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Comment by robwwilliams | Hacker News Reader

Original paper just published in Nature. This commentary helpful. But not sure I understand this statement:

“…the rebalancing towards the innate immune system with aging is very likely an evolutionary adaptation to keep up acute responses with age while relying more on B-cell memory for the adaptive immune system to handle variations of the usual pathogens.”

Selective pressure does not operate after the reproductive phase of life. There is little or no “evolutionary adaptation” to cope with degradation of function with aging.

(The so-called grandmother effect is still a weak hypothesis.)

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> Selective pressure does not operate after the reproductive phase of life.

Even if we don't know the exact mechanism, it seems like we have evolved a longer lifespan in a safe environment than any other ape, while our lifespan in the wild was probably comparable to many apes.

Whether this long lifespan after reproductive age was selected for directly (e.g. grandmother hypothesis or patriarchal effect), or whether it happened because of some other evolutionary accident, it seems to be real.

Lowe points out here that there's a rebalancing of blood composition that happens later in life that would likely have been beneficial in the past, which is (very weak) evidence for a selective pressure that increased post-reproductive lifespans.

> long lifespan

...isn't it just better healthcare and nutrition?

No, that increases the survival rate, but it's been documented for thousands of years at least that the "natural" human lifespan is over 70.

Mean lifespan has been dragged down mainly because of high rates of infant mortality and, as you allude to, various untreatable diseases. But as we make progress on those, the mean has been shifting up.

2,000 years significantly fewer people reached 90+ as a percentage of the population, but it still happened.

We have done quite a lot in terms of infant mortality, but relatively little to extend the maximum age people reach. Take 1,000 random people born 100 BC vs 1,000 people born in 1900 and the oldest person from 1900 will very likely have lived longer but probably less than 10 years longer.

Living longer can be advantageous as you can take care of your children and grandchildren for longer, as well as continue to amass resources after the reproductive age, but indirectly improving the chances of your descendants.

Like the gay uncle hypothesis. (-;

It's easy to forget in modern society, but in tribal society the elders were fountains of wisdom. When computers, reference materials, technical documents, libraries, school systems, etc don't exist, the value of lived experience goes through the roof.

Being able to consult the elders when the group faces perplexing problems (who may have lived through something similar, or at least heard stories from the recently deceased generations who have) might mean the difference between between 20% of the population starving and no one starving.

This is all true but these indirect effects are generally too weak to actually modify allele frequencies in humans. These so-called grandmother effects were probably more forceful in the hunter-gatherer phase of human evolution—but even then may have been weak.

Yes!

Mice in the wild have a lifespan of roughly 365 days. Divide by ten to get life expectancy for humans “in the wild”. Mice living in a sheltered vivarium (but with pathogen exposure) make it out to 600 to 700 days. Mice in a specific-pathogen free vivarium routinely get to 700 to 900 days. Divide by ten again to get life expectancy of humans in a supportive “healthy” environment with some medical support.

From this point of view, mice live roughly 2.5X their reproductive lifespan; very similar to human post-reproductive lifespan.

There is nothing unusual or special about human lifespan, or even maximal longevity. Some normal mice (not growth hormone mutants) make it out to 1400 days.

The heritability of life expectancy increases with age in both mice and humans. Or crudely put—bad luck kills you in youth; bad alleles kill you in old age.

That claim seemingly stems from a misinterpretation of the paper’s discussion, since no mechanisms are proposed or mentioned there:

> The evolution of the vertebrate immune system occurred in geographically limited populations. Before machine-mediated transportation— trains, planes, boats and cars—individuals were likely to be exposed to the majority of pathogens in their local geography by the time of reproductive age. As T and B memory/stem cells can survive an individual’s lifetime[60,61], they should be sufficient to provide adaptive immune memory to all local pathogens. Thus, the generation of new T and B lymphocytes in later life was probably no longer advantageous, whereas the production of short-lived myeloid cells would remain important for acute innate responses, even in later life.

I'm not sure I understand what biogeography has to do with their point which seems to mainly be about the passage of time.

Also, I thought the adaptive immune system came about in marine vertebrates? Doesn't water mix things up pretty well?

Re-evaluation of the immunological Big Bang

https://pubmed.ncbi.nlm.nih.gov/25517375/

A cold-blooded view of adaptive immunity

https://pubmed.ncbi.nlm.nih.gov/29556016/

> I'm not sure I understand what biogeography has to do with their point which seems to mainly be about the passage of time.

Individuals in different biogeographical niches can have distinct “passages of time” in their immune systems, depending on their exposure to endemic pathogens.

> Doesn't water mix things up pretty well?

So does air, but you don’t see a homogeneous distribution of airborne pathogens around the world :)

By the way, thanks for those papers, they reminded me of single-domain antibodies (or “nanobodies”), which appear to have evolved independently in cartilaginous fish and camelids: https://journals.plos.org/plosbiology/article?id=10.1371/jou...

> ...vertebrate...Before machine-mediated transportation— trains, planes, boats and cars—individuals were likely to be exposed to the majority of pathogens in their local geography by the time of reproductive age

This hypothesis would be testable by looking at migrating animals, such as gray whales or arctic terns.

What's weak about the grandmother effect? Selective pressure absolutely applies outside of reproductive phases of the individual. Evolution happens at the genetic level, not only at the level of the individual organism. If a related organism is able to increase the reproductive chances of another organism with shared DNA (i.e. a child, grandchild, sibling, etc.), the related organism won't be directly reproducing, but it will absolutely be affecting the genetic material being passed down.

The Wikipedia article lists some criticisms about the hypothesis: https://en.wikipedia.org/wiki/Grandmother_hypothesis#Critici...

> Selective pressure does not operate after the reproductive phase of life.... The so-called grandmother effect is still a weak hypothesis.

If so, then it's really hard to explain how female humans manage to live 40 years past their reproductive age.

There's much less wear and tear on our bodies, now that we have roofs and HVACs and clothing and cars to move us around. That's how we live till 80 instead of 50. That plus nobody trying to hunt and eat us.

Animals also live significantly longer in zoos.

Human lifesoan hasn't changed, only average age of death has. (You may be alluding to this)

Average age of death has gone up, due to asprin, antubiitics, vaccines, improved hygene, and so on.

I don't buy the wear and tear side of thibgs, and zoo animals, pets have vaccines, health care, medicine, and checkups too.

Wear and tear is the key, especially in the regions with winter. You don't want ot be without walls and heating during winter.

In warm regions, perhaps HVAC / having at least rudimentary shade is equally important.

People have had walls and heating during winter, wood or coal for heat, going back 1000s of years.

And houses for shelter just as long.

Unless you think people lived without houses in the 1800s, and heat, it's modern medicine that's changed, dramatically, the outcome here.

Ans there are plenty of moderate climates that had no better life expectancy than colder ones.

We didn't see much evolution of Homo Sapiens in the last 1000s of years.

We had a lot of shaping by selection of existing traits but not that much long term evolution. We're essentially "running on the same hardware" as these pre-house Homo Sapiens.

What allowed prehistorical Homo Sapiens to live for 50 years now lets us do so for 80.

Leaving aside modern evolutionary theory, your assertion about the same hardware agrees with my position.

You need to look at life expectancy rates for the last 200 years. The big change is in the 1900s.

Not when we first built warm, heated houses, thousands of years ago.

I agree with you, though I believe that live expectancy was very uneven back then.

You want either modern medicine and sanitation, or low population density. The latter is very hard to combine with low wear and tear. So it's really both medicine and comfort.

> Animals also live significantly longer in zoos.

Humans and many apes probably had similar lifespans in the wild, but humans have this huge post-reproductive lifespan in safe environments that other apes don't.

You can turn that on the head and say human females have really short reproductive span.

Human males don't, though. They're often reproductively capable at 60.

Yah, that's the possible patriarchal effect mentioned elsewhere. But it's unclear how much that actually happened "in the wild."

A car doesn't break down immediately after you maintain it.

no idea where you got the idea for that nonsense. there is a ton of selective pressure after reproduction. there are really an uncountable number of mechanics affecting survival fitness of each individual in a group after reproduction.

“Survival” and “fitness” of an individual are two separate concepts. The latter is directly related to the amount of potential offspring (and thus reproduction), the former is not.

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