David Sinclair· PhD
Lowering insulin & mTOR signaling in nematodes extends their lifespan 500%.
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The evidence is convergent. Multiple independent sources reach the same conclusion, the underlying mechanism is well-characterized, and even the field's most cautious voices treat it as worth doing.
Lowering insulin & mTOR signaling in nematodes extends their lifespan 500%.
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those first experiments I did with worms where you know we would knock down the the insulin igf-1 signaling pathway also known as the daf-2 and their worms would live like literally a hundred percent longer or like they don't go from two weeks to four weeks right yeah I mean it was like and not only that like the worms were so youthful like you would look at these worms you know cuz it's all I would do day after day under the microscope is just picking and poking and looking at the worms and how they move and you know as they get older they start to become less mobile
the the natural was a two-week lifespan where for the first week their youthful and then they have a declining health span curve so at the time of their death they're totally decrepit in the experiment you were describing if I'm thinking of the same one you doubled the lifespan and their longevity curve became a square function it just went out kind of yeah exactly yeah that's exactly what happened
the most famous and and one of the first uh genes that was shown to to clearly from a mechanistic perspective affect aging is it comes from cynthia kenyon and even tom johnson a little bit before her which is the insulin-like receptor in c elegans called daf2 and cynthia published a classic paper showing that if you make a mutation in daft ii could double the lifespan of worms and they seem to be healthier about twice as long
When I was doing research at the Salk Institute in La Jolla, before I went to graduate school, I was working on aging and specifically doing different genetic manipulations in C. elegans to look at the effects on aging. So insulin signaling was like obvious. Decrease insulin signaling you're gonna increase this worm's lifespan by, like, up to a 100%, which was, like, very profound.
looking at these worms where you can get rid of their IGF-1, you know, growth signaling pathway and literally can make them live 100% longer.
And I remember the first time I was working with these worms that had a decreased insulin IGF-1 signaling pathway, how they lived like 100% longer and how they were, like, youthful when they were supposed to be dead.