8 ms·

Rejuvenating the blood cell population

88 points by etiam 3y ago

sieste 3y ago
"in mice", goddammit!
robwwilliams 3y ago
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.)
- fartsucker69 3y ago
  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.
  - flobosg 3y ago
    “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.
- valuegram 3y ago
  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.
  - flobosg 3y ago
    The Wikipedia article lists some criticisms about the hypothesis: https://en.wikipedia.org/wiki/Grandmother_hypothesis#Criticisms_and_alternative_hypotheses https://en.wikipedia.org/wiki/Grandmother_hypothesis#Critici...
- throw310822 3y ago
  > 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.
  - thriftwy 3y ago
    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.
    - b112 3y ago
      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.
      - SilHunter 3y ago
        [flagged]
      - thriftwy 3y ago
        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.
        b112 3y ago
        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.
- flobosg 3y ago
  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.
  - bigbillheck 3y ago
    > ...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.
  - pazimzadeh 3y ago
    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/ https://pubmed.ncbi.nlm.nih.gov/25517375/ A cold-blooded view of adaptive immunity https://pubmed.ncbi.nlm.nih.gov/29556016/ https://pubmed.ncbi.nlm.nih.gov/29556016/
    - flobosg 3y ago
      > 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/journal.pbio.1001120 https://journals.plos.org/plosbiology/article?id=10.1371/jou...
- mlyle 3y ago
  > 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.
  - Traubenfuchs 3y ago
    > long lifespan ...isn't it just better healthcare and nutrition?
    - gumby 3y ago
      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.
    - Retric 3y ago
      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.
    - rbanffy 3y ago
      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.
m3kw9 3y ago
“ You can be sure that someone is going to try to do it, too” Follow Bryan Johnson for updates
- ImHereToVote 3y ago
  Hell. I would do it. If I had the scratch.
chasil 3y ago
Does this relate to the shutdown of the thymus (the "murder university")? The thymus goes dormant at the age of 85,as I've read. The lymphoid strain can specialize into t-cells, which is the speciality of the thymus. https://m.youtube.com/watch?v=LmpuerlbJu0 https://m.youtube.com/watch?v=LmpuerlbJu0 The myeloid does provide macrophages, but they are of little value compared to an activated b-cell on a mission.

88 points by etiam 3y ago

"in mice", goddammit!

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.)

fartsucker69 3y ago
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.
- flobosg 3y ago
  “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.
valuegram 3y ago
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.
- flobosg 3y ago
  The Wikipedia article lists some criticisms about the hypothesis: https://en.wikipedia.org/wiki/Grandmother_hypothesis#Criticisms_and_alternative_hypotheses https://en.wikipedia.org/wiki/Grandmother_hypothesis#Critici...
throw310822 3y ago
> 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.
- thriftwy 3y ago
  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.
  - b112 3y ago
    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.
    - SilHunter 3y ago
      [flagged]
    - thriftwy 3y ago
      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.
      - b112 3y ago
        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.
flobosg 3y ago
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.
- bigbillheck 3y ago
  > ...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.
- pazimzadeh 3y ago
  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/ https://pubmed.ncbi.nlm.nih.gov/25517375/ A cold-blooded view of adaptive immunity https://pubmed.ncbi.nlm.nih.gov/29556016/ https://pubmed.ncbi.nlm.nih.gov/29556016/
  - flobosg 3y ago
    > 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/journal.pbio.1001120 https://journals.plos.org/plosbiology/article?id=10.1371/jou...
mlyle 3y ago
> 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.
- Traubenfuchs 3y ago
  > long lifespan ...isn't it just better healthcare and nutrition?
  - gumby 3y ago
    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.
  - Retric 3y ago
    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.
  - rbanffy 3y ago
    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.

m3kw9 3y ago

“ You can be sure that someone is going to try to do it, too” Follow Bryan Johnson for updates

ImHereToVote 3y ago
Hell. I would do it. If I had the scratch.

chasil 3y ago

Does this relate to the shutdown of the thymus (the "murder university")? The thymus goes dormant at the age of 85,as I've read. The lymphoid strain can specialize into t-cells, which is the speciality of the thymus. https://m.youtube.com/watch?v=LmpuerlbJu0 https://m.youtube.com/watch?v=LmpuerlbJu0 The myeloid does provide macrophages, but they are of little value compared to an activated b-cell on a mission.