Frequently you make the claim about time frames and application to aging. While I do think that is something that needs to be looked at I also have a bit of a concern that it might include something of a error. An error along the lines of a fallacy of composition error—all the parts are small so the machine must be small.
In terms of senescence cells I’m not sure I follow you claim about they turn over too quickly. I understood the problem to be that some senescence cells don’t die but sit out there as zombies doing things that are generally not well coordinated with the rest of the system (our body). The cells that reach senescence and then are garbage collected for recycling are not a problem for us.
So as I understand the issue with senescence cells it is the slow accumulation of such cells relative to healthy, normally functioning cells that leads to the problem. That doesn’t seem to be a quickly turning over process. So when you say “senescent cells turn over too quickly” what is the context and what time frames are you considering?
This is exactly the model which the “Senescence-Induced Senescence” section is trying to test.
The data from here shows that the large majority of senescent cells do turn over quickly (~2-3 weeks), and this is true even in old age. The number of senescent cells which turn over quickly increases (slowly) with age, and the large majority of the age-related increase in senescent cell count is an increase in fast-turnover senescent cells. So there is definitely something increasing the production rate of senescent cells in old age. (That paper also estimates the age-related changes in both production and removal rates.)
Now, it’s still possible that accumulation of slow-turnover senescent cells could cause the increased production rate of fast-turnover senescent cells. That model has two key components:
There’s a subpopulation of senescent cells which do not turn over quickly, and accumulate over time
The presence of that increasing subpopulation is enough to cause the increase in fast-turnover senescent cells.
Quantitatively, the first component says there’s an increasing “base count” of slow-turnover cells, and the second component says there’s a multiplier. The same data used to estimate turnover can also be used to upper-bound the fraction of slow-turnover cells, and measurements of senescence-induced senescence should be usable to estimate the multiplier, so we should in principle be able to check whether the (small population of long-lived senescent cells + multiplier) theory is plausible.
Now, it’s still possible that accumulation of slow-turnover senescent cells could cause the increased production rate of fast-turnover senescent cells.
Reminds me of this paper, in which they replaced the blood of old rats with a neutral solution (not the blood of young rats), and found large rejuvinative effects. IIRC, they attributed it to knocking the old rats out of some sort of “senescent equilibrium”
Frequently you make the claim about time frames and application to aging. While I do think that is something that needs to be looked at I also have a bit of a concern that it might include something of a error. An error along the lines of a fallacy of composition error—all the parts are small so the machine must be small.
In terms of senescence cells I’m not sure I follow you claim about they turn over too quickly. I understood the problem to be that some senescence cells don’t die but sit out there as zombies doing things that are generally not well coordinated with the rest of the system (our body). The cells that reach senescence and then are garbage collected for recycling are not a problem for us.
So as I understand the issue with senescence cells it is the slow accumulation of such cells relative to healthy, normally functioning cells that leads to the problem. That doesn’t seem to be a quickly turning over process. So when you say “senescent cells turn over too quickly” what is the context and what time frames are you considering?
This is exactly the model which the “Senescence-Induced Senescence” section is trying to test.
The data from here shows that the large majority of senescent cells do turn over quickly (~2-3 weeks), and this is true even in old age. The number of senescent cells which turn over quickly increases (slowly) with age, and the large majority of the age-related increase in senescent cell count is an increase in fast-turnover senescent cells. So there is definitely something increasing the production rate of senescent cells in old age. (That paper also estimates the age-related changes in both production and removal rates.)
Now, it’s still possible that accumulation of slow-turnover senescent cells could cause the increased production rate of fast-turnover senescent cells. That model has two key components:
There’s a subpopulation of senescent cells which do not turn over quickly, and accumulate over time
The presence of that increasing subpopulation is enough to cause the increase in fast-turnover senescent cells.
Quantitatively, the first component says there’s an increasing “base count” of slow-turnover cells, and the second component says there’s a multiplier. The same data used to estimate turnover can also be used to upper-bound the fraction of slow-turnover cells, and measurements of senescence-induced senescence should be usable to estimate the multiplier, so we should in principle be able to check whether the (small population of long-lived senescent cells + multiplier) theory is plausible.
Make sense?
Reminds me of this paper, in which they replaced the blood of old rats with a neutral solution (not the blood of young rats), and found large rejuvinative effects. IIRC, they attributed it to knocking the old rats out of some sort of “senescent equilibrium”
The Conboys are looking to start human trials with they neutral blood replacement approach (https://newatlas.com/medical/diluted-blood-plasma-reverse-aging-in-mice/?utm_source=New+Atlas+Subscribers&utm_campaign=9db0c9efb9-EMAIL_CAMPAIGN_2020_06_16_01_29&utm_medium=email&utm_term=0_65b67362bd-9db0c9efb9-92444869).
I didn’t realize they were tying their work to senescent cells though.