A private message (from someone who may name themselves if they wish) asked about the claim that “the effects of senolytics rapidly wear off once the drug stops being administered”.
This is a lower-confidence claim than most in this piece; I do not have a study on hand directly proving it. The vast majority of papers on senolytics either use regular administration (frequency ~1 per 2 weeks or faster) or do a short regimen and then measure results within ~2 weeks; the ubiquity of those practices is itself a significant piece of evidence here. If a single dose does nothing long-term, then I mostly expect to see very few papers published using a single dose on long-term outcomes (because people don’t publish negative results), and that is indeed what I see.
Of course, lots of people still claim that long-lived senescent cells are a thing, but it’s always either uncited or cites someone else who also has no actual data directly supporting the claim. I have yet to see any compelling data backing it up, and this is a case where I expect absence of evidence to be evidence of absence. It feels very similar to the claims about amyloid beta as a cause of Alzheimers, or collagen:elastin ratio as a cause of vascular stiffening: lots of people claim it, but following the citation chains shows no compelling evidence.
What I’d really like to see is an experiment which gives one (or a few) doses of a senolytic to reasonably-old mice (maybe ~20 mo), measures outcomes ~ 1 week later, then waits at least a couple months before evaluating outcomes again. If persistent senescent cells are both real and relevant, then we’d expect to see relatively little regression in outcomes over time. If persistent senescent cells are not real or not relevant, then we’d expect to see the mice mostly regress to the pre-treatment state after a couple months. (Though they would probably be slightly better off than control mice, since they’d have effectively taken a couple weeks with the core aging feedback loop on pause.)
A private message (from someone who may name themselves if they wish) asked about the claim that “the effects of senolytics rapidly wear off once the drug stops being administered”.
This is a lower-confidence claim than most in this piece; I do not have a study on hand directly proving it. The vast majority of papers on senolytics either use regular administration (frequency ~1 per 2 weeks or faster) or do a short regimen and then measure results within ~2 weeks; the ubiquity of those practices is itself a significant piece of evidence here. If a single dose does nothing long-term, then I mostly expect to see very few papers published using a single dose on long-term outcomes (because people don’t publish negative results), and that is indeed what I see.
Of course, lots of people still claim that long-lived senescent cells are a thing, but it’s always either uncited or cites someone else who also has no actual data directly supporting the claim. I have yet to see any compelling data backing it up, and this is a case where I expect absence of evidence to be evidence of absence. It feels very similar to the claims about amyloid beta as a cause of Alzheimers, or collagen:elastin ratio as a cause of vascular stiffening: lots of people claim it, but following the citation chains shows no compelling evidence.
What I’d really like to see is an experiment which gives one (or a few) doses of a senolytic to reasonably-old mice (maybe ~20 mo), measures outcomes ~ 1 week later, then waits at least a couple months before evaluating outcomes again. If persistent senescent cells are both real and relevant, then we’d expect to see relatively little regression in outcomes over time. If persistent senescent cells are not real or not relevant, then we’d expect to see the mice mostly regress to the pre-treatment state after a couple months. (Though they would probably be slightly better off than control mice, since they’d have effectively taken a couple weeks with the core aging feedback loop on pause.)