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Comment by pdm55 | Hacker News Reader

I have never believed the argument that we can develop a way to live to 200. I am now in my mid 60s and it seems that a number of my parts are starting to "wear out". My skin is certainly thinner; my eyesight is damaged (macula degeneration) in one eye; ... And covid has taught us that our immune systems are not as effective as when we were younger. We older folks all see heart and cancer problems over the horizon. Cancer just seems a matter of time: I mean how can our cells keep replicating the 3 billion(?) base pairs in our genomes - with a mistake rate of about 1 per 100 000 (i.e. 30k mistakes per division) - without those eventually leading to cancer? And if I could only remember how to spell that alzyhmr thing, I would mention it also. And why does our government keep sending me those kits for faeces samples? Sorry to disagree with you, but I don't think aging is a reversible process: we seem to have too many parts, each with an "expiry date".

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The main reason why it seems like it's not just a matter of "parts wearing out" is that different animals all age at different rates, but strikingly they all seem to age in similar ways.

For example while dogs have a much shorter lifespan than humans they seem to face all the same age-related declines humans face. This holds for animals close to or exceeding our mass as well. If different parts of the body wore out simply due to e.g. mechanical stress, you would expect e.g. dog joints to be perfectly healthy after 15 years since they are biologically very similar to human joints, when in fact dogs tend to still have arthritic and otherwise fragile joints at 15 (or earlier).

Everything declining together, just on different timetables in different animals, seems to suggest that aging is controlled by either a single mechanism or some interwoven set of mechanisms that cause everything to fail at the same time, rather than individual parts failing because "they wear out." If you could target that mechanism(s) then maybe you can make humans live as long as e.g. tortoises. But of course we haven't confirmed that such things exist, but the above is at least some motivation for why they might exist.

I would guess it is because there was no evolutionary pressure to have joints that can sustain 80 years if there are other parts of body that only sustain 18. Maybe I am missing something but I would expect that life expectancy of various parts of body of each specie converge because of that.

Evolution is rarely so tidy in its convergence. Humans have vestigial organs and crazy anatomical features left over from our ancestors. In light of that it would be a rather stunning coincidence to find that when it comes to aging across species (!) that organisms seem to have all their systems age at the same rate simply by individual evolution of each of those systems or that all the systems are effectively immortal with nothing in-between.

Without a coherent theory of senescence this is all conjecture, but there's compelling evidence that there's some set of hidden variables we aren't seeing that is "pulling the strings" when it comes to aging.

What compelling evidence?

On reflection evidence is too strong a word given that we don't have a good, specific hypothesis for what's going on. Observations of the sort I laid out above.

Not a biologist, but I'm following related research and at this point am fairly convinced that aging is an intentional, pre-programmed process, as opposed to the popular understanding that it's the consequence of wear and tear.

Let's just think logically about it for a bit. Your cells come with all kinds of repair machinery and redundant DNA encoding. All cells do. But there are single-celled creatures that don't age and reproduce by cell division, and they haven't lost their function despite billions of years and millions of generations. Same for humans and whoever else reproduces sexually — there's A LOT that needs to go just right for a new human to be born, including making billions of copies of parents' DNA, yet it does work just fine most of the time. This tells us that the DNA copying process must be very robust, and that with age, it's these mechanisms that keep everything in check that deliberately get weaker or stop working altogether.

Recent research proves it.

For example, there's evidence that organisms propagate their age throughout all tissues using some kind of signaling in the bloodstream: https://www.nature.com/articles/ncomms13363

Even more bizarre, the aging clock, as determined by DNA methylation, gets reset to zero at the beginning of embryonal development: https://hplus.club/blog/how-and-when-mother-nature-resets-th...

You're not wrong, but your models of aging events seem to be too simplistic. Aging is not one process but a complex of interacting processes.

There are definitely a number of processes involved in aging that are pre-programmed as you suggest, namely the hormonal clocks involved in puberty and maturation, and then later senescence.

It's not particularly useful to compare humans/mammals to single-celled organisms, which operate under way fewer constraints. They don't have to deal with cancer, as just one very basic example. They also don't have to figure out how to clear old junk from their tissues and individual cells. They just start over with a clean slate every time.

Signals in the bloodstream - various hormones and immune cells - are obviously involved in aging. But there are many of them, and we are just starting to understand their different interactions. There is no doubt that aging research is going to yield ways to suppress or promote the action of certain hormones, replenish/reactivate certain stem cell populations, etc. but better understanding of intercellular regulatory networks is needed for that.

To call DNA methylation the determinant of an "aging clock" is also too narrow or simplistic. DNA methylation is the mechanism of cell differentiation, but it's "metadata" that has to be copied over between cells when they divide, just like the DNA itself. Early in embryogenesis, the DNA methylation pattern is reset and overwritten using the regulatory cascade of master control genes (homeobox, etc.) - so it is expected that the methylation pattern will have lower fidelity with each division cycle before or after that point.

This is the golden age of biology - we have just gotten a hold of the tools that will let us solve these problems - but it's messy and complicated. Investing in your understanding of these processes can have a huge payoff - I recommend reading some of the Nature Reviews articles like https://www.nature.com/nrg/ - I've always found them to be incredibly helpful in summarizing the state of the art.

Every cell in your entire body (on average) gets replaced over a 7 year span. If you figure that you stopped growing around 18, and your body has been slowly replicating itself since then, it completed the first full replication at 25, the second at 32, the third at 39, the fourth at 46, etc. Each time you accumulate some chaos. As the chaos grows, the cell groups decline in performance. The decline in performance makes it more likely that the next replication will be even worse.

While that makes it really unlikely that aging can be reversed, it certainly isn’t logically impossible. All you need to do is expell the chaos, and get one good quality regeneration (possibly taking about 7 years) and then you’d be right back to 18 years old again. That might make it worthwhile enough to be willing to have your body burned by a billion laser shots and float in a vat of liquid for 7 years. We might get to find out in our lifetimes? who knows.

Good movie on the subject https://www.imdb.com/title/tt8548830/

Not a biologist, but certain sharks, whales and tortoises have been known to live for >150 years, so I suppose it is theoretically possible.

Greenland shark reach sexual maturity at 150 years, and can live for over 400 years according to Wikipedia.

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