I don't agree with your definition of aging.
"this is what happens when we age” No, it occurs throughout our llifespan
“So given that senescent cells result from aging” As above, this is not true; it happens because cells age, not the host.
We age throughout life, not just when we are old. The point being made - let me put it you another way - senescent cells increase with time, because cell divisions increase with time - when cells stop dividing they either go senescent or to apoptosis. As time progresses - which happens to coincide with aging (which we hope to change) - we have more and more divisions and so accumulate more and more senescent cells, which are tricky to get rid of.
It seems you to suppose that it is just ascredible that young people have more senescent cells than older people, than the other way round. Even if we don't know and we do know that they accumulate with age - we can look at tissues - it would be an absurd suggestion with no biological logic. What possible mechanism would explain it? That more cells have died in younger people than old? That cell apoptosis is biologically easier older than when young?
When stating that not all senescent cells are resist apoptosis, there is the implicit implication of another reason - autophagy, which worsens as we age. Hence the build up of damage - your reason seems to be predicated on time working in reverse.
No there isn't an alternative to them not accumulating, just as I stated. The assertion is made in the presence of apoptosis - this is like contradicting that aging, the build up of damage, isn't inevitable becaue we have autophagy. It is happened to every human that has lived to be old - they all have accumulated damage - whether they have died of the damage or not and they all have had cells which perform autophagy. Senescent cells accumulate, we don't get rid of them all. When we're old we're still clearing up damage but we're accumulating more than we can cope with - hence the build up.
It is no longer inevitable because we have interventions and may be able to trigger apoptosis through senolytics. This is a different matter.
Now, there is a quote directly from a paper than senescent cells accumulate with age, that the are found at increased levels found in a range of age related pathologies - you want to disagree well ok.. What you seem to be resisting is that tissue samples taken from old people aren't indicators that they accumulate with age. Why would you think that?
Yes of course the Biran quote is correct, limit our understanding, does not mean we dismiss our current knowledge, obviously. There are observations we can and have made which do not require us to witness in vivo.
"So what we need – and seems to be lacking, which is a shame, but hopefully someone’s on it, as without it nothing else can be done – is a biometric of total senescent burden."
This makes no sense to me. If you have the number - then what, do you know what it means? How many do you need to get rid of? Who knows. Plenty can be done without knowing the exact amount - and I, others and a few mice can bear witness to that.
If we're old we have damage, and part of that damage are senescent cells, lifestyle choices will make a difference, we may be worse or better off relative to our peers but to suggest we might not have any damage because it hasn't been measured in whole?
I can only make out that you believe you may not have any senescent cells because nebulous lifestyle choices may have irradicated them all. Well, no lifestyle choices have kept anyone alive indefinitely.
Nobody here has perfect information. You have to draw reasonable conclusions on the information avaialble and make a decision. Interventions on mice are good and we are all getting older. There is nothing left for me to pursue here - I am not going to a lab and take samples and provide slides. No lifestyle choice is going to make us or our cells 50 years younger.
Edited by ambivalent, 31 January 2023 - 07:48 PM.
