can guess what those limits will be.

It should go without saying, but sadly doesn't, that the scope for radically changing the lifespan of a 65-year-old is dependent on the degree to which the damage of aging can be repaired. Slowing the pace of aging is of no use to the old, those people who are already heavily damaged and failing, suffering and with a high mortality rate. If you want to rescue the old, and prevent people from becoming old and frail and in pain, then the only strategy that can deliver that result is repair of cell and tissue damage. This exactly describes the therapies laid out in the SENS vision, and which are presently under development in a few laboratories and companies. If we want a future of longevity and health, this seed must grow.

Comments

Two articles actually. They also did cheating death again no mention of sens.

Posted by: Steve h at August 12th, 2016 3:12 AM

I guess this state of partial media ignorance will persist until the results of a stage 1 clinical trial to remove senescent cells comes out. Hopefully it is Oisin who get there first rather than Unity, and they loudly trumpet that their therapy is part of the damage removal approach to aging. I've never seen the Unity people mention the SENS RF (although Judith Campisi is on their board of scientific advisors).

Posted by: Jim at August 12th, 2016 4:30 AM

The Economist mentions the Methuselah Foundation and Dave Gobel in the main article. What is the actual difference between the Methuselah Foundation and the SENS RF? I'd struggle to explain that.

They also mention that 'most researchers in the field scoff at talk of escape velocities and immortality'. This is the majority opinion at present unfortunately.

Posted by: jim at August 12th, 2016 7:24 AM

I dont think that is true Jim. I think certain people say researchers scoff at these things but the majority of researchers I encounter are perfectly happy with the idea of SENS or at the least increasing lifespan considerably. Immortality is in my view a daft word anyway and the press always use it either due to a lack of understanding or as I suspect an attempt to undermine efforts and make us look foolish.

I think this perception is circulated by the press and those with an agenda. Sure there are researchers who are adamamant it cannot be done but often in popular press articles these experts are rarely gerontologists and often they are not really qualified to speak on such matters.

Posted by: Steve Hill at August 12th, 2016 8:48 AM

Hi ! You bring an interesting/suspicious? omission to light (that rejuvenation is kept quiet to not alarm with false hopes/rejuvenation is still seen a bit like quackery because there is no tangible 'product' like rapamycin, metformin, all tangible stuff that back claims).

''Unfortunately, for now and the foreseeable future that involves a reliance on philanthropic funding, as the mainstream of aging research is still set on slowing aging only. To the extent that journalists get everyone hyped up about lines of research - metformin, parabiosis, rapamycin, and so on - that cannot possibly produce large effects in humans, that damages the cause by producing cycles of hype and disappointment, an outcome that emerges precisely because people are not backing the right horse. Large effects are out there to be claimed, but not by merely slowing aging.''

As some have said, I believe it is because it is not (yet) 'bankable'. So much of rejuvenation is paper theory and seen as 'fringe', that if
it concretizes (they must create something tangible very soon or else live in the shadows away from funding and to be just another 'fail attempt')
because true/truely age reversing methods will indeed reverse aging (still being in 'speculation' level is not helping SENS or any other rejuvenation
therapies; it's all speculation and it stays like that for too long (because of the slow pace/long time to build these therapies - it could be their problem)
(Time is money, money is time. Sure, I billionaire would 'buy' time by investing in SENS instead of dying rich (useless), but people are naturally
greedy and hold on to their cash - even over their own life. They will not invest a penny into something that is so Risk/Risky as rejuvenation therapies.
Their money could be thrown out the window - because they may have given money to - failed rejuvenation therapies in the past. Failure is a big
problem that rejuvenation therapies are facing : failure to work, failure to produce anything in the next 5 years, failure to do as planned, failure
to get the cash (humongous $$$ AdG is now aiming for millions of dollars/billions...way too much money in jeopardy = risk = fail. Fail when health has
spent 3 trillion dollars only to get Fail). But, also on this glaring omission problem, try to tell that to journalists who (understandably) may not
know the intricate differences between different hot terms such as senescence, glucosepane, AGEs or lipofuscin...or care either to know them. This fine detail lingo thus
becomes lost 'in translation'/muddied to journalists as mumbo jumbo that is 'all the same' as the CR terms and CR goals (in fact, some terms are
interchangeable, so all is mixed-up in one big fruit cake! And of course, SENS thus becomes another post-it/'just some other thing on the
Anti-Aging Post-Its List').

The only solution : create 1 single therapy that works in humans - tested and all. Make it happen, SENS - sooner than later (in 5 years tops and now we aleady on the 2nd year, time flies).
Or it will never happen (in our lifetime, too many hurdles : people fatalists 'not buying it' 'not buying something that is papertheory/air/fail risk', people exaggerating with 'overpopulation by lifespan extension/big ethical issues',
rejuvenation will remain sci-fi domain for At Least the next 5 decades or let's say 'therapeutical' not true rejuvenation that is not in our life time. The Ca$h needed for SENS is now billions dollars, that money will take the amount
of time it took for health sector (3 Trillion dollars can not solve death (though the methods never intended to unlike SENS which is based on a true fact that if All Damage is lowered repeatedely to a sustained comprehensive levels LEV/infinite lifespan is Very possible), why would crowd funded 20 thousand dollars would. It's like a drop in the ocean (needed to fuel this monumental endeavour). I'm not for all of that and remain hopeful/positive, but I realize these problems could be the nail in the coffin for rejuvenation.
I hope it isn't so. Fingers crossed.

Posted by: CANanonymity at August 12th, 2016 1:31 PM

In Reply to: jim at August 12th, 2016 7:24 AM
"...The Economist mentions the Methuselah Foundation and Dave Gobel in the main article. What is the actual difference between the Methuselah Foundation and the SENS RF? I'd struggle to explain that..."
===========
tl:dr Methuselah focuses at the cell and tissue level, while SENS focuses on the cell and smaller (molecular) level. YMMV.

Methuselah Foundation makes targeted angel investments in ventures that can't otherwise get funding but are near Development stage in the R&D continuum. Thus, we were first investors in Organovo (new parts for people) when no one else would give them a dime. They are now on the Nasdaq and sell 3d human liver assays and next month first in history kidney tissues for toxicology testing. I anticipate that next year they will introduce new tissue patches (perhaps skin and liver) for actual grafting into humans. New parts for people - if it's broke, replace it with new OEM parts. We were the first investor in Oisin as well and are now partnered with many other readers of Fight Aging as well as SENS Foundation in that investment.

Methuselah also makes small "proof of principle" grants such as to Ichor for C60 testing to work toward reproducing the original research and if that works, their creating a safe C60 product for sale. We also funded the sequencing and publishing of the Bowhead Whale genome. We also fund and operat three performance prizes, Methuselah Mouse prize, New Organ Liver prize, and are the operating partner with the NASA Tissue Engineering Prize (for microvascularization of engineered tissues). We are delighted to work with SENS foundation and support their work via donations each year and periodic support of SENS efforts via matching challenge grants.
Cheers,
Dave

Posted by: David Gobel at August 12th, 2016 3:03 PM

I think someone with an association to the SENS RF or Methuselah foundation should write to The Economist to point out that they failed to distinguish between the slowing aging and repairing damage approaches to life extension/rejuvenation biotechnology. Maybe contrast the severe limitations of the planned metformin clinical trial versus those of the upcoming senescent cell removal trials? Or talk about how treating congenital ND4 mitochondrial mutations in the eye with small molecule drugs is inherently limited versus Gensight Biologics stage 3 gene therapy for nuclear allotopic expression of the ND4 gene? They often publish these responses in their letter section, particularly if the respondent was mentioned in the articles (David Gobel, Michael Rae).

Posted by: Jim at August 13th, 2016 1:42 AM

I have another criticism of the article: the message sent by the illustrations. An exaggeratedly frail old looking guy acting energetic and happy? This is the misguided "you're as young as you feel" concept, a self deception to make us feel better about growing old. But we aren't fooled. The old guy in the illustration looks old! I trust this isn't what SENS has in mind. Damage repair should mean it won't be easy to guess a person's age.

Posted by: NY2LA at August 14th, 2016 6:59 AM

@David Gobel : Thank you for clearing up the different roles of Methuselah and the SRF. Both are important and should be supported by rejuvenation enthusiasts. Also great to learn about Organovo's upcoming plans, they're exciting. I believe once they out tissue grafting for humans, even more money will be poured into their field.

@Jim : That's a good idea. I think they'll give more weight to the comments of David or Michael as opposed to those of average readers like us.

@NY2LA : I agree, but then again, showing the picture of a happy 20 y.o. would be confusing for the readers - people still haven't wrapped their minds around the concept of rejuvenation.

Posted by: Spede at August 14th, 2016 5:24 PM

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