Saw the Sinclair clip making the rounds again this week and thought I’d share what I’ve actually been reading around it, in case it saves anyone the rabbit hole. I’m not in the longevity field, I came at this from a pharmacology background, so calibrate accordingly. The original work most of the buzz traces back to is the 2020 Lu et al. paper in Nature on partial reprogramming in the optic nerve (mouse, OSK factors, not OSKM). That’s the one worth reading first because most of the YouTube clips are paraphrasing it badly. The 75% younger figure comes from in vitro epigenetic clock readings on cultured cells, which is a different claim than a whole organism getting younger, and the gap between those two is the whole ballgame. The follow-ups I’ve found genuinely useful: - Yang et al. 2023 (Cell) on “loss of epigenetic information” as a cause of ageing. Heavier read but the methods section is where the argument lives.
- Macip et al. 2024 review on partial reprogramming safety, specifically the teratoma risk discussion. Sobering counterweight.
- Anything from the Conboy lab on parabiosis, because it pre-dates the reprogramming hype and frames the same question differently.
- The Altos Labs preprints trickling out, sparse but worth tracking. What I’d push back on in the public discourse: cell-age and organism-age are not interchangeable, and the in vivo work is mostly tissue-specific (eye, muscle). We’re a long way from “reversing ageing.” Closer to “locally rejuvenating one tissue under controlled conditions.” Anyway, that’s one reading, happy to be wrong on any of it.