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”
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.