Cells across the body talk to each other about aging
quantamagazine.org
quantamagazine.org
Scientists don’t yet know whether these findings apply to humans and how we age. Still, the hypothesis makes sense from a broader evolutionary standpoint, Dillin said. As long as the germ cells are healthy, they send pro-survival signals to ensure that their host organism survives to reproduce. But as the quality of the germ cells declines, there is no evolutionary reason to keep extending life span further; from evolution’s perspective, life exists to reproduce itself."
Curious what effect castration has on this mechanism.
When the individual's survival is the only selection factor, this is true - but it ceases to be the case in social species where reproductively non-viable individuals can still positively influence the reproductive chances of the young.
This may be an indirect feedback loop - but a little bit of latency doesn't make a huge difference when you're dealing with hundreds of thousands of generations of natural selection.
Otherwise phenomena like eusocial insects with sterile workers would not make sense. What is actually selected for, is genes that somehow promote more copies of themselves. This is the main takeaway from the book "the selfish gene".
However, the example of ants and bees shows that this doesn't exactly promote long lifespan in the sterile workers... Instead, they are mass-produced expendable drones.
However, it seems to me its more selecting for its own particular configuration of genes, that essentially select for a signature of themself.
Within a species the configuration between individuals is generally different enough to not ellicit altruistic behaviour.
In most animals, the 50% kinship gene relatedness threshold is definitely not enough to instigate self sacrificial behaviour. The children of a usocial species have to be like 11/16ths clones of eachother. And the runt suicide mechanism that triggers in rabbits requires a brood of true clones.
The reason I think it seems the genes select for individuals is because most circumstances will recquire that the current reproductive unit at the individual level needs to stay alive long enough for a net positive replication contribution to have been made.
when we reproduce, do we make copies of ourselves? no we don't. It's not survival of individuals. Read the Selfish Gene and it will change your thinking. You as an individual are a piece of clothing for your genes. Your genes reproduce, you don't.
It's more complicated than that. Your genes reproduce, but then that child is in your care, and you teach them your values. Then your values reproduce.
And then you're into nature vs. nurture. Your values can't reproduce if you have stupid genes that cause your offspring to die of cystic fibrosis, but your genes can't reproduce if you have stupid values that cause your offspring to be self-destructive and sterile.
"You" are the combination of your genes and your values, and whether there gets to be any more of that depends on whether you, as a whole, are any good at it.
That said, you are less likely to reproduce successfully if you are 'a social reject'.
You will meet fewer potential mates, fewer of those will be willing to reproduce with you, etc.
Whatever it was that made you a social reject, if it's something you can pass on either through nature or nuture, is less likely to be passed on.
source: Robert Sapolsky, Zebras Dont Get Ulcers
You have been blessed not to grow up with a narcissist or vicarious striver as a parent.
Technically, cars are a means of transportation for people. However, an honest assessment of the American transit system might lead one to believe that the safety and comfort of cars (or the automotive industry and ecosystem) are more important than the people they're supposed to ferry. In reality, the system is complex, incentives and drives are many; a holistic view is more useful than forcing a tortured atomic hierarchy onto that system.
I explicitly stated what i thought as contrary to the "survival of individuals".
Not only have I read the selfish gene, but I included 3 facts from the book in my comment...
These are often genetically identical with the rest of the hive, just on a different diet and with different treatment after the eggs are laid.
So what is selected for over any single cycle is sets of sets of genes conveying advantage.
Taking half of your genes from each parent could only select whole useful chromosomes from each parent (but is far better than nothing);
In order for genes to be selected in their own rights, you need more.
Chromosomal crossover copies genes across chromosome pairs - over the course of repeated iterations this allows useful mutations to be more easily distinguished.
Here is a counterexample where a gene or set of genes jumped ship and untethered itself from the individual they were originally embedded in:
A study of 81 historical eunuchs in Korea's royal court found a 14- to 19-year increase in lifespan compared to intact men of similar socioeconomic background; these eunuchs had a centenarian rate of over 3%.
https://en.wikipedia.org/wiki/Castration#Medical_consequence...
But it may reverse baldness? My guess is it may stop the progression but not reverse it, not regrow lost hair.
It probably can't be explained by loss of testosterone alone - since less than 1% of people live to be 100+.
It'd be good to know, though, what the lifespan of women in a similar environment would be.
Yet I wonder if those eunuchs had their testes removed, the WP article tells about removing the penis. If this is the case the eunuchs' testes were still there.
Uri Alon[1] argues thar it's the exponential growing chance of diseases/malfunctions as the amount of senescent cells surpasses certain thresholds.
Hah, thanks. I never made that connection.
The article's findings are also backed by data on Eunuchs who live almost 20 years longer than non-castrated men.
Now the real question is: Are Bryan Johnson and his followers willing to take logical next step?
The question is why this is the case... if it's historical data, it may simply be correlation, not causation, as in most societies eunuchs were prized and highly privileged compared to the general populations as the noblemen in power didn't see them as a threat to their biological line aka their wives (due to the obvious lack of balls and, in many cases, the penis). And no matter the era, those in privileged positions always enjoyed a longer lifespan due to the accessibility of consistent and higher-quality nutrition as well as healthcare.
The only thing coming close that we do have data for (simply out of ethical reasons) is pets and farm animals, and at least for pets there is some reduction in a few reproductive tract-related cancers (well, duh, what's taken out can't grow a cancer) [1] and higher life expectancy due to less fights.
[1] https://www.cats.org.uk/farnham/news/the-importance-of-neute...
Here's one of those papers: https://www.biorxiv.org/content/10.1101/2023.08.06.552148v1....
What has perplexed me is the notion of honest signals[1] in a world governed by natural selection and the survival of the fittest. Why wouldn't cheating exclusively emerge as the only strategy? Why wouldn't a species evolve a mechanism to survive longer and longer till it completely dominates?
Then it dawned on me that the survival of the species is not aligned with the survival of an individual. Cheating maximizes the benefit to that individual. But possibly damages the collective. Why is why honest signals even exist.
Aging and death as being pre-programmed is in service of the collective and that's why it even exists.
A bit of existential dread. But sharing it nonetheless.
There are proxies to genetic fitness that are frequently and successfully mimicked, though. See e.g.: https://en.wikipedia.org/wiki/Batesian_mimicry
Note what work and reproduced is only a minimum bar.
Because evolution happens faster with sexually reproducing generations that die out to leave room for the fitter youth.
Link to the Wikipedia article https://en.wikipedia.org/wiki/Peppered_moth_evolution
However, this doesnt explain tortoise (or 500 year old sharks)
The amount of energy required to sustain Human growth and Civilization just grows and grows. If we had a scalable balanced, fully renewable resource in everything, we likely would live longer.
I live near Yellowstone. There are seasonal hunting grounds the bison, which live a decade or two, won’t cross into. The wolves, meanwhile, don’t live long enough for the lesson to stick. So they continuously cross and get shot.
Humans erected an invisible barrier. The bison adapted where the wolves, arguably the more intelligent creature, did not, in part due to the latter’s short lifespan.
The best of both worlds would be a long-lived polygamous creature that’s constantly reproducing. Ecology, however, proscribes limits on that approach.
The selfish genes control, and their survival is not perfectly aligned with either the individual or the species. If aging becomes too slow, adaptation slows, and successful genes become more rare and their propagation slows. Genes are replicators, replicators need turn-over to replicate, and greater age means slower turn-over.
It may be that the advent of cultural replicators have decreased the optimal turn-over rate of genetic replicators, but they don't know that.
So that's an available trade-off. Increase individual age limits, but maintain adaptation rates by letting many immature individuals compete and die before maturity. Like spermatozoa and tadpoles.
That's what I meant by "if there were group selection it might, as the older people displace resources for the younger."
There's an equilibrium of honesty and dishonesty. If everyone is dishonest, no one trusts, and the dishonesty doesn't pay off. If everyone is honest, everyone trusts, and dishonesty pays off all the more.
[1]: https://en.wikipedia.org/wiki/Group_selection#Criticism
It would seem like a species that has a language would greatly benefit from having individuals with more years of experience on how to handle infrequent events like droughts, floods, abnormal animal migrations, etc.
I also think that we are hardwired not to be able to believe our own lies, because of this. There is (99.9% of the time) a tell, for humans. For someone to effectively lie to us, we need to want to believe the lie, otherwise it fails.
The TV show "Lie to me" is therefore a fascinating exploration (a bit exaggerated in its effectiveness) of how to detect and point out such tells.
https://ncase.me/trust/ is well worth playing to get an idea of how this works.
(Also, by way of acknowledging that reality is more complex than simulations like the Prisoner's Dilemma, in reality you might also have options like "stop interacting with defectors in order to avoid lose-lose situations" or "warn others about defectors, and listen to others' warnings but weight them based on whether the entity giving the warning is honest". And conversely, defectors get more options like "pretend to be a different entity with no history" or "pretend to be a known trusted entity".)
There is no cheating, since we could not modify our genomes and give ourselves superpowers. We cannot live forever because there was no need. We won’t die before we can successfully reproduce.
that reads like you missed the last 10 years of genomics and the Nobel prizes for Jennifer Doudna and Emmanuelle Charpentier, among other proven DNA/RNA manipulations.
your point could turn out true, since edits to genomes AND superpowers resulting is what you said wouldn't work. maybe the second half of the conjunctive clause isn't possible, but we don't know yet.
i guess the future will be interesting!
This assumes, incorrectly, that each generation of children are birthed into a new separate pocket-universe, where absolutely nothing prior generations do next--including suddenly dying--can ever affect their own trajectories.
Consider genes Alpha and Beta, where Alpha kills women right after menopause, and the Beta lets them live ably to 120. Do you really think there's no difference between the trajectories of clan Alpha and clan Beta?
Or perhaps a Cronus gene [0] which increases fitness and lifespan but causes paranoid infanticide. Just because a gene-copy was made doesn't mean the gene stops mattering.
First you declared genes had no evolutionary pressure on longevity after children existed... but now you're amending it to grand-children existing?
Well, what about great-grandchildren? How many more times must you be forced to move the goalposts before realizing that the logic behind them is simply wrong?
You can't just ignore stuff like kin-selection, which we've known about for over a hundred years already.
If the offspring requires parenting, the parent, once an offspring, also required parenting and so on.
This is not moving the goalpost, it’s doing the similar things adapted in some ways for the environment every generation.
I assumed you were talking about humans. For salmon, the definition of a successful reproductive cycle is simply reproducing. For humans, it takes longer and requires parenting. But genes don’t get selected away when it’s passed on to the next generation.
> "There is no more evolutionary pressure on lifespan after you have children"
is an inaccurate oversimplification.
In drought years these backups may end up getting the herd through the worst of it.
And it turns out that for elephants, water availability is one of the biggest limitations on reproduction. Provide a population with an artificial water source and it will explode in short order.
Interesting thought. So if we simply force people to reprocreate later in life, we'll select for genes that allow for that, possibly also bringing longer lifespans in general (to protect the early offspring.)
I wonder if education, and cultural protection of teenagers has already done that to some extent.
In short, the path to immortality is to hold off children longer and longer... Hypothetically.
The unit of survival is not the individual or the species, but the gene. Genes maximize their survival by combining via sexual reproduction with other genes over time. Any one combination of genes will be out-competed over time.
The reason for honest aging signals is that a gene survives longer by getting out of the way of its offspring's combinations with other, newer genes. Sexual reproduction is the only way to get access to new phenotype features.
It's not service for the collective. Hanging around in one individual is the genetic version of vendor lock-in.
which are an expression of the concept of gene over the field of informatics, instead of the field of biology (unit cells vs unit bits)
All models are wrong but this one is mine, IANA biologist, yadda yadda.
- there are only so many resources to sustain individuals
- ergo there's a cap of the number of individuals
- ergo some individuals will die, if not from age, from attrition
- if age is not factored in, there are more old individuals, genetic competition between young individuals is reduced as they have to compete for resources with old individuals
- ergo age which kills old individuals irrespective of available resources allows more young individuals to exist in such a pool
- ergo ageing a) promotes competition between young individuals b) increases mixing of the gene pool
- ergo it promotes quicker turnaround on mutations
- ergo ageing is a significant asset in species adaptability to change
IOW vendor lock-in sucks in face of changing conditions as one is suddenly stuck with a suboptimal solution and competitors have a harder time emerging to challenge the status quo.
conversely the benefits of short term ageing are counterbalanced by social effects, where elders, even when not reproductive anymore but still otherwise in good health and thus autonomous as well as minimally consuming resources, are able to provide support for their chain of descendants, freeing energy for parents-to-be to reproduce, then parents to gather more resources that are then directed to support their younglings. The lack of reproductiveness of elders is advantageous to the species as it removes them from the direct gene mixing pool, instead promoting the younger ones.
IOW for its individual lives to be longer, a species goes increasingly social, channeling more support and thus energy towards their younger members, but ageing is still key otherwise the species ability to face quick change (at evolutionary scales) is severely hampered.
The deeper question for me is whether ageing is a specific primary process (a literal clock, which a technique such as the paper would attempt to skew backwards) that emerged from evolution or if it is a secondary effect from entropy corrupting other processes (e.g there's constant degradation + a ton of error correction but at some point degradation is too high and error correction cannot cope, triggering a catastrophic cascading effect leading to the sudden inability for an organism to sustain its own life, which the paper would delay by introducing younger cells, thus less errors, thus error correction can cope for longer)
- after you reproduce evolutionary pressures have way less leverage and are limited to how an individual effects the copies of their genes that still might reproduce
- excess longevity will result in an older nonreproducing individual competing with copies of its genes leading to evolutionary pressure to die when below a threshold of usefulness to younger generations of your genes
I don’t see why aging can’t be reversible, I’ve heard some people say it’s an impossible task because they equate aging with the fact that time can only move forward and therefore aging must inherit the same property. But aging is just damage that accumulates over time, but damage can be repaired with the right tools.
I should say I am not a biologist, I just try to use my imagination to solve problems and this what it’s telling me about aging.
Aging is loss of information, you can't reverse that. You can prevent it though.
We have a whole lot of redundancy and mechanisms to restore/repair redundancy. But even so, there's a march of entropy upwards; oxidation, genetic damage, cell death, tissue damage, neuron loss, etc.
We don't have repair mechanisms for everything the body knows how to build, and the repair mechanisms that we do have become less effective to use (and often less safe) as the body ages.
That is another way of saying loss of information and increase of entropy.
We don't understand aging well enough to say this with any confidence.
Very different from saying “aging is loss of information.”
It’s interesting to think about the implications of such a technology, if we can swap DNA with another, fresher copy, we should also be able to modify it and make the body do things it wasn’t previously capable of doing. One idea that comes to mind is expanding the range of our senses, or giving our body a better system to repair and regenerate itself beyond what we naturally evolved to able to do so we can have longer life spans with a quality of life that makes it worth it.
It sounds like a bad idea to play god like this, and it probably is, but we’ll never know until we give it a serious try. I remember a while ago a scientist in China modified the DNA of human embryos by using Crispr, the goal was to make them resistant to HIV infection and he was jailed and ridiculed for it.
The search space for new and improved capabilities is endless once we learn how to program DNA like a computer. We are probably at least a century away from this level of control, and probably another century before it becomes socially acceptable to do it at scale.
But even they have the predation damage. https://en.m.wikipedia.org/wiki/Blue_whale
No, that's outdated. Another theory that aging is an intentional, programmed process is gaining more and more traction lately. Damage does accumulate over time, but it's not because the cells are incapable of repairing it, it's because they deliberately don't want to repair it. The developmental program that starts with conception just turns self-destructive at some point. We "only" need to reset its state to such that corresponds to a younger age.
Cognitive Scientist Claims Evolution Is Not The Full Story https://www.youtube.com/watch?v=FriefeHhp5E
Even, uncontacted sentinel island tribes still behave very much like a human.
I asked ChatGPT ...
"the rough estimate for the data storage capacity of the human genome in bytes is approximately 6 billion bits .... or equivalently, 750 megabytes."
That doesn't seem like its enough.
"The storage capacity of DNA is typically expressed in bits or bytes, as DNA can be used as a medium for data storage. Each base pair can represent 2 bits of data (since there are four possible combinations: AT, TA, CG, GC). Therefore, the human genome, with 3 billion base pairs, can theoretically store about 6 billion bits of data.
To convert this into bytes, you divide the number of bits by 8 (since 8 bits make up 1 byte). So, the rough estimate for the data storage capacity of the human genome in bytes is approximately 6
billion bits 8 = 750
million bytes 8 6billion bits
=750million bytes, or equivalently, 750 megabytes."
I'm glad that the article did say this, though: "Scientists don’t yet know whether these findings apply to humans and how we age."
https://www.nad.com/news/harvard-professor-david-sinclairs-i...
Why is it always like this? Even "in mice" I think they always start with an animal that has been genetically modified to age faster or show some trait of aging and then cure that, as opposed to taking a normal healthy mouse and extending its age by 40%, no?
Because it is an easy way to write a paper?
Even with the genetic line, same chow and environment, it's possible to have mice that are ill in one location and healthy in another.
https://www.alzforum.org/news/research-news/gut-microbes-dif...
The article is written in such a way that you think it is about human cells until you get fairly far into it.
With that said, this research is about how cells cooperate to form a multicellular animal.
I think it would be interesting to use the results to design an experiment that could be applied to animals more closely related to humans (that with these results in hand you could get passed the animal ethics committee).