saw this: another gene that makes worms live longer

by Aoife Nguyen

Fight Aging's newsletter yesterday had a study on a gene called MTR4. Turning it up in C. elegans worms extended their lifespan a lot, in the same league as the classic long-lived worm strains and more than most single-gene tweaks manage. There's some mouse work in it too which I haven't read properly yet. Worms are cheap to make live longer though. We've had dozens of these and very few have turned into anything for people. What I'd want to know is what it does to the worms while they're alive. Longer and frailer isn't a win, I've nursed enough of that on nights. Anyone with a lab background know how often worm lifespan genes end up meaning anything in mammals? A rough hit rate would do.

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Farah Weber 1 day ago

Aoife, honest answer: the hit rate is low, but the misses still pay their way. Worm screens are how the insulin/IGF-1 pathway first got linked to ageing, and versions of it keep turning up in mice and in studies of very old people. What usually fails to carry over is the size of the effect. Something that looks dramatic in worms might buy a mouse 10 or 20 percent, in a clean cage. Before I got excited I'd want to see it hold in both male and female mice, and in a second lab. Your frailty question is the right third test. Some long-lived worm strains are sluggish and barely reproduce. The hopeful bit is that MTR4 helps clear out RNA the cell doesn't need. That fits ageing as a maintenance backlog, which is a lot easier to test than a magic switch.

Hannah Schmidt 12 hours ago

Aoife, your frailty point is the one I'd push hardest on, and it's measurable in worms, which people forget. Labs can track how fast a worm moves, how long it keeps pumping its pharynx, how much of its life it spends paralysed at the end. Some long-lived strains look great on survival curves and spend the extra time barely moving. So when I read a paper like this I skip to the healthspan figures before the survival curve. If they aren't there, that tells you something too. On Farah's maintenance framing, I agree and it's the reason I'm cautiously interested. A gene that helps the cell clear out junk RNA is a plausible thing to nudge with a drug one day. "Turn this up and live longer" usually isn't. Mice next, both sexes, and then we'll see.