A Lightning Tour of One Arm of the Longevity Science Community

This popular press article covering one arm of the longevity science research community in the US is better than most, in that it seems moderately accurate when it comes to identifying some of the people who matter and a few of their views on the topic. Of course in any such article you are flying over the terrain at a great height, seeing only the mountaintops, and little of what really makes the place live and breathe. You are also missing the other regions you cannot see. My chief complaint here is unfortunately a typical one, in that the author presents the SENS rejuvenation research program in a fairly disingenuous way. This is no way to treat the class of research and development most likely to turn back aging in the near future.

For decades, the solution to aging has seemed merely decades away. In the early nineties, research on C. elegans, a tiny nematode worm that resembles a fleck of lint, showed that a single gene mutation extended its life, and that another mutation blocked that extension. The idea that age could be manipulated by twiddling a few control knobs ignited a research boom, and soon various clinical indignities had increased the worm's life span by a factor of ten. Death would no longer be a metaphysical problem, merely a technical one. The celebration was premature. Gordon Lithgow, a leading C. elegans researcher, told me, "At the beginning, we thought it would be simple - a clock! - but we've now found about five hundred and fifty genes in the worm that modulate life span. And I suspect that half of the twenty thousand genes in the worm's genome are somehow involved."

For us, aging is the creeping and then catastrophic dysfunction of everything, all at once. Our mitochondria sputter, our endocrine system sags, our DNA snaps. Our sight and hearing and strength diminish, our arteries clog, our brains fog, and we falter, seize, and fail. Every research breakthrough, every announcement of a master key that we can turn to reverse all that, has been followed by setbacks and confusion. A few years ago, there was great excitement about telomeres, DNA buffers that protect the ends of chromosomes just as plastic tips protect the ends of shoelaces. As we age, our telomeres become shorter, and, when these shields go, cells stop dividing. If we could extend the telomeres, the thinking went, we might reverse aging. But it turns out that animals with long telomeres, such as lab mice, don't necessarily have long lives - and that telomerase, the enzyme that promotes telomere growth, is also activated in the vast majority of cancer cells. The more we know about the body, the more we realize how little we know.

In the murk of scientific inquiry, every researcher looks to a ruling metaphor for guidance. Aubrey de Grey likes to compare the body to a car: a mechanic can fix an engine without necessarily understanding the physics of combustion, and assiduously restored antique cars run just fine. De Grey is the chief science officer of Silicon Valley's SENS Research Foundation, which stands for Strategies for Engineered Negligible Senescence - a fancy way of saying "Planning Your Comprehensive Tune-up." De Grey has proposed that if we fix seven types of physical damage we will be on the path to living for more than a thousand years. "Gerontologists have been led massively astray by looking for a root cause to aging, when it's actually that everything falls apart at the same time, because all our systems are interrelated. So we have to divide and conquer." We just need to restore tissue suppleness, replace cells that have stopped dividing and remove those that have grown toxic, avert the consequences of DNA mutations, and mop up the gunky by-products of all of the above. If we can disarm these killers, de Grey suggests, we should gain thirty years of healthy life, and during that period we'll make enough further advances that we'll begin growing biologically younger. We'll achieve "longevity escape velocity."

De Grey vexes many in the life-extension community with his prophetic air of certainty. His 2007 book, "Ending Aging," is replete with both exacting research into the obstacles to living longer and proposed solutions so ambitious that they resemble science fiction. De Grey's fix for mitochondrial mutation, for instance, is to smuggle backup copies of DNA from the mitochondria into the vault of the nucleus, which evolution annoyingly failed to do-probably because the proteins needed in the mitochondria would ball up during their journey through the watery cell body. His fix for that, moving the DNA one way and the proteins that it produces another, amounts to a kind of subcellular hokey pokey. A number of scientists praise de Grey for anatomizing the primary threats, yet they see troubleshooting all seven pathways through such schemes - and you have to troubleshoot them all for his plan to work - as a foredoomed labor. Biogerontologist Matt Kaeberlein said, "It's like saying, 'All we have to do to travel to another solar system is these seven things: first, accelerate your rocket to three-quarters of the speed of light... ' "

Ned David is a biochemist and a co-founder of a Silicon Valley startup called UNITY Biotechnology. UNITY targets senescent cells - cells that, as they age, start producing a colorless, odorless, noxious goo called SASP, which UNITY's researchers call "the zombie toxin," because it makes other cells senescent and spreads chronic inflammation throughout the body. In mice, UNITY's treatments delay cancer, prevent cardiac hypertrophy, and increase median life span by thirty-five per cent. "We think our drugs vaporize a third of human diseases in the developed world." Pharma and biotech companies make money only if they treat a disease, and, because aging affects everything, the FDA doesn't recognize it as an "indication" susceptible to treatment (or to insurance-company reimbursement). So UNITY is taking aim at glaucoma, macular degeneration, and arthritis.

It has to be said that allotopic expression of mitochondrial genes in the cell nucleus is a poor example to pick for something that is alleged to be a doomed labor. The work has been accomplished for three of the thirteen genes needed; this is a capability that exists, and is underway towards completion. The allotopic expression of ND4 is the basis for a therapy that is currently going through clinical trials in Europe. Yes, it takes work, but so does everything else. This is one of the things that frustrates me immensely about many of the critics of SENS - they willfully ignore the progress that has been made, pretending it doesn't exist.

And that isn't even to start in on what is said - and, more importantly, not said - about senescent cell clearance, something that de Grey and other SENS advocates have been promoting as a path to treat aging for the past fifteen years, on the basis of strong evidence. It is right there in the SENS outline; hard to miss. Targeted removal of senescent cells has finally taken off these past few years, the evidence for a significant impact on aging has grown to be nigh irrefutable, and near everyone in the research community is enthused. Yet SENS and many researchers' past rejection of senescent cell clearance as a part of SENS is swept under the rug, never to be mentioned. It is unconscionable behavior, and it happens here: despite covering UNITY Biotechnology, the senolytics company, no mention of senescent cells is made in connection with the SENS vision. It takes some brass to claim SENS to be a doomed effort and then roll right into a discussion with one of the UNITY co-founders on the topic of removing senescent cells to treat aging.

Link: http://www.newyorker.com/magazine/2017/04/03/silicon-valleys-quest-to-live-forever

Comments

It is frustrating how little credit SENS gets - but I guess that is the penalty for being seen as something of an outlier - when I first started my research into this space I saw Aubrey as slightly nuts, and it took some more reading before I realized my mistake.

I fully expect the world to forget about SENS' involvement in allotropic expression of MtDNA or cross-link clearance etc, once those therapies gain widespread acceptance and are moving towards the clinic. In a way that will represent success: to be forgotten.

Posted by: Mark at March 28th, 2017 7:43 AM

A reasonable article though it does seem to mock Aubrey a little (note comment about stroking his beard which is irrelevant) and presents the mainstream and therefore reasonable approach as being the healthspanners. I take issue with Nir and others being the majority view and especially the silly loaded question he asked the audience, of course people will opt to die at 85 with such a question. We do however know that if you offer continued health the majority of people choose to keep living so its very childish to ask such a question knowing you are leading the aucidence.

On the whole not an awful article and I see it as generally good that this subject is appearing more often in mainstream media.

Posted by: Steve Hill at March 28th, 2017 8:58 AM

And yes, once again SENS get shortchanged and sidelined. This seems to be a very typical reaction in research and media, they all forget who funded senescent cell research in the first place!

Posted by: Steve Hill at March 28th, 2017 9:02 AM

Yeah that question at the end had me scratching my head... like what exactly was that supposed to prove?

Posted by: Anonymoose at March 28th, 2017 9:21 AM

I found the coverage on SENS to be decent by mainstream standards - and at least the journalist wrote several paragraphs about this approach to ageing, instead of just mentionning in passing or not mentionning it at all.
It also raised the scientific and personal/political issues that mainstream researchers have against Aubrey and SENS.

The reference to his beard didn't shock me at all ; it's merely a contextual information serving to garnish the story. And every story needs that, for those aren't dry factual scientific reports.

I'm also pleased to learn that Calico has been directly called out, as the following sentence shows : « "And he called me yesterday and said, 'I'm reading this book, "Homo Deus," and it says on page twenty-eight that I'm going to die.' I said, 'It says you, personally?' He said, 'Yes!' (In the book, the author, Yuval Noah Harari, discusses Google's anti-aging research, and writes that the company "probably won't solve death in time to make Google co-founders Larry Page and Sergey Brin immortal.") ».

Who knows. There's a very faint chance that this will eventually push Brin to hedge his bets and fund SENS. At least that's what a rational rich person would do.

It was disappointing that there were no retorts to the Immortal Dictator Ruling An Overpopulated Planet overused gag.

Posted by: Spede at March 28th, 2017 10:19 AM

The Google CEOs are businessmen, if SENS approaches them with a specific technology - for instance enzymatic degradation of keto-cholesterol - I think they might be more responsive. That's my feeling on the matter anyway.
They seem to be interested in acquiring IPs. That's how they've operated so far, I don't think their personalities will change overnight.

If Lysoclear is successful it might be useful as leverage.

Posted by: Anonymoose at March 28th, 2017 10:48 AM

I found the criticism of SENS on the basis that each item is hard, and so the probability of completing all of them in a reasonable time... a bit unreasonable. If six areas got partially solved, and people's lives were only shortened due to one class of damage, I imagine that a fair amount of extra funding would flow into it.

There is also a pervading cautiousness and lack of optimism. Can any of these areas, even cancer, really withstand scientific attack forever?

Posted by: Jim at March 28th, 2017 10:53 AM

"Amy Wagers, a researcher at Harvard, told me, "Part of the meaning of life is that we die." The Greeks warned about the danger of grasping for godlike powers. It didn't work out well for Asclepius or Achilles, and it worked out even worse for Tithonus, whose lover, Eos, begged Zeus to grant him eternal life but forgot to request eternal youth as well. Decrepit, senile, and miserable, Tithonus eventually shrank into a cicada who stridulated ceaselessly, calling out for release."

I'm sorry, but this type of comment might bother me more than the whole immortal dictator, or "everyone you love would be dead" arguments. Why is this such an accepted philosophy? I'm sorry, but I don't get it. I also don't get why people look at you like you're crazy when you don't agree that death gives life meaning. It's always nonsense reasoning that they use to back up the "death gives life meaning" nonsense, like the reference to Greek myths. Also, why does anyone get to tell else what gives their life meaning?

Nir's question at the end was nonsense as well. But If you're healthy every day for 85 years, there's no real reason you'd just drop dead one day. Or am I missing something?

I'm also kind of curious why they didn't have any kind of response for the immortal dictator nonsense, or how people shouldn't live forever because they'd be a drain on Social Security. This train of thought in regards to the consequences of longevity seems to be the norm though. Very rarely do you hear about any of the positives there might be. Given how people love to protest anything and everything nowadays, I wouldn't be surprised to see protests about any treatments that will extend your longevity (Well, anything that will have more meaningful results than say... Metformin?), let alone reverse aging... Or a treatment simply not released due to public outrage. Afterall, there would be many different areas to rail agains... resources, overpopulation, Social Security, Greek myths about Godlike power, and of course, it being unnatural. And given the way things are always presented towards the general public (like Nir's question at the end), it's easy to see why so many people aren't on the side of longevity. For now at least.

Posted by: Ham at March 28th, 2017 11:32 AM

If here in Europe rejuvenation treatments get prohibited, like GMO agriculture has been for 2 or 3 decades (and still is), I will certainly move somewhere, even as an illegal immigrant. It's my life what's at stake.

Posted by: Antonio at March 28th, 2017 2:23 PM

@Antonia, I agree. I don't think government should dictate our lives. I live in the U.S. and once the first treatment is available, I will wait a few years then do it. And, even if it involves medical tourism. FDA has it's place, but they are too restrictive and slow things down way too much, thus impeding progress.

Posted by: Robert at March 28th, 2017 3:05 PM

@Ham:

You wrote:

Given how people love to protest anything and everything nowadays, I wouldn't be surprised to see protests about any treatments that will extend your longevity

My comment:

I think its more likely that people will protests against high prices on life extension therapies and lack of access. So what every reasonable person should do is to secure s/he's own funds to use when that day arrive and you should also invest in these companies.

Posted by: Norse at March 28th, 2017 3:55 PM

Norse,

Well, I agree on the potential for price protests, but I was more coming at it from a religious, natural, or environmental aspect. Just look at any comments section on an aging article, pretty much anywhere.

But I agree with what you said about securing your own funds for if and when that day arrives. I've been doing that, already. We've been saving as much as we can anyway, but I haven't really had the talk about it with my wife yet, who would likely think I'm crazy, given our age, or how she isn't exactly interested in life sciences, amongst other things. But I digress... you were spot on.

Posted by: Ham at March 28th, 2017 4:43 PM

Hi there ! Just a 2 cents, I feel the same way, if rejuvenation therapies are an obscure (thing) most likely just like the age reversal telomerase therapy on Liz Parrish. And also a costly thing (at first), if I have to sort of go far to get it - I guess the investment will be worth it (life vs financial investment, basically your money = years of life..it's sad poor people will be left out as it will be unaccessible monetarily speaking and later maybe more affordable (doubt it), by then we will be some 30 years later (since it takes 10 long years just for One single therapy to enter the market/get approved by bodies FDA/HEalth Canada/Health Europe) if more and AdG will be in his 80s or gone.

''A few years ago, there was great excitement about telomeres, DNA buffers that protect the ends of chromosomes just as plastic tips protect
the ends of shoelaces. As we age, our telomeres become shorter, and, when these shields go, cells stop dividing. If we could extend the
telomeres, the thinking went, we might reverse aging. But it turns out that animals with long telomeres, such as lab mice, don't necessarily
have long lives - and that telomerase, the enzyme that promotes telomere growth, is also activated in the vast majority of cancer cells.''

Actually telomeres are already 'being lenghtened' inside our bodies (naturally) or mitigated in their speed of erosion - by telomerase (yes, even
in somatic cells who supposedly had no active telomerase, that's bs; they do have telomerase in minimal activity perhaps but still enough to
retard faster aging and sluggish cell cycling/cell cycle arrest/senescence). It was shown that telomerase acts, specifically, on the deadly smallest telomeres
in the lott and leaves the tallest ones alone. It makes sense. Telomerase is highly endocrine receptor, growth receptor (IGF/mTOR) and redox
dependent, meaning as we age our sexual hormones go down and that directly affects telomerase (for example testicular telomerase takes a dip as
men's testosterone levels dip around 60-70 years old); same for women, menopause (and in men, andropause) reduces oestrogen levels and that -
directly - affects telomerase levels (in fact telomerase works through 'estrogenic receptors' in the brain; it's also one reason why women live
longer then men, they maintain hormonal levels longer, thus have faster, quicker and longer access to telomerase activity inside their cells. On
top of the fact that men's testosterone is converted to estrogen in their bodies (as an extraneous step not helping) by aromatase - in order to
activate estrogenic receptor and thus, obtain telomerase, in men too). Growth hormones (which are released during sleep for tissue repair) by
pituitary gland have the same effect, they activate telomerase 'bursts'. Same thing for IGF. Hormones are directly tied to growth and the whole
'growth' problem of mTOR increasing cell size (which increase senescence); while CR retards 'body growth/cell growth' and impedes IGF, and impedes in telomerase
too; telomerase can be activated by CR only as the redox gets better otherwise overt CR may 'fragizile/frailty' a human.
This was shown with extreme starvation creating frailty and increased sudden death. If the redox is weaken being a certain point, telomerase
becomes totally unstable (and that's - where - it starts to behave 'Rogue' and cancer cells highjack it, it becomes a mutant form of hTERT that
increases cancer cell telomeres). The crux of it is that no matter telomerase is trying its best, in regular healthy aging, telomeres end up shortening anyway and more
and more small(er) telomeres accumulate in the lott of tall ones over the decades; until there are too many small telomeres among the tall ones - that can lead
to rapid extreme frailty and sudden death (seen plenty of times in studies in mice who developp tissue 'aging' very rapidly as massive tissue
senescence happens quickly (just like in progeria), they become frail, old-looking and die suddenly).

''But it turns out that animals with long telomeres, such as lab mice, don't necessarily
have long lives - and that telomerase, the enzyme that promotes telomere growth, is also activated in the vast majority of cancer cells.''

Yes these studies omit a big problem, these mice die of something else - like oncolytic senescence, not necessarily replicative senescene.
They prematurely die of cancer. And also, it was shown lately, that indeed the mice with shorter telomeres - died quicker and much faster
that mice who continuously kept - many more - taller ones (the mice's telomere were 'hurt' and had rapid loss, it doesn'T matter if you have
long telomeres - if you lose them extremely rapidly - they are gone quick and you die, just like mice even if they have high telomerase activity in their cells/genomic dysfunction is what happens in them; the trick with long animals, is that they Maitain the size of their
telomeres - for Much Much longer (thanks to the redox-telomerase interplay and with continous repair/genomic function maintenance). The mice who had sudden death had accumulated more 'small telomeres', indicating
fragilization/frailty. It seems number of small telomeres is a better indicator than length of telomeres, because it directly relates to the
'health' state condition (whether an animal is 'frail' or 'solid/healthy'; frail animals die prematurely). So we can not simply throw out these telomeres studies
they are important and show that indeed (even if there is much contention and muddied lines in them because they are not accurate like DNA methylation clock age marker),
damage is happening and animals that keep telomeres in - set 'frozen' size' - over very long periods
live the longest (that was proven in a 500 year old animal vs the - same - animal, that under environmental relocation, lives only 5-20 years; you read right, 500 years in the 'Correct' environment and dies in 20 in the 'Wrong' environment). Just, for example, a recent study demonstrated that birds who engaged in sex had quicker
telomere shortening in the very young years of their life and then, it seemed that sex had no more lasting effect in telomere rate of loss, just initially in the 'young bird formation years to become 'adult/puberty/reproductive capable' (telomerase/estrogen activate telomerase and improve sexual capability (I think it's a positive feedback mechanism to compensate for the damage/energy cost of reproduction), but sex remains
a energitically costly process for the body; producing sperm, eggs, sexual 'activity' (animals who are Truly overactive physically die younger from exhaustion creating overt damage),
telomerase can increase cortisol/adrenalin/epinephrin levels, or vice versa, depending on the situation/if stressed out or not (increase the fight or flight response (demonstrated with men who have a rise of testosterone when they 'win' a chess match, when they lose, their testerone
levels dip, This feeling of 'power' is directly linked to the 'Fight or Flight' mechanism; in that case you Fought (no fleeing) and You Won,
cortisol levels (change madly, which if they last too long there is high damage by cortisol levels lingering and creating a form of hypertension/accelerated aging just excessive stress 'stressed-out' (you ever read about people 'turning gray hair' 'overnight' from a stressful situation it'S not a lie, it's true and can happen) but it was shown that, overall, sexual activity is damaging because resource cost translocation change from DNA repair maintenance towards high sexual throughput (for example in high gravidity women whom had accumulated higher
mitochondrial lesions (8-oxodG) from multiple pregnancies vs no-kids women who had less mtlesions, showing that pregnancies (reproduction) were accelerating aging or at least, dysfuction in their mitochondrias (and obviously these high gravidity would of had sex)) and male animals who have the largest testicules (die the youngest) and procreate/get sex the most (, the 'alpha' male gets monopolizes 80% of sexual activity in many types of male animals, including humans - yet he will die quicker than beta males who are sexually amorphe (demonstrated (if not strongly) in historical euneuks who had their tesitucle balls removed and lived a bit longer than other men - if with possible frailty (since they might have reduced their IGF levels the instant they had them removed))). The whole sexual evolutionary theory at play).
In humans, IGF/mTOR is at the center of this, and as such sexual senescene is also a big problem that accelerates frailty (menopause and andropause, women dying of heart attacks after menopause - because of telomerase loss by estrogen loss, men become infertile - and a study showed that sexual senescence is a big problem in the salmon who becomes sexually senescent in 3 years, while if infected as a host to a parasite (parasite salmon) it goes on to live 13 years and sexually-active/non sexually senescent),again
this showing that the redox is behind all of this and damage must be kept in check otherwise sexual senescence happens; that leads to frailty and sudden death. People can actually live as infertile, many studies in animals showed an elongation of lifespan
with infertility (growth-hormone KO infertile mice and others), but they can suffer from frailty (that's not always the case though). In humans, hormones have a huge impact in our 'well being' and health. And thus, telomerase as important role in humans.

A recent study showed that C.elegans who lived the longest were infertile and spent the largest period in a state of 'lethargy/amorph' and
were truly 'frail'. And a recent study on impact aging, showed that female mice who lived - longer - then male mice - did - not - have an improvement
in 'health' condition. They were actually in a 'long-lived mutant C.elegans frail state', which is to say that health condidtion is important for lifespan
for there seems to be very 'permeable' interlinking between aging and health conditionl; that is to say that you can be unhealthy but young/not 'old' (replicatively senescent speaking),
while you can be old (chronologically) but healthy. It seems here, the longer lifespans = more frailty, not more 'health'; it's an error...
if you do keep your body (like an rejuvenation treatment that would remove all possible consequential damages) than yes it could be possible
to revert health state to good condition (that has been shown many times...but not with aging over decades), frailty increases mortality
but frailty - to a point 'just enough liveable' - can actually lead to a Longer Lifespan; I think it is analogical to 'pushing the engine a little further and making it exhaust some more';
that engine should have stopped died long ago - but somehow in its decrepit state - it keeps on 'rolling/turning' - it keeps on keeping'on with whatever's left in it.

Apply to a centenarian human (since they are the ones that matter in our case if just even want to live to a 100) and you realize that indeed humans, like Jeanne Calment, who lived to 122 were not 'perfect health' at a 122, they tons of
deficiecies and had 'make-due' with them and some people may not want that and prefer to die rather than continue living on for a long time
but in a 'half-assed/half-decrepit/half-liveable/half-dead bedridden' state. most people want perfect health (morbidity compression around 100 year old by longer lasting
'good healthspan') and then, die the next day in their sleep, no pain no decrepitude. I'm not sure if it's, truly, feasible even with SENS, really because an aged
body has accumulated much DNA damage, lesions, deletions as such it's like a rusted enging or a flower pot full of holes...that you try to 'Stich up',
water still empties a bit from the cracks even if you put a band-aid on (repairing damage should technically solve the cause of aging but
in humans it's more complicated than that, because some consequential pathways are non-damage related and cause aging too (like cell cycle arrest without any DNA damage response DDR for repair)
...(frailty of old age). Just a 2cent.

Posted by: CANanonymity at March 28th, 2017 4:59 PM

Yes that is true, healthspan and lifespan are not coupled absolutely. We know that already - centenarians definitely cannot be quantified as healthy, young, fit, etc. They are very old, very frail people. Living to 120 right now means living in a frail state for 40 years at the least. A long life with a long period of frailty. Not unlike those worms.

Achieving good health in old age on the other hand should also increase lifespan. Up to the point of your personal cancer barrier.

Ironically enough the so called healthspanners are actually chasing methods of lengthening the lifespan and not the healtspan. Insulin sensing and TOR are good and all but they produced long lived zombie like mutants in animal models and it seems to me this is the best way to ensure we get an epidemic of bed ridden 90 year olds on our hands rather than the peacefully dying 85 year olds Barzilai is advertising.

Posted by: Anonymoose at March 28th, 2017 6:32 PM

PS : some interesting bits from the article:

''...De Grey vexes many in the life-extension community, and one reason may be his intemperate life style. He told me, "I can drink as much as I like and it has no effect. I don't even need to exercise, I'm so well optimized." Until recently, he maintained two girlfriends and a wife. Now, he said, "I'm engaged, and my polyamorous days are behind me."

... D*mn .... AdG is burning/burnt the candles by both ends (see my sexual reprod comments above, ''Poly''-Alpha Male' A1).

''...Maris, who has retired from Google Ventures, strongly disagreed with that view. "This is not about Silicon Valley billionaires living forever off the blood of young people," he said. "It's about a 'Star Trek' future where no one dies of preventable diseases, where life is fair."''
That is a nice view (like that presented of AdG that SENS will be affordable) but truthfully I doubt it, it Will Remain a Silicon Valley Billionaire rich privilege thing for while then it will be more available. But in the end, poor people will Stay poor and die. It won't change (as) much as we think it with a 'Star Trek Future of Everyone Rejuvenated';
that could (still) be (too) far away and as such not available in our lifetime - because that is all that matters. Who cares if SENS happens in a 150 years' we'll be dead by then.

just like this comment :

''Matt Kaeberlein, a biogerontologist at the University of Washington, said, "It's like saying, 'All we have to do to travel to another solar system is these seven things: first, accelerate your rocket to three-quarters of the speed of light . . . ' "''

''The code book is far more complex for animals that excite our envy: the bee larva fed copiously on royal jelly that changes into an ageless queen; the Greenland shark that lives five hundred years and doesn't get cancer; even the humble quahog clam, the kind used for chowder, which holds the record at five hundred and seven.''

That is something to study deeply - the Greenland shark, living 100-400 years avg 250, it will confirm the results in other long lived animals like the 211-year old bowhead whales transcriptope study. I think I already know why it lives this long,
extremely slow growth/extremely protracted sexual maturity, the whole IGF-1/mTOR/telomerase/sexual hormones thing aging.

''As well as being a top predator itself, the Greenland shark has developed a defence against predators in the form of highly poisonous flesh. Not being hunted in its early years allows the shark to pursue a more relaxed reproductive strategy.
***Females don't reach reproductive maturity until an estimated age of 150 years.***''

Eye lens radiocarbon reveals centuries of longevity in the Greenland shark (Somniosus microcephalus)
''The age ranges of prebomb sharks (reported as midpoint and extent of the 95.4% probability range) revealed the age at sexual maturity to be at least 156 ± 22 years, and the largest animal (502 cm) to be 392 ± 120 years old. Our results show that the Greenland shark is the longest-lived vertebrate known, and they raise concerns about species conservation.''

Posted by: CANanonymity at March 28th, 2017 6:52 PM

Actually Antonio it's exactly your statistics that do not disprove what I said because health measurement is a subjective matter for the most part. In your static health in old age is simply a measure of not having a chronic disease (which in itself is a subjective measure) but that isn't any real measure of health.

You should look into papers on the well being of people above the age of 95 most of them cannot even dress themselves, half of them have severe mental defecits, all of them are physically frail and have trouble climbing stairs, a lot of them are blind, etc. And yet some of them reach extreme age. It is pretty clear to everyone with a bit of reading on the subject that in humans lifespan and healthspan are uncoupled - which is why the mainstream concentrates on healthspan - or at the least that is what they say.

How much healthspan and lifespan are uncoupled in humans is an open question. Obviously some measures of health are more important than others - you can reach 120 if you're blind and immobile - all you need to do is open your mouth to eat food, which at that point is typically liquid accounting for the inevitable lack of teeth of most centenarians.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830015/

A census of Portuguese centenarians and their disabilities. As you can see they are far from the image of good health. Obviously something is keeping them going but most of their organs are past the expiration date. In general it seems a somewhat functional brain is generally required but the rest of the nervous system could in various degrees of disrepair.

Posted by: Anonymoose at March 29th, 2017 5:33 AM

I think CANanonymity has a point - people (and other animals for that matter) clearly downregulate sex hormones and other growth signals as they get older - and this is probably protective (against cancer and other diseases of aging), even though it leaves them less robust and vital.

If this argument is right it means that less repair is needed to continue in such a state, but to continue at optimal (young) health requires a more vigilant repair system.

The case of the Greenland Shark demonstrates that slow development is consistent with a very long life. Birds on the other hand have a much faster metabolism but many species are also long lived - a consequence of much better mitochondrial health (lower ROS production, less permeable membranes, probably other measures too) than most mammals of an equivalent size and metabolism. So if you want to live fast you better have a good defense mechanisms against aging. Otherwise your best bet is to slow everything right down and life as a CR husk LOL! :)

Posted by: Mark at March 29th, 2017 5:46 AM

@Anonymoose:

"Actually Antonio it's exactly your statistics that do not disprove what I said because health measurement is a subjective matter"

If we assume that (that I don't), then your initial comment is unfounded.

"You should look into papers on the well being of people above the age of 95 most of them cannot even dress themselves, half of them have severe mental defecits, all of them are physically frail and have trouble climbing stairs, a lot of them are blind, etc."

If having a chronic disease is subjective, even more so for things like "cannot dress themselves" or "having severe mental deficits".

Posted by: Antonio at March 29th, 2017 6:12 AM

@Anonymoose:

"A census of Portuguese centenarians and their disabilities. As you can see they are far from the image of good health."

Again, that doesn't disprove the coupling but supports it. It shows that healthspan and lifespan are similar.

Posted by: Antonio at March 29th, 2017 6:20 AM

To disprove the coupling you would need the existence of many people that die at the current maximal or median lifespan of the whole population but that either:

(a) are healthy when they die (implying that lifespan is much shorter than healthspan)

or

(b) are sick/impaired/disabled when they die and well before that (say, in middle age) (implying that lifespan is much longer than healthspan)

Posted by: Antonio at March 29th, 2017 6:31 AM

When you show examples of frail people near the end of their lifespans, you are: (1) disproving (a) above (and thus partly proving the coupling) and (2) not proving (b) above (because you don't also show that they are frail well before dying).

Posted by: Antonio at March 29th, 2017 6:43 AM

I think what Anonymoose is driving at is that some of the process of aging is an adaptation to getting older, and this may result in greater longevity than would have been the case if the body was maintained at optimal health. I can think of many examples - reduction of stem cell activity to prevent cancer, reduction of sex hormones to down regulate MTOR, etc.

Posted by: Mark at March 29th, 2017 8:22 AM

The dialing down of the IIS pathway to reduce IGF-1 and GH and put the brakes on metabolism is another example Mark. The body reduces these levels just like what happens in CR too in an attempt to survive. Clearly explained in Hallmarks of Aging including the paradox:

"Paradoxically, GH and IGF-1 levels decline during normal aging, as well as in mouse models of premature aging (Schumacher et al., 2008). Thus, a decreased IIS is a common characteristic of both physiological and accelerated aging, whereas a constitutively decreased IIS extends longevity. These apparently contradictory observations can be accommodated under a unifying model by which IIS downmodulation reflects a defensive response aimed at minimizing cell growth and metabolism in the context of systemic damage (Garinis et al., 2008). According to this view, organisms with a constitutively decreased IIS can survive longer because they have lower rates of cell growth and metabolism and, hence, lower rates of cellular damage. Along the same lines, physiologically or pathologically aged organisms decrease IIS in an attempt to extend their lifespan. However, and this is a concept that will recur in the following sections, defensive responses against aging may have the risk of eventually becoming deleterious and aggravating aging. Thus, extremely low levels of IIS signaling are incompatible with life, as exemplified by mouse null mutations in the PI3K or AKT kinases that are embryonic lethal (Renner and Carnero, 2009). Also, there are cases of progeroid mice with very low levels of IGF-1, in which supplementation of IGF-1 can ameliorate premature aging (Mariño et al., 2010)."

http://www.cell.com/cell/fulltext/S0092-8674(13)00645-4

Posted by: Steve Hill at March 29th, 2017 12:56 PM

@CANanonymity no political party will be electable if they dont make access to rejuvenation central to ther manifesto

Posted by: scott emptage at January 9th, 2018 5:40 AM

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