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We can't currently cure aging and there is little convincing evidence that suggests we will be able to anytime soon. This is despite the claims of many attempts at peddling false hopes by folks like David Sinclair and Aubrey de Grey. We can mitigate some downsides of aging at best. Aging is baked into our genes as natural selection never had a reason to favor any other approach.


How do you suppose that is? If a species were completely able to avoid the effects of aging (including age-related diseases and degeneration) what evolutionary reason would there be for death at such an early age. Especially in the case of mammals, the process of rearing the young is a large investment of resources which takes a long time to produce a return. Surely it would be better to minimize that expenditure and have members of your species who've had time to learn from their experiences. If population were to become a problem, there are already plenty of instances of species killing their own for various reasons so some form of population control doesn't seem to be an entirely unexpected adaption. Sure there may have been other things that were more prescient at the time such as disease, lack of food, etc. But I don't see why not aging would be evolutionarilly unfavourable?

I'd split things into 3 cases: (1) aging is something for which there is a strong evolutionary pressure, (2) aging was dominated by other factors and is more or less indpendent of evolution, and (3) aging is something that is strongly unfavourable in evolution. In case (1), it may be that there are strong genetic mechanisms for evolution which we cannot reverse without changing genetic data. In case (3), we have to ask the question of why we age, given evolution has worked against it. If there were some compound that could prevent aging significantly, why don't more of us naturally produce it. Case (2) is where I'd expect the problem to be the most attainable. The existence of certain compounds that seem to alleviate aging significantly might be interpreted as evidence against the third case. If such (often naturally ocurring) compounds exist, then why don't we produce them? Of course, more evidence would be necessary to say anything conclusive.


Brenner touches in this in a recent paper:

https://www.sciencedirect.com/science/article/pii/S016749432...

> Second, animal gene sets evolved to allow individuals to acquire food, avoid predation, find mates and successfully reproduce. Long-lived species like humans also provide a substantial investment in caretaking of offspring until they can obtain food, avoid predation and reproduce for themselves. The advantages conferred to youth by parents mean that genetic selections for parental health are extant in caretaking species. Such genetic selections for post-reproductive health are not extant in non-caretaking species (Brenner, 2022a).

...

> Think of it this way: if foxes can reproduce at 6 months, what genetic selections are present for them to live for six years? The ones that live for 6 years might reasonably produce 6 times as many offspring as those who perish in a year but those who die in a year would still contribute to the gene pool so long as they are successful at reproducing. Indeed, experiments done in flies that were selected for the ability to reproduce late in life suggest that hundreds or thousands of genes, not single dominantly acting genes, are modified to allow every organ system to function better over time in the resulting long-lived flies (Burke et al., 2010). However, animals in the wild are under little to no direct genetic selection for longevity beyond that to produce reproductive success.

Personally, my guess is that long lifespans are a tradeoff with reproductive age fitness. Also, it seems there are diminishing returns for longer lifespans and the benefits of knowledge transfer from post-reproductive age individuals.


Brenner claims "Animal gene sets have been subject to genetic selections for guile, strength and famine-resistance but have not been directly selected for longevity because". This is case 2 in my classification.

He writes, "Indeed, experiments done in flies that were selected for the ability to reproduce late in life suggest that hundreds or thousands of genes, not single dominantly acting genes, are modified to allow every organ system to function better over time in the resulting long-lived flies (Burke et al., 2010)." The case of sirtuin genes, however, is disctintly different from this. The hypothesis there is that increased expression of sirtuins increases longevity. This is a change to the epigenome, not to the genetic content itself, which is what is what Brenner comments on.

Also, what this says is not that "evolution never had any reason to favour another approach", but that evolution (at least in this controlled environment) was not able to stop aging. Perhaps you have other data to support that claim. Also, what this says is not that "evolution never had any reason to favour another approach", but that evolution (at least in this controlled environment) was not able to stop aging. Perhaps you have other data to support that claim.

From the perspective of maximizing reproduction, maximizing fertile population is oviously ideal. Surely, if it's possible for a member of the species that is fertile to continue to reproduce and live longer, this would increase the species' overall reproductive capacity. Obviously, post-reproductive age individuals do not have this benefit. However, it doesn't seem improbable that loss of reproductive ability is caused by aging.

I think that the tradeoff you mention between reproductive age fitness would make sense in the context of other adversity though. If survival in general is very difficult, surviving long enough to reproduce, reproducing as fast as possible, and being able to survive long enough to finish the process while it's placing various stressors on your body is desirable.


Are you basing this on research you've seen that runs counter to the unbridled optimism of Sinclair and others, or is this belief of yours just a consequence of your belief about "natural selection never had a reason to favor any other approach"? I'm just wondering for myself, as an outsider to all this, what reason I would have to take your view rather than theirs.


Charles Brenner has been fairly active in debunking many of Sinclair's claims:

https://www.sciencedirect.com/science/article/pii/S016749432...

Brenner also had a debate with de Grey:

https://youtu.be/MJIvp_J-kzM

I was initially put off by Brenner because he can be abrasive but as far as I can tell he is correct and unrelenting when it comes to pointing out bad science.


This is probably the key flaw with TFA. It makes the claim in the headline, and then doesn't back it up at all. Not a single reference or fact to justify this rather staggering assertion.


What makes you think that the aging process is somehow fundamentally irreversible?


yes. current medical science is having issues treating simple thing with humans (paralysis or any thing related to it ). solving aging, may be in next 500 years.


Solving aging isn't the sum of all other cures.

It could be just another track of medicine we haven't really begun to formalize correctly


"Humans overestimate progress in the short term and over estimate it in the long term."

You're discounting the law of accelerated returns. It might take another 50 years to make a "big discovery/milestone in curing aging" but from that point forward it might become a lot easier to cure aging.


... and gene therapy is now a reality.




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