Rilmenidine as a calorie-restriction mimetic, the data is thinner than the hype
Posted by weekendnate in Research & News - 2 points, 4 comments.
A 2023 paper in Aging Cell found rilmenidine, an older blood pressure med, produced gene expression changes similar to calorie restriction in mice. Futura-Sciences is now calling it an "anti-aging breakthrough."
I'm skeptical. CR mimetics is a cool idea on paper, but mice living a bit longer on a known antihypertensive doesn't translate to humans popping pills and skipping the diet part. The dose used in the animal work was also way higher than what you'd give someone for blood pressure, so we'd be talking about a side effect profile that hasn't been characterized at those levels.
What I want to see is hard endpoints, not just transcript shifts. Does it move anything we actually care about, like insulin sensitivity, lipid panels, or grip strength over a year in older adults? Until then this feels like the longevity press doing what it always does, dressing up a small mechanistic finding as something earth-shaking.
Anyone here actually tried tracking rilmenidine off-label and seen anything move on their bloodwork?
Comments
- dana_n: Agreed on the transcript-vs-endpoint point. Gene expression shifts are a signal, not an outcome, and ive watched a few "breakthroughs" quietly fade once anyone asked for a functional read out. On the dosing question, anecdotally most people who try it off-label seem to land somewhere between 0.5 and 1 mg, but the mouse work used doses that worked out to much more on a per kg basis. Thats a gap worth thinking about, especially for a drug that can drop blood pressure and cause sedation. I wouldnt
- weekendnate: Yeah the dosing gap is what really killed my interest too. 0.5 to 1 mg for BP is one thing, but scaling up to match the mouse exposure means guessing where sedation and hypotension actually start clipping people, and nobody's published that curve. I'd add one more thing to your point: even if the human dose ends up tolerable, a CR mimetic only matters if it moves something like fasting glucose, HOMA-IR, or lipid panels over months. Until someone runs a small trial with those as primary endpoint
- frugal_cooks: Lol "transcript-vs-endpoint" is such a mood, half the peptide world runs on that exact same trick. And yeah the allometric scaling thing on rilmenidine is the part nobody wants to talk about, you basically need a human BP dose that is already sleepy territory and then crank it up, no ma'am.
- weekendnate: Ha, right? Transcript shifts are the "I lost 5 pounds of water weight" of the longevity world, everyone posts the lab pic and skips the DEXA. And yeah, the allometric piece is exactly what bugs me. We are already flirting with sedation at standard BP doses, so pushing past that to hit what the mice got seems like a great way to write a sleepy blog post and tank your next training session. Until someone publishes an actual human trial with endpoints I care about, I am filing this one under inter
Community discussion - research and educational context only. Not medical advice.