4 ms·

Aging muscle stem cells shift from rapid repair to long-term survival

84 points by bikenaga 9mo ago

bikenaga 9mo ago
Original article: "Cellular survivorship bias as a mechanistic driver of muscle stem cell aging" - https://www.science.org/doi/10.1126/science.ads9175 https://www.science.org/doi/10.1126/science.ads9175 Abstract: "Aging is characterized by a decline in the ability of tissue repair and regeneration after injury. In skeletal muscle, this decline is largely driven by impaired function of muscle stem cells (MuSCs) to efficiently contribute to muscle regeneration. We uncovered a cause of this aging-associated dysfunction: a cellular survivorship bias that prioritizes stem cell persistence at the expense of functionality. With age, MuSCs increased expression of a tumor suppressor, N-myc down-regulated gene 1 (NDRG1), which, by suppressing the mammalian target of rapamycin (mTOR) pathway, increased their long-term survival potential but at the cost of their ability to promptly activate and contribute to muscle regeneration. This delayed muscle regeneration with age may result from a trade-off that favors long-term stem cell survival over immediate regenerative capacity."
- Qem 9mo ago
  > We uncovered a cause of this aging-associated dysfunction: a cellular survivorship bias that prioritizes stem cell persistence at the expense of functionality. Past forty, pitiless new equations take hold. Sacrifices must be made... https://www.badspacecomics.com/post/the-suit https://www.badspacecomics.com/post/the-suit
TacticalCoder 9mo ago
> Aging muscles heal more slowly after injury—a frustrating reality familiar to many older adults. > In skeletal muscle, this decline is largely driven by impaired function of muscle stem cells (MuSCs) I take it that as mitosis (cell division) gets slower with age, there's also simply no way aging muscles could potentially not heal more slowly? So slower mitosis and then in addition to that muscle cells going into a "less repair, more survival" mode. Darn, sucks to get old.
- lumost 9mo ago
  No known mechanism, but cross species checks would imply that the schedule was evolved and has some control mechanism. Species that evolved before the Devonian period tend not to age and instead grow through their entire lives. There is no mechanistic understanding for the wild variation in species lifespans. So the natural question in these studies is what would happen if we simply told the muscles not to age this way. It’s plausible that this aging schedule evolved due to other factors independent of the biological constraints. It’s also plausible that evolution removed some other important components for longer lived stem cells.
  - nanomonkey 9mo ago
    Interesting, the Devonian also appears to be the period at which fish started sporting limb like appendages and muscle structures, and other animals started to explore land. Perhaps unlimited body growth doesn't work well for animals not entirely supported by water.
    - Nevermark 9mo ago
      Interestingly, the limbless boa constrictor's growth slows, but never stops.
  - Nevermark 9mo ago
    I misread that as the "Denisovan period" and found it interesting that in addition to Homo Floresiensis Hobbits, there might have been arbitrarily large Denisova Hominin giants. Oh well. I will have to be satisfied with Andre the Giant.
mugivarra69 9mo ago
[dead]
readthenotes1 9mo ago
This makes me wonder if that line "I only got so many heart beats, I'm not going to waste them running" has some validity -- I thought Satchel Paige said it, but apparently not. He did say "I generally don’t like running. I believe in training by rising gently up and down from the bench. " Which also fits the "don't prematurely age the stem cells"
- deleted 9mo ago
  [deleted]
- EGreg 9mo ago
  So Trump was onto something about conserving bodily energy? https://www.cnn.com/2019/02/08/politics/donald-trump-exercise-health-physical https://www.cnn.com/2019/02/08/politics/donald-trump-exercis...
- vostok 9mo ago
  Do you know if running causes a person to have more or less heartbeats in a given time span? I'm not particularly medically knowledgeable and not sure.
  - normie3000 9mo ago
    During the run their heart rate will be higher, but afterwards their resting rate might be lower.
    - antisthenes 9mo ago
      Right, that was the question. Is there a net benefit?
      - import 9mo ago
        There is a net benefit. Your heart gets stronger and spends less effort for pumping out the blood. Your resting HR becomes lower and blood has more oxygen. And this happens 24/7. Assuming you’re running 5K 2 times in a week.
m3047 9mo ago
There's some rather woo woo stuff out there about an evolutionarily conserved mechanism for intercellular signaling as a danger response which involves the mitochondria shifting their metabolism to help cells repel invaders, but which also interferes with the cells' normal activity. TLDR: if there's chronic inflammation cells go into this mode but never get the "all clear". Could this be the qi? Pun intended. It's just anecdata, haven't spent any time looking into it per se. Stumbled onto this because I've been using TCM (in consultation with an herbalist) for blood pressure, relatively successfully, for a couple of years. Of course they didn't have blood pressure cuffs in the Ming or Han dynasties, so we're not really treating blood pressure... Researching astragalus and di huang is what led me to it.
r0ze-at-hn 9mo ago
> Benjamin, compared muscle stem cells isolated from young and old mice and discovered that a protein called NDRG1 increased dramatically with age—reaching levels 3.5 times higher in old cells than in young cells. So ERa down-regulates NDRG1 and there is less ERa activation when we age. Evolution is all fun, but before reaching for anything like that we can apply basic knowledge around that path. We can pick a random gene downstream of ERa to get a grant and write a paper on how it is different in people that are older. Years of possible papers to write.
rajnathani 9mo ago
Interesting point: > The research suggests that increased NDRG1 expression emerges through what the scientists call a "cellular survivorship bias"—stem cells that don't accumulate enough NDRG1 die off over time, leaving behind a population of slower but more resilient cells.

84 points by bikenaga 9mo ago

Original article: "Cellular survivorship bias as a mechanistic driver of muscle stem cell aging" - https://www.science.org/doi/10.1126/science.ads9175 https://www.science.org/doi/10.1126/science.ads9175 Abstract: "Aging is characterized by a decline in the ability of tissue repair and regeneration after injury. In skeletal muscle, this decline is largely driven by impaired function of muscle stem cells (MuSCs) to efficiently contribute to muscle regeneration. We uncovered a cause of this aging-associated dysfunction: a cellular survivorship bias that prioritizes stem cell persistence at the expense of functionality. With age, MuSCs increased expression of a tumor suppressor, N-myc down-regulated gene 1 (NDRG1), which, by suppressing the mammalian target of rapamycin (mTOR) pathway, increased their long-term survival potential but at the cost of their ability to promptly activate and contribute to muscle regeneration. This delayed muscle regeneration with age may result from a trade-off that favors long-term stem cell survival over immediate regenerative capacity."

Qem 9mo ago
> We uncovered a cause of this aging-associated dysfunction: a cellular survivorship bias that prioritizes stem cell persistence at the expense of functionality. Past forty, pitiless new equations take hold. Sacrifices must be made... https://www.badspacecomics.com/post/the-suit https://www.badspacecomics.com/post/the-suit

TacticalCoder 9mo ago

> Aging muscles heal more slowly after injury—a frustrating reality familiar to many older adults. > In skeletal muscle, this decline is largely driven by impaired function of muscle stem cells (MuSCs) I take it that as mitosis (cell division) gets slower with age, there's also simply no way aging muscles could potentially not heal more slowly? So slower mitosis and then in addition to that muscle cells going into a "less repair, more survival" mode. Darn, sucks to get old.

lumost 9mo ago
No known mechanism, but cross species checks would imply that the schedule was evolved and has some control mechanism. Species that evolved before the Devonian period tend not to age and instead grow through their entire lives. There is no mechanistic understanding for the wild variation in species lifespans. So the natural question in these studies is what would happen if we simply told the muscles not to age this way. It’s plausible that this aging schedule evolved due to other factors independent of the biological constraints. It’s also plausible that evolution removed some other important components for longer lived stem cells.
- nanomonkey 9mo ago
  Interesting, the Devonian also appears to be the period at which fish started sporting limb like appendages and muscle structures, and other animals started to explore land. Perhaps unlimited body growth doesn't work well for animals not entirely supported by water.
  - Nevermark 9mo ago
    Interestingly, the limbless boa constrictor's growth slows, but never stops.
- Nevermark 9mo ago
  I misread that as the "Denisovan period" and found it interesting that in addition to Homo Floresiensis Hobbits, there might have been arbitrarily large Denisova Hominin giants. Oh well. I will have to be satisfied with Andre the Giant.

mugivarra69 9mo ago

[dead]

readthenotes1 9mo ago

This makes me wonder if that line "I only got so many heart beats, I'm not going to waste them running" has some validity -- I thought Satchel Paige said it, but apparently not. He did say "I generally don’t like running. I believe in training by rising gently up and down from the bench. " Which also fits the "don't prematurely age the stem cells"

deleted 9mo ago
[deleted]
EGreg 9mo ago
So Trump was onto something about conserving bodily energy? https://www.cnn.com/2019/02/08/politics/donald-trump-exercise-health-physical https://www.cnn.com/2019/02/08/politics/donald-trump-exercis...
vostok 9mo ago
Do you know if running causes a person to have more or less heartbeats in a given time span? I'm not particularly medically knowledgeable and not sure.
- normie3000 9mo ago
  During the run their heart rate will be higher, but afterwards their resting rate might be lower.
  - antisthenes 9mo ago
    Right, that was the question. Is there a net benefit?
    - import 9mo ago
      There is a net benefit. Your heart gets stronger and spends less effort for pumping out the blood. Your resting HR becomes lower and blood has more oxygen. And this happens 24/7. Assuming you’re running 5K 2 times in a week.

m3047 9mo ago

There's some rather woo woo stuff out there about an evolutionarily conserved mechanism for intercellular signaling as a danger response which involves the mitochondria shifting their metabolism to help cells repel invaders, but which also interferes with the cells' normal activity. TLDR: if there's chronic inflammation cells go into this mode but never get the "all clear". Could this be the qi? Pun intended. It's just anecdata, haven't spent any time looking into it per se. Stumbled onto this because I've been using TCM (in consultation with an herbalist) for blood pressure, relatively successfully, for a couple of years. Of course they didn't have blood pressure cuffs in the Ming or Han dynasties, so we're not really treating blood pressure... Researching astragalus and di huang is what led me to it.

r0ze-at-hn 9mo ago

> Benjamin, compared muscle stem cells isolated from young and old mice and discovered that a protein called NDRG1 increased dramatically with age—reaching levels 3.5 times higher in old cells than in young cells. So ERa down-regulates NDRG1 and there is less ERa activation when we age. Evolution is all fun, but before reaching for anything like that we can apply basic knowledge around that path. We can pick a random gene downstream of ERa to get a grant and write a paper on how it is different in people that are older. Years of possible papers to write.

rajnathani 9mo ago

Interesting point: > The research suggests that increased NDRG1 expression emerges through what the scientists call a "cellular survivorship bias"—stem cells that don't accumulate enough NDRG1 die off over time, leaving behind a population of slower but more resilient cells.