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."
> 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.
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"
Even if this line is true, and I am not saying that it is, running and other cardiovascular activities lower your resting heart rate [1]. So even if you believe that you only have a finite number of heart beats, running should in fact increase your lifespan.
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.
Good question, but needs to be worked through more.
Consider an average person's 72/min resting heartbeat. That will be (726024365.25=) 37,869,120 heartbeats per year or ~379 million/decade.
Now, add strenuous running or cycling 5 hours/week, maybe a 10mi run, and a bunch of 20-60 minute runs. Call that average 180 beats/minute. That adds ((180-72)30052=) 1,684,800 beats/year, or +16 million per decade.
The average person's 37,869,120 beats/yr divided by the exercising person's 27,349,920 yields a ratio of 1.3846. So, based on heartbeat count alone, the exerciser will live 38% longer.
BUT, this kind of training will dramatically reduce the resting heartbeat. Training far less than this, my resting heartrate declined into the high-40s-low-50s, and has remained consistent for decades of mostly maintenance training. Most recent six month average is 52 beats/min. with far less than 5hr/week training, but let's use that. That means the resting heartrate is 27,349,920 beats/year, plus the added 1,684,800 exercise beats, making it 29,034,720 beats/year or ~290 million beats per decade.
That means the exercising person 'spends' 8,834,400 FEWER* heartbeats per year, or saves 89 million heartbeats per decade.
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.
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.
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.
Original article: "Cellular survivorship bias as a mechanistic driver of muscle stem cell aging" - 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."
> 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.
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"
Even if this line is true, and I am not saying that it is, running and other cardiovascular activities lower your resting heart rate [1]. So even if you believe that you only have a finite number of heart beats, running should in fact increase your lifespan.
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC6306777/
Unless you die on a trail run from a heart attack
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.
During the run their heart rate will be higher, but afterwards their resting rate might be lower.
Right, that was the question.
Is there a net benefit?
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.
Good question, but needs to be worked through more.
Consider an average person's 72/min resting heartbeat. That will be (726024365.25=) 37,869,120 heartbeats per year or ~379 million/decade.
Now, add strenuous running or cycling 5 hours/week, maybe a 10mi run, and a bunch of 20-60 minute runs. Call that average 180 beats/minute. That adds ((180-72)30052=) 1,684,800 beats/year, or +16 million per decade.
The average person's 37,869,120 beats/yr divided by the exercising person's 27,349,920 yields a ratio of 1.3846. So, based on heartbeat count alone, the exerciser will live 38% longer.
BUT, this kind of training will dramatically reduce the resting heartbeat. Training far less than this, my resting heartrate declined into the high-40s-low-50s, and has remained consistent for decades of mostly maintenance training. Most recent six month average is 52 beats/min. with far less than 5hr/week training, but let's use that. That means the resting heartrate is 27,349,920 beats/year, plus the added 1,684,800 exercise beats, making it 29,034,720 beats/year or ~290 million beats per decade.
That means the exercising person 'spends' 8,834,400 FEWER* heartbeats per year, or saves 89 million heartbeats per decade.
So Trump was onto something about conserving bodily energy?
https://www.cnn.com/2019/02/08/politics/donald-trump-exercis...
> 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.
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.
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.
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.
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