aging is largely the consequence of cellular mechanisms that evolved to reduce or prevent cancer.
In this case, any animal that undergoes a statistically successful anti-aging intervention should ultimately die from cancer. At least, that would be expected for most of them. What about the rest of the animal kingdom? What about C. elegans?
Aging is evolutionary conseved => Molecular mechanism is evolutionary conseved. Any aging theory should propose a molecular mechanism of aging that can "kill" yeast, worm and any mammal.
And this is not about "damage" for sure.
Yes, any mammal would ultimately die from cancer, because you can't excape the genomic instability that causes cancer.
But there is no evidence or reason to believe that the molecular mechanisms of aging are the same for all species, or the same for yeast, worms and mammals. Why would one think that? Can yeast get cardiovascular disease? Does yeast get cancer?
"...there is no evidence or reason to believe that the molecular mechanisms of aging are the same for all species"
Yes, there is.
If a drug acts similar on a biological function in evolutinary distant spicies, then this biological function has a conserved molecular mechism. E.g. inhibition of respiration (Complex iV) with cyanide. Actually, iInhibition of any metabolic pathway with known drug.
If
Rapamycin and /or calories restriction extend lifespan (Aging) in all eukaryotes. (True statement)
then
Rapamycin and/or calories restriction effect on evolutionary conseved molecular mechanism.
Aging has evolutionary conseved molecular mechanism and this mechanism is identical in all eukaryotes.
"Can yeast get cardiovascular disease? Does yeast get cancer?"
Aging is a graduale decline of the biological functions = adaptive traits.
Different spicies have different adaptive traits.
Yeast cell loose its own adaptive traits during aging; Fly is loosing completely different functions = adaptive traits; Mammals are loosing they own adaptive functions;
But, any biological unit age, and because above mention statements on rapamycin/calorie restriction = True, the molecular mechanism must be evolutionary conserved or even identical.
There is insufficient evidence that rapamycin or CR extends lifespan in all species, or even in healthy animals. There is plenty of evidence that what these two interventions do in mammals is just prevent the detrimental overfeeding and excessive nutrient signaling. As demonstrated in detail in the manuscript and previously here:
https://doi.org/10.1016/j.mad.2021.111584
Furthermore, all organisms undergoing calorie restriction or consuming rapamycin still age, so they do nothing to explain how we age.
It is also not true that any biological unit ages. Bacteria, hydra, cancer cells and the germline are all immortal, as are most unicellular organisms. Why are they immortal, but we are not? My explanation for this is cancer (risk), but I'd like to hear a better one.
I think that the idea has a correct core: there is a balance between rejuvenation and prevention of cancer in organisms. Eg telomer's limit. However, if evolution needs to suppress cancer without affecting life expectancy, it can do it but tweeking many anticancer defence mechanisms. Examples are whales and elephants. (Ineterstingly, crocodiles never have cancer - and aging - as they grow all life and die on starvation.)
Whales and elephants are far bigger than humans, so they have experienced more evolutionary pressure to suppress cancer, producing better solutions for that. Evolution is not a conscious process that can do things "it needs", solutions have to be found by random mutation, and then fixed.
And for the claim that crocodiles never get cancer, do you have any evidence? That would be an outstanding achievement for a vertebrate. Such claims are usually nonsense.
I agree with what you say i. the first paragraph. I saw the claim about crocodiles here https://www.mdpi.com/2073-4409/15/9/749
The first sentence in the abstract says "Crocodilians rarely develop cancer", which means they do. So that is perfectly reasonable. Crocodiles can get very old, no doubt, and their species maximum lifespan might be much longer than currently known. So their anticancer mechanisms might be interesting, like those of whales or elephants, but this confirms rather than contradicts the tumor suppression theory of aging.
Let's imagine, that we age for the Tumor Suppression reasons. Why didn't we develop a mechanism of reducing tumors, in the same way as bowhead whales or the naked mole rats?
Their existence suggests that the regeneration-cancer trade-off is not fixed. Moreover, transferring naked mole-rat Has2 into mice improved cancer resistance and extended lifespan. Why should comparable improvements in humans be considered futile rather than difficult but tractable engineering problems?
So, even if it can be the way to organise some of the hallmarks of aging, it means that there's some pressure, that prevents developing the mechanisms to prevent it.
Whales are far bigger than humans, so they have experienced more evolutionary pressure to suppress cancer, producing better solutions for that. Naked mole rats get cancer, despite being quite small.
I wouldn't say better tumor suppression mechanisms are completely futile. But I would say it is quite difficult, and there are easier solutions than trying to insert new functions into the germline without knowing how to do it. Maybe someone should transfer naked mole-rat Has2 into monkeys and see what happens.
One could also say making humans grow a set of wings on their back so that they can fly shouldn't be considered futile, but a difficult but tractable engineering problem. So should we try? Flying would be cool, or? And it's just a little engineering.
Personally, I try to make suggestions that are likely to work, and work well. Thinking about what might happen if we transfer genes from other species into humans is fine as a though experiment or for science fiction writers.
But I don't think this is helpful if one wants to do something against having to die.
Historically, evolutionary biology has explained the evolution of aging as the consequence of a mortality-driven decline in selection pressure at older age, meaning that aging is a product of neglect, not intent. Aging is then produced either by a genetic trade-offs between early-life fitness and late-life mortality (known as antagonistic pleiotropy), or as the consequence of restrained investment into somatic maintenance, causing molecular damage to accumulate over time (known as the disposable soma). None of these theories identify which genes or which kind of damage is important and actually causes aging.
The Tumor Suppression Theory of Aging (TSTA) proposes that aging proposes that in mammals, aging is largely the consequence of cellular mechanisms that evolved to reduce or prevent cancer. I show that most hallmarks of aging suppress tumorigenesis, and how they can be rearranged into a causal hierarchy instead of an arbitrary flat list. Furthermore, the hallmarks of aging are interconnected not by accident or due to evolutionary neglect, but because they interact synergistically to remove cells deemed to proliferate abnormally. A cell cannot magically detect oncogenic mutations, so evolution relied on the proxy signal of accelerated proliferation and associated metabolic and replicative stress to identify potentially dangerous cells exiting dormancy, and limit their proliferative potential. This leads to stem cell exhaustion as how mammals age and remaining cellular capacity as the primary store of biological age. Aging is not the consequence of evolutionary neglect or an artifact of domestication, but an unavoidable consequence of the instability of DNA producing oncogenic somatic mutations and the need to contain the cancer risk arising in animals with long lifespans and large body sizes.
The idea that tumor suppression mechanisms might cause aging originated decades ago, but was abandoned largely because caloric restriction (CR), drugs thought to slow aging and interventions into conserved aging pathways delay both aging and cancer, contradicting the idea. By explaining how CR slows aging via reducing proliferation rates, the tumor suppression theory of aging resolves this conundrum and identifies the instability of DNA giving rise to cancer as the ultimate reason why we age and the dominant factor constraining the evolution of very long, if not indefinite, lifespans in larger animals.
Because aging is not a consequence of evolutionary neglect, but it has been optimised by evolution, the TSTA suggests that trying to treat aging with drugs is a futile effort, similar to trying to treat stupidity with drugs. Healthy people don’t need drugs. There are no drugs that make us smarter, healthier or more resistant to disease. In the same way, there are no drugs that make us age slower. Except for drugs that cause us to eat less. Such drugs make us age slower relative to a control group that eats too much, which rodents do almost inevitably, because nutrient signalling accelerates proliferation, and therefore aging.
The TSTA also suggests that blaming aging on evolutionary neglect, i.e. that aging hasn’t been under effective selection, creates a universal excuse for shoddy theories of aging. Aging theories that blame aging on things that would be easily fixable, but suggest they aren’t fixed due to insufficient selection pressure, should be rejected as not making sense.
I would be particularly interested in opinions or arguments trying to prove this wrong. Several weaknesses are explained in the paper, available here:
https://www.researchgate.net/publication/403538169_How_Somatic_Mutations_cause_Aging_without_Causing_Aging
A previous version is available from SSRN, but please use the above Researchgate version, which contains several minor improvements. If possible, please try to read it first. Sorry, it isn’t short. Feel free to skip over the molecular details parts that might be excessively detailed.