Faustian Bargains Struck in Search of Life Extension

It helps to know a little bit about the views of the author S. Jay Olshansky when reading this piece. He is one of the scientists behind the Longevity Dividend initiative, the goals of which can be summarized as greatly increasing government funding for current mainstream programs at the National Institute on Aging, with the aim of adding a few years to life expectancy over the next few decades. For those of us who seek far larger outcomes, and a way to turn back aging rather than merely slowing it down, he wishes us luck, but doesn't seem convinced that the goal of additional decades through rejuvenation research after the SENS model is practical.

Olshansky has long been vitriolically opposed to the "anti-aging" marketplace of the past few decades, packed as it is sellers of fraudulent pills and potions, and believes it a baleful influence that damages the prospects for serious science. You might look at the Silver Fleece awards that he conducted for some years, for example. I think that went a long way to determining his early position of opposition to SENS rejuvenation research and related advocacy for actuarial escape velocity, the unbounded increase in life span that would follow any meaningful first implementation of rejuvenation therapies. That is an opposition that has mellowed somewhat, though Olshansky clearly still strongly dislikes talk of radical life extension.

From my point of view, this unwillingness to seriously consider sizable outcomes and potentials is a part of the problematic legacy of the last generation of researchers in this field. It is why they suppressed interest in efforts to treat aging as a medical condition. It is why they failed to make significant progress despite all the evidence in hand pointing to the causes of aging. It is why people like Aubrey de Grey and others involved in SENS had to come in from outside the field to shake things up.

The story of Faust has become a metaphor for a promise or tradeoff that at first seems appealing, but with time is revealed to be a bad bargain. The story of human aging and the modern rise in longevity has remarkable correlates to the story of Faust, but with some interesting twists. Here's the connection. The first longevity revolution that began in the middle of the nineteenth century occurred primarily because of gains made against infant and child mortality resulting from advances in basic public health. This was followed by reductions in death rates from cardiovascular disease late in the twentieth century. A quantum leap in life expectancy of 30 years ensued at lightning speed. Nothing in history has ever come close to the magnitude of this benefit to humanity. While there is no disputing the value of life and health extension from the first longevity revolution, rarely does something so desirable come without a Faustian-like price.

Along with 30 years of additional life and the opportunity to see almost all our children live long enough to have families of their own, humanity also witnessed a subsequent dramatic escalation in the prevalence of age-related chronic, fatal and disabling diseases and their attendant costs and heartache. That is, we now live long enough to experience the aging of our bodies. In retrospect, it was worth every part of the bargain. But Mephistopheles isn't done with us. Like a street magician that lets you win the first game, and then sucks you into a bigger con with larger stakes, or a drug dealer that gets you hooked with free samples, the next much costlier offer is before us now. We've had our taste of longevity, but now we want more - much more at any cost, and Mephistopheles knows this.

With life itself as the most precious commodity there is, it's easy to see the next con. The first is the rise of what has become known as the antiaging industry - a multibillion dollar enterprise designed to convince us that the secret to the fountain of youth is already within our grasp. Pay dearly for their elixirs now and wait for the promise of a longer life to appear decades later. What do you think the chances are that your investment will pay off? The catch is that the alleged benefits don't appear, if at all, until after the longevity salesmen has left the scene and pocketed your cash. What's different today from the cons of the past is the rise of the scientific study of aging and genuine opportunity offered for healthy life extension. The modern practitioners of anti-aging medicine try and sell the public what appear to be genuine scientific interventions based on real science, before they're proven to be safe and efficacious: "whenever science makes a discovery, the devil grabs it while the angels are debating the best way to use it."

The second response to an insatiable desire for more life is also predictable, but the danger could be an even worse Faustian bargain than that posed by the antiaging industry. The method used to manufacture the first longevity revolution is known as the "infectious disease model" - that is, as soon as a disease appears, attack it with everything in the medical arsenal. Beat the disease down, and once you succeed, push the patient out the door until they face their next challenge; then beat that one down. The formula is simple - repeat until failure. This model was perfect for infectious diseases and effective at first for chronic degenerative diseases, and no doubt there is still progress to be made, but evidence has emerged that this approach is likely to run out of steam. The application of an infectious disease model to chronic fatal and disabling diseases associated with aging is Mephistopheles latest "bargain." The irony behind this new bargain (otherwise known as the current medical model of disease) is that the medical community advocating for disease eradication doesn't even recognize the health consequences of success.

The bargain today is crystal clear - we're being offered incrementally smaller amounts of survival time at a very high cost, and the prospect that most of the additional months and years of life will be riddled with frailty and disability. Keep in mind that the human body has no designer; it was not constructed for long-term use; and our Achilles heels are already visible - neurological conditions such as Alzheimer's disease and related conditions are associated with non-replicating neurons; and muscles and joints have a difficult time navigating the ravages of biological time. The Faustian bargain before us now is, in exchange for small doses of additional life, humanity will experience a suite of fatal and disabling conditions expressed at later ages that rob us of what we hold most precious - our mental and physical functioning.

What's the solution? Don't sign the contract! A clue about what we should do instead was presented to us decades ago. In the mid-1950s, it was suggested that attacking aging itself rather than the diseases associated with it offered the greatest hope in warding off the infirmities of old age. In 2006, my colleagues and I extended this line of reasoning by coining the phrase "the Longevity Dividend" to describe the economic and health benefits that would accrue to individuals and societies if we extend healthy life by slowing the biological processes of aging. This idea was distinctive because we proposed to extend healthy life by shifting our emphasis from disease management to delayed aging. Recent advances in biogerontology suggested that it is plausible to delay aging in people. For example, "senolytics" may offer a unique opportunity to forestall the ravages of aging through the systematic elimination of cells that are still alive, but which no longer function normally.

The Longevity Dividend is an approach to public health based on a broader strategy of fostering health for all generations by developing a new horizontal model to health promotion and disease prevention. Unlike the current vertical approach to disease that targets individual disorders as they arise, the Longevity Dividend model seeks to prevent or delay the root causes of disease and disability by attacking the one main risk factor for them all-biological aging. Evidence in models ranging from invertebrates to mammals suggests that all living things have biochemical mechanisms influencing how quickly they age, and these mechanisms are adjustable.

Slowing down the processes of aging - even by a moderate amount - will yield dramatic improvements in health for current and future generations. Advances in the scientific knowledge of aging may thus create new opportunities that allow us, and generations to follow, to live healthier and longer lives than our predecessors. By embracing a new model for health promotion and disease prevention in the twenty-first century, we can give the gift of extended health and economic wellbeing to current and all future generations. What is the cost of this new more effective model of primary prevention that will save the world trillions in health care costs? A fraction of the basic research cost required to create sixth generation fighter jets; or the salary from just one quarterback in the National Football League.

Link: https://doi.org/10.3389/fmed.2017.00215

Comments

Steve,

Too conservative for me too. But this essentially fits the narrative of the mainstream science in this field, while sating the concerns of the ethicists that want us to die on time, and not actually extend lifespan.

Posted by: Ham at December 18th, 2017 10:07 AM

"In 2006, my colleagues and I extended this line of reasoning by coining the phrase "the Longevity Dividend" to describe the economic and health benefits that would accrue to individuals and societies if we extend healthy life by slowing the biological processes of aging. This idea was distinctive because we proposed to extend healthy life by shifting our emphasis from disease management to delayed aging. Recent advances in biogerontology suggested that it is plausible to delay aging in people. For example, "senolytics" may offer a unique opportunity to forestall the ravages of aging through the systematic elimination of cells that are still alive, but which no longer function normally."

I was amused by this part. He is advocating for slowing aging while the example he gives is really a reversing aging approach ;)

Maybe I misundertood him and he equates "slowing aging" to "removing aging damage"? Just below he negates that possibility:

"Evidence in models ranging from invertebrates to mammals suggests that all living things have biochemical mechanisms influencing how quickly they age, and these mechanisms are adjustable. Slowing down the processes of aging - even by a moderate amount - will yield dramatic improvements in health for current and future generations."

Are we witnessing the exact moment of a shift in mentality among the Longevity Dividend group from a "gerontological" approach to a "damage-repair" approach?

Posted by: Antonio at December 18th, 2017 12:04 PM

@Antonio, maybe, but not too much. The main idea is the same 'delaying ageing' or 'slowing' -- not reversing. When we remove some damage we reverse associated pathology. That is all. His view is not merely 'too conservative', hovewer, it is dangerous because he spends money on useless approach!

Posted by: Ariel at December 18th, 2017 12:15 PM

I am not sure that's true Ariel, if he is advocating senolytics as as healthspan measure, it is no different to us advocating the same treatment for health and lifespan.

As it happens senolytics on its own is likely to be healthspan only, going on mice results, but it is effectively damage removal, so it fits with both approaches.

It will be perfectly possible to sell individual therapies for healthspan, whilst also pushing the needle on lifespan. Not all of course, because metabolic measures only push out lifespan incrementally, but there are many therapies that will be useful for both, and it will be difficult for the non specialist to say which is which.

From this article we can say that opinion is shifting in the right direction, I'm not too worried about misspent research funds, so long as more of the funds go in the right direction, and that is obviously happening with senolytics.

Posted by: Mark at December 18th, 2017 12:37 PM

@Mark, I only mean that the final goal is matter. The line is clear. If senolytics will add 5 years to people average lifespan, for many like him it will be more than enough, but for us it is the beginning. To allow real whole-body rejuvenation we need to fix all the damage.

Posted by: Ariel at December 18th, 2017 1:06 PM

Ariel: I'm not sure Olshansky is aware of the difference, but senolytics are very different from his traditional approach, namely slowing damage accumulation, while senolytics leave damage accumulation mechanisms alone and instead periodically remove the accumulated damage. The former approach quickly reaches diminishing returns while the latter approach can theoretically continue forever, and thus the consequences for life expectancy are very different.

Posted by: Antonio at December 18th, 2017 1:31 PM

Hi there ! Just a 2 cent,

''The Faustian bargain before us now is, in exchange for small doses of additional life, humanity will experience a suite of fatal and disabling conditions expressed at later ages that rob us of what we hold most precious - our mental and physical functioning.
What's the solution? [Don't sign the contract!] A clue''

You had me at 'a clue', as in get a clue. I don't know why it is so hard to get.
Clueless. So thick.

''By embracing a new model for health promotion and disease prevention in the twenty-first century, we can give the gift of extended health and economic wellbeing to current and all future generations.''

I forced myself to read further, that is nice but is Not a gift, or rather it's a wrapped gift that contains poison/'wrapped' in disguise - just as much Faust devil itself and Faux. The fact is, you die anyway, that's the fact that they omit and just want people to accept defeat/die when they could live longer and Healthier TOO - both; not just one or the other, and certainly not die 'on clock' like everyone else.

For me it is, from one side, just utter nonsensical and, the other, utter nobrainer, that they still don't get it or rather they do - but they play 'by the rules'/think there is no solution except slowing aging/betterment of health and die all happy; and from the other side, that rejuvenation is currently the only solution; respectively.

Let me talk to these people, they will change their minds, they need someone who lived and (nearly) died to understand why you Don'T want to die, live however long you Can/yes taht means past any human limit whatosever if possible and certainly notlittle crumbs of 'healthspan' because it will 'reduce economic burden'... Thank God for that b ecause obviously your life is made to reduce economic burden, or what little time you will have 'more' with this self-defeating approach of 'lets patch/slow aging slightly and give you healthy years, un return you reduce economic burnder, how's that'..I can get better results than that taking metformin, doing exercice, diong CR, drinking red wide resvertrol quercetin, eating supplements, antiaging stuff, and make push ups in my home - and get a GOOOD solid 5.5 to 9.3 years extra of health - which will miraculous as will age healthy. So then I can make mea culpa and die at my 100 years. Oh I contributed to reduce economic burden/tax down

That's waht he means by Faustian Bargain...yes I understood it means you are f...with their approach and it is the poor approach of just improving health; it' stpid beyond words because it comepletely omits the dying part or rather acknowledging it; and saying nothing about it but...'but it's like that...nothing you can do about it....you die one day before 122, accept it and don't be afraid; let death be accepted and you will like 'healhty years' until it 'ends' one day (before 122)'.

I'm sure if AdG came and said look we offer you 300 years, will you take it :

''No. Economic burden too high - Me Want to die. 122. perfect number'.

(sigh)
Just a 2 cent.

Posted by: CANanonymity at December 18th, 2017 9:57 PM

I always find it interesting to read an interpretation of my views written by others. The first paragraph of this essay was apparently written by someone who does not really know me, nor have they actually read my work carefully. Here's the problem.

"It helps to know a little bit about the views of the author S. Jay Olshansky when reading this piece. He is one of the scientists behind the Longevity Dividend initiative the goals of which can be summarized as greatly increasing government funding for current mainstream programs at the National Institute on Aging, with the aim of adding a few years to life expectancy over the next few decades."

There is nothing in my work indicating that the focus is on government funding for current mainstream programs at the NIA. I don't care where the funding comes from, nor am I particular about the direction of the research. I'm fine if Aubrey's approach works -- it doesn't matter to me. The LDI is all about fundamentally shifting our emphasis from diseases toward biological aging -- recognizing that this is the greatest risk factor for what goes wrong with us as we grow older. Mention of senolytics in this article is just one example that I happen to like -- I have no vested interest in any one particular approach.

As for those advocating for much higher life expectancies in national populations, I would direct your attention to our Science article in 1990 where we describe entropy in the life table. Nothing has changed since then, and contrary to the view presented in this article, my view of this issue has not changed. There is no reason why death rates can't decline further; and I see the possibility of altering the slope of the intrinsic mortality curve; but much higher life expectancies require a unique set of circumstances that are apparently only visible to those who work with life tables.

Also, contrary to the view of some that life expectancy will continue to rise indefinitely, there is now compelling evidence indicating that the rise in LE is not only leveling off, in parts of the world (and for certain subgroups), it's actually declining.

We have a lot of work ahead of us to convince the public health community that modulating aging is the new form of Primary Prevention. I see no need to exaggerate the consequences of success. Indeed, at a meeting that Aubrey and I just attended in Madrid, he assured me that he doesn't exaggerate because he never talks about immortality. Then, at the end of the meeting when it came time to make predictions about the future, he indicated that death would no longer occur after ~2060 (right Aubrey?). I found that quite amusing.

Posted by: Jay Olshansky at December 19th, 2017 11:08 PM

Thanks for your reply, Dr. Olshansky.

So do you think that even if SENS work, it will increase lifespan only by a few years? Or you simply don't think it will work or can be implemented in this century?

In the first case, why will we die so soon, if aging damage would be always below pathogenic levels?

Posted by: Antonio at December 20th, 2017 12:22 AM

The paper uses two major methods to compute the likelihood of changes in life expectancy, each based on a different assumption.

One of them assumes that any possible antiaging therapy must be more or less equivalent to curing the major age-related diseases, or put differently, any therapy that does more than that is highly unlikely. But actually there is no basis for that assumption. Indeed, a working panel of SENS therapies would also address things like TTR amyloidosis, that is minor for current populations but appears to be the main cause of death of supercentenarians (and actually SRF has funded TTR amyloidosis research, apart from funding more major diseases' research like cancer's).

The other assumes (again at face value) that the mortality rates will still follow a Gompertz law with the same mortality rate doubling time. This will not hold for a comprehensive panel of working rejuvenation biotechnologies, that would produce a basically flat mortality curve. Even not so comprehensive therapies could produce a Gompertz curve but with higher doubling time.

Posted by: Antonio at December 20th, 2017 4:39 AM

Also, Dr. Olshansky: where in the world is the rise in LE leveling off or declining?

Using data from the Human Mortality Database, I obtain a different picture in Europe and the US:

http://s17.postimg.org/v0ib9keyl/Sweden.png

https://s4.postimg.org/40k48iwgd/France.png

https://s11.postimg.org/csib4flcj/Spain.png

https://s30.postimg.org/6fzmcgb9t/USA.png

https://s21.postimg.org/iavzq5xbb/all.png

By "the total life expectancy at age x is y" I mean "the life expectancy at age x is y-x". I don't know if it's the correct term.

Posted by: Antonio at December 20th, 2017 5:42 AM

Dr. Olshansky is interested in 'fundamentally shifting our emphasis from diseases toward biological aging -- recognizing that this is the greatest risk factor for what goes wrong with us as we grow older.' That makes him a great guy and an ally to the cause in my book.

I'm inclined to think changes in life expectancy will be big discontinuous jumps upwards rather than a more gradual increase; I generally think these sort of big, abrupt changes will be the defining characteristic of the 21st century - but time will tell who is right.

Posted by: Mark at December 20th, 2017 2:23 PM

Mark,

Do you think so? Because in regards to something like senolytics, I keep seeing more and more articles that talk about them, but stress that they're not designed to increase how long we live. I don't know if that is PR speak to not frighten the masses or to quell the concerns of the all important 'ethicists', or if it's bad reporting due to not understanding the topic, or if it's just a guess as to their effect as a stand alone treatment.

This article I saw today: http://www.bbc.com/news/health-42273362

"Unity Biotechnology, in California, is planning to begin human trials next year of a drug to clear senescent cells from the knee.

Dr Jamie Dananberg, chief medical officer, told me: "Osteoarthritis is a key reason why it hurts to get old. Our hope is that a single injection will alleviate pain, halt and perhaps even begin to repair the knee."

Even if the drug, which might need to be injected every few months, was partially successful, it could have huge implications for improving quality of life for those affected.

Unity is also targeting eye, lung and kidney disease.

These drugs are not designed to make us live longer, but to make old age less painful and more healthy - to put more life in our years. "

I mean, if given the choice I'd prefer increased healthspan over what we have now, but I, like many others here are looking for a little more than that. I'd like to think that with even a couple treatments, your expectancy(not span 122yrs) would definitely go up. Who knows.

Posted by: Ham at December 20th, 2017 3:02 PM

"to put more life in our years"

The old motto... Aubrey has a paper critizicing it.

Posted by: Antonio at December 20th, 2017 4:46 PM

@Ham

Hi Ham ! Just a 2 cent,

'' I keep seeing more and more articles that talk about them, but stress that they're not designed to increase how long we live. I don't know if that is PR speak to not frighten the masses or to quell the concerns of the all important 'ethicists', or if it's bad reporting due to not understanding the topic, or if it's just a guess as to their effect as a stand alone treatment.''

I would wager it's a mixture of all thjose things...but the latter point is the closest reason, or rather they don't guess but rather know. In general, studies with senescent cell cleareance have been favorable by reducing inflammation (less senescent cells, less SASP), this improves health strongly (it only takes a tiny % of senescent cells to cause inflammatory SASP havoc).
What they also know is that senescent cell clearance has not been met with extreme lifespan extesion. And that's because you have 'the rest'...all other damages, junk and what not.
Also taking quercetin and dasatinib and other senolytic helps but just because you drink red wine or take dasatinib does not stop the complications, it slows them. Senescent cell removal is like putting a plaster on a wound, it does not stop more senescent cells from coming (not solve teh proble at the source (inflammation is the problem (SASP by them) but there is a reason/explanation they are entering senescence in the first place and it is not just because of the surrounding SASP, SASP is contributory but not the whole picture, something that can bring you to SASP in the first place and then SASP by the senescing cells exhacerbates whole thing in a vicious self-destructive circle), it is a temporary relief but can be continuous if you keep on doing it thus it becomes a viable solution), it reduces the load/burdern/their amount thus makes them inconsequential by reduction of their numbers.
For example, one study in P16 ink4 mouse found healthspan extension (20% or so) by ablation of p16 senescent cells in them. This is theclosest you will get in terms 'what effect' wil happen if senescent cells are removed. But, in humans, it is always weaker (generally) than in mice, so that effect will be helpful, but a bit less. Thus, we can sort of do conjecture, ballpark figure would be something like 5-15 years, 10y avg for that one therapy of senscent cell ablation and the 7-therapy combination would yield 10-30 years extra of healthspan (see my previous comment that went it very deep detail why). This could also 'overlap' on the maximal lifespan allowing the most genetically gifted (like those coming from centenarian families) to beat the 122 to say about 130-150 or so but not much more (because of cell limits and other defects (like heart TTR in supercentenarians, though that will be solved once protein aggregates are removed by a therapy)). We also have to remember that by the 10th decade, aging accelerates dramatically (upward 5-10 fold as such your chances of dying in 'this decade' are 99.998% sure).

The combination of the therapies will definitely extend lifespan, and healthspan. It may not be very 'obvious' when you do these theapires, akin to doing CR, you feel better, sleep better etc...feel healthier but it is not like you Re-Juvenated by 30 years in your face either...
CR can make you about a decade or so younger in the face/skin and it shows.
But there are other limits that could hinder this (replicative senescence, telomere loss/chromosomal laxing, histone loss, demethylation of centromere/sub-telomere/telomere, epigenetics (which would replace themselves if repairs are made but there is not much on that other than global methyl levels back to younger levels) and make us not go (much) above the maximal lifespan (150 max).
The replacement of organs/tissue is a solution but it is total replacement A to Z (except brain portion like your cortex and other precious memories that define you), not partial, tis would circumvent limits. It is still great to know that you could possibly live 122 years nearly 100% healthy. I'm like you I think it s*cks that there is so much focus on dying and just accepting it like that when we are so close to reach a milestone. I would wager that by SENS, the advancement of humanity/life has made leaps and bounds because of him/his project; reading his LEV paper just 30 or 40 years ago would be like a bad joke, yet here we are and the prospect of much longer lives are real. Why is there so much hate...because it never happened before and could/might be possible now and not science-ficntion anymore. Thus, like you said, medias try to say it does not work or will not do anything - to not frihten the people or give them false hope or 'Immortality 2' Coming Soon To A Clinic Near You TM'. See what I mean, people see that and laugh their asses off because it's not serious. Except, we are, and that's why it is bothering them because we have proofs and no time for words; life is short, the therapies (and the funds for them) must happen (and ethicists must side step this one because unlike they think we are 'blind to the 'obviousness' of dying and being good by dying as a good human, dead'...), must happen now (or soon(er)).

Just a 2 cent.

Posted by: CANanonymity at December 21st, 2017 3:20 AM

Antonio, the view of one of Jay's co-authors (and Jay's perspective might be similar) of the 1990 paper seems to be that aging-caused disease cannot be eliminated (and consequently there can be no dramatic lifespan extension) and only human clinical trials proving the opposite could change that view.

Posted by: Florin Clapa at December 21st, 2017 1:14 PM

I don't know what the effect of SENS will be on population-based life tables and life expectancies for national populations -- nor does anyone else. What I'm opposed to are people who make up future life expectancy numbers based on science that hasn't been done yet, and without a clue as to how these population based metrics are calculated.

Let's be clear -- radical life expectancy increases in long-lived populations requires dramatically accelerating reductions in death rates from all causes combined (total mortality). While not impossible, it does require that we generate/manufacture survival time for older people in the future faster than we did for children in the early 20th century. If you understand exactly how and why the first longevity revolution occurred, you'll realize just how difficult this will be. One important factor that gets in the way is extrinsic mortality, which isn't going away even with modified aging therapies, so the mathematics of the life table combined with genetic heterogeneity first and foremost makes it highly unlikely this could occur in our lifetime.

I've some some in the radical life extension community just draw straight line death rates for people of all ages in the future, as if we can create a mortality schedule for humans of all ages that resemble that of teenagers or cold water fish. This is a fun exercise to do with a ruler, paper and pen, and it makes for good science fiction, but there is nothing indicating that this is even remotely possible in humans. Keep in mind that even if SENS works, and I hope it does, no one will really know the effects on national population vital statistics like life expectancy for quite some time -- so you can't even generate proof of radical life extension even in the presence of such an intervention.

There is no need to exaggerate the consequences of success. Even a minor success in modulating aging will have a dramatically positive impact on healthy lifespan and the global economy. If we live longer, and I believe we will, that'll be the bonus. Just please stop making up numbers because you want to believe it to be true -- it gets in the way of those of us trying to drum up funds to accelerate the very aging science we all believe is both wanted and needed.

Posted by: S. Jay Olshansky at December 21st, 2017 4:16 PM

"One important factor that gets in the way is extrinsic mortality, which isn't going away even with modified aging therapies"

Extrinsic mortality alone, with no aging, would produce the mortality rates of people in their 20s or 30s, and thus a life expectancy of thousands of years. That's where the "the first 1000-year old person is already born" comes from. So no, extrinsic mortality will not get in the way if effective rejuvenation therapies are developed. Of course, SENS 1.0 will not eliminate aging entirely, but that is not really needed, only to reach and maintain longevity escape velocity (and once reached it gets easier and easier over time).

You can find a more detailed analysis here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267031/

"Keep in mind that even if SENS works, and I hope it does, no one will really know the effects on national population vital statistics like life expectancy"

If you remove the aging damage of a 90-year old so that it's similar to that of a 60-year old, obviously you will obtain the similar death rates to that of 60-year olds (unless you think that aging is programmed and not a consequence of damage). So the effect on life expectancy can easily be predicted (or at least the programmed vs non-programmed debate be ended).

"Just please stop making up numbers because you want to believe it to be true"

Please stop making strawman arguments like this one.

Posted by: Antonio at December 21st, 2017 6:07 PM

Wow, this will be my last comment on this thread. I don't know Antonia, but clearly this person does not understand life tables. Where in the world does this person come up with the conclusion that extrinsic mortality will yield death rates for people in their 20s and 30s? Extrinsic mortality occurs throughout the lifespan (including congenital anomalies early in life that remove a large number of PYLs); it permanently removes person years from a period life table; and once they're gone they're gone forever when calculating period life expectancy; so no, a 1,000 year old person already born is one of those nonsensical statements I've heard repeatedly from those who simply don't understand population based metrics.

The concept of actuarial escape velocity is voodoo demography -- does anyone really take that seriously? It's not quite as bad as extrapaholics as Aubrey likes to call them (I agree with him completely on that), but it's close.

On the last point, transforming the death rate of a 90 year old into that of a 60 year old requires the removal of nearly four doublings. My guess is that you've never bothered to look at a life table to see the difference in death rates between these two groups; nor do you apparently realize that the doubling time for the death rate has never changed in humans; ever.
If, if, if, if you could only do this, then that would happen. Sure -- draw it on a piece of paper and type it into your computer -- that's the easy part; making it happen in the real world; that's the challenge. Again, please stop making things up -- either we're talking science or we're not. Talk about a straw man argument. Perhaps Antonia would like to identify him/herself???

Posted by: S. Jay Olshansky at December 21st, 2017 8:47 PM

@S. Jay Olshansky: Debating is somewhat fruitless when your axioms differ. The best you can do is collaborate to understand how they differ.

I believe I understand most of yours, the relevant ones of which here are that (a) anything lacking published data isn't worth debating when it comes to effects on life span, and (b) lack of progress to date despite considerable effort indicates that life extension is a hard problem on all fronts (versus the alternative possibility of the approaches taken being poor).

One of our axioms is that this is a problematic viewpoint, as in a time of development we should be assessing expectation value to steer research directions, not trampling forward blindly and only assessing in hindsight. It is perfectly reasonable to try to assess likely sizes of outcomes ahead of time, and adjust based on data as it comes in. Especially given that arriving at published data for SENS-like approaches should be fairly cheap in comparison to building viable calorie restriction mimetics, given the records of expenditure and progress to date on both sides. Indeed, we could put off discussion for the few years needed to obtain human data from the first senolytics, which should go a long way to setting the terms of the debate for the next decade.

My prediction is that it is likely the mouse-human relationship in results for senolytics will be quite different from the mouse-human relationship for the other few items we have data for, e.g. calorie restriction and growth hormone receptor dysfunction. They will be different because senolytics are a form of damage removal, while the other two are both tinkering with evolved plasticity in pace of damage accrual in response to environmental circumstances. Not the same at all.

Posted by: Reason at December 21st, 2017 9:42 PM

Hi all, just a 2 cent, (I'm not scientist or anything, just visitor keeping (CAN)anonymity privacy)

I think that it will be an enormous mountain to climb to be able to make the elderly people over 90 to have mortality of that of people in their 60s, as at this late point of 90 y it is almost game over but if you start earlier in life (before 40-60 year old) with the therapies, then the curves would change (we hope). I think the secret is that you would keep a young biology much longer and some of the earlier mortality in very young people will be cured (or let's say it will be reduced, as such even less young people will die 'too early' if they get SENS the quickest possible in their lifespan. The sooner the better, thus children will also reap from it and this will affect the mortality curves). Currently, the numbers are very telling but they are lack this element of lifespan elongation, the therapies, once we know the effect in mice and see this transposed (albeit less) in humans; the changes will happen (including the mortality curves). It may not allow poeple reaching a 1000 years old (because of cell limits), but much more people will end up in the 10th decade bracket and thus mortality curves will be reduced and then ahve sharp increase in the 10-12th decade (of course that is conjecture but mice are not conjecture they are real and humans ar too, we might not have the same results, but mice a re a decent model to build on; and then we will see this how it plays out in humans and other apes (SENS should do dstudies on Apes/long lived animals and study the results over 'smaller periods of time' (like 5 years or so to get a brief mortality portrait), this will answer this matter of mortality curves and show if yes, we will live to 120 or no, it makes no difference on diseases - which, from biological point, is untrue as it would help - if you stop senescence it will have a large impact. SENS targets things very very specific that are linked to aging and diseases *unlike anything on the market right now (the rest are metformin, CR, and other metabolism approach that are dead ends but still better than nothing) - which are the elements/factors responsible behind these curves. If these factors are changes (which SENS will do, in theory, if it works as planned then yes you will see a change). This is Already visible with CR (Calorie Restriction) in apes where there is reduced mortality over a long term, but people ingeneral do not do CR as such the curves are barely changed. They do not take account of the future therapies effect on them, which well be Sizeable if done correctly from a younger age in a very large population, just like CR does. The point is that the interventions should alter the population dynamics and mortalities in some way; if it works as planned. And since it Does work in mice - because we share the same biology but with differences, it is a tell-tale sign of things to come :)).

Just a 2 cent.

Posted by: CANanonymity at December 21st, 2017 10:12 PM

Wow, what an interesting commentary for this subject, specially towards Jay.

I do find it hard to believe that with

1. Nanotechnology coming on line in the next decade or so (nanobots?)
2. Genome, analyzing all the big date that should yield something useful.
3. AI also coming on line in the next decade which should facilitate and expedite the longevity knowledge.
4. Also, if anyone believes knowledge (including our own biology) is exponential, this should also help the cause greatly.
5. And, the first step directly (we all assume) is senolytics which is expected to be available within 5 years, at least via medial tourism. This right here gets us 5 more years of life if the assumptions are correct.
6. Artificial organs (repopulating animals organs and or 3D printing)
7. Robotics same as AI, to expedite longevity project.

I also want to point out what Ray K mentioned numerous times (I am sure you heard his example before) regarding that the data and medical scientists expected the deciphering of the genome would take much long when they go to 1% done. But Ray knew the project was on target and budget. But the "experts" believed it would take longer and cost more.

I may not be as smart and knowledgeable as Jay, but I can not believe we will not move aging knowledge significantly over the next few decades. I think the biggest hurdle is getting more people on board, and more funds.

BTW, when someone says you can not do something, they are right, THEY don't know how to do something.

As CANanonymity says, my 2 cents worth.

Posted by: Robert at December 21st, 2017 11:21 PM

Well, if it's your last comment, I will not bother to write a detailed reply. Anyway, there is not much to reply to, only things like "you have no idea" and "it hasn't happened before". I'm still waiting the answer to where in the world the rise in LE is decreasing, but I suppose it will not come.

Posted by: Antonio at December 22nd, 2017 12:17 AM

IMO, computing power and AI will get us there.
"Another way to think about Moore's law is to apply it to a car. Intel CEO Brian Krzanich explained that if a 1971 Volkswagen Beetle had advanced at the pace of Moore's law over the past 34 years, today "you would be able to go with that car 300,000 miles per hour. You would get two million miles per gallon of gas, and all that for the mere cost of four cents."

Posted by: Lee at May 23rd, 2018 8:44 AM

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