This is nice! I like seeing all the different subfields of research listed and compared; as a non-medical person I often just hear about one at a time in any given news story, which makes things confusing.
Some other things I hear about in longevity spaces: - Senescent-cell-based theories and medicines—what’s up with these? This seems like something people were actually trying in humans; any progress, or is this a dud? - Repurposing essentially random drugs that might have some effect on longevity—most famously the diabetes drug metformin (although people aren’t expecting a very large increase in lifespan from this, rather at best a kind of proof-of-concept), also the immunosuppresant rapamicyn. Anything promising here, or is this all small potatoes compared to more ambitious approaches like cellular reprogramming?
I enjoyed this other LessWrong post trying to investigate root causes of aging, which focuses more on macro-scale problems like atheroschlerosis (although many of these must ultimately driven by some kind of cellular-level problems like proteins getting messed up via oxidization).
Senescent-cell-based therapeutics feels like somewhat of a dead-end...senescence happens for a reason, and clearing out these cells have some second-order downsides. E.g., the inflammation caused by senescence is important for acute injury repair. I am less well-read on this area though!
Metformin and rapamicyn are promising in the same way ozempic is promising; helping curtail metabolic problems helps a LOT of things, but it won’t lead to dramatic changes in lifespan. Definitely in healthspan! But even there, nothing insane.
Imo, partial cellular reprogramming is the only real viable approach we have left, I’m kinda unsure what else the field has to offer if that ends up failing.
I have a pet theory that… I don’t see a way to implement *in vivo*, but I’d like to float in case it has any value.
The gist is the notion of self-copying genes that progressively pollute each cell lineage’s genome over decades. (And the explanation for why this doesn’t just accumulate across generations and end the species would be some combination of polluted sperm failing to outcompete surrounding healthier sperm on average, and polluted embryos being sufficiently more likely to miscarry.)
And the related solution (and experiment) would be editing gametes or zygotes to lack all copies of the self-copying gene, so that there’d be none of them to initiate the process of runaway self-copying gene accumulation. In the worlds where this idea leads to longevity escape velocity, it’d need to be upstream of the other pieces of aging, which… I’m guessing not all of them, but maybe enough? It’s based on the “retrotransposons” idea, from the literature.
I… have neither the knowledge nor the resources to go looking myself, yet, but it felt worth pointing out that hypothetically there might be avenues left to explore, if cellular reprogramming isn’t enough.
This is nice! I like seeing all the different subfields of research listed and compared; as a non-medical person I often just hear about one at a time in any given news story, which makes things confusing.
Some other things I hear about in longevity spaces:
- Senescent-cell-based theories and medicines—what’s up with these? This seems like something people were actually trying in humans; any progress, or is this a dud?
- Repurposing essentially random drugs that might have some effect on longevity—most famously the diabetes drug metformin (although people aren’t expecting a very large increase in lifespan from this, rather at best a kind of proof-of-concept), also the immunosuppresant rapamicyn. Anything promising here, or is this all small potatoes compared to more ambitious approaches like cellular reprogramming?
I enjoyed this other LessWrong post trying to investigate root causes of aging, which focuses more on macro-scale problems like atheroschlerosis (although many of these must ultimately driven by some kind of cellular-level problems like proteins getting messed up via oxidization).
Thank you for reading!
Senescent-cell-based therapeutics feels like somewhat of a dead-end...senescence happens for a reason, and clearing out these cells have some second-order downsides. E.g., the inflammation caused by senescence is important for acute injury repair. I am less well-read on this area though!
Metformin and rapamicyn are promising in the same way ozempic is promising; helping curtail metabolic problems helps a LOT of things, but it won’t lead to dramatic changes in lifespan. Definitely in healthspan! But even there, nothing insane.
Imo, partial cellular reprogramming is the only real viable approach we have left, I’m kinda unsure what else the field has to offer if that ends up failing.
I have a pet theory that… I don’t see a way to implement *in vivo*, but I’d like to float in case it has any value.
The gist is the notion of self-copying genes that progressively pollute each cell lineage’s genome over decades. (And the explanation for why this doesn’t just accumulate across generations and end the species would be some combination of polluted sperm failing to outcompete surrounding healthier sperm on average, and polluted embryos being sufficiently more likely to miscarry.)
And the related solution (and experiment) would be editing gametes or zygotes to lack all copies of the self-copying gene, so that there’d be none of them to initiate the process of runaway self-copying gene accumulation. In the worlds where this idea leads to longevity escape velocity, it’d need to be upstream of the other pieces of aging, which… I’m guessing not all of them, but maybe enough? It’s based on the “retrotransposons” idea, from the literature.
I… have neither the knowledge nor the resources to go looking myself, yet, but it felt worth pointing out that hypothetically there might be avenues left to explore, if cellular reprogramming isn’t enough.