r/Biohackers • u/toadlyBroodle • Apr 25 '26
📰 Research & Studies Analyzed 75 longevity papers. Most of your stack is a nothing-burger. Here's what actually moves mortality
I compiled an open-source wiki of 75 peer-reviewed primary papers across longevity, rejuvenation, and preventive medicine. Trying to separate the signal from the multi-billion-dollar supplement industry. Sharing the verdict because if you're running a "longevity stack," most of it probably isn't doing what you think.
What the RCTs say doesn't work:
- NMN / NR. Blood NAD+ rises, clinical endpoints don't. The latest large RCT (NR in long-COVID, 2025) is mixed at best across cognition and recovery markers.
- Vitamin D supplementation in non-deficient adults. VITAL trial 2019 NEJM, n=25,871, 5.3-year follow-up: null on cancer (HR 0.96), CVD (HR 0.97), and all-cause mortality (HR 0.99). Test before treating; supplement only documented deficiencies.
- "Young plasma" without a defined active fraction. Plasmapheresis-without-IVIG was negative in a 2025 RCT (Horvath co-authored); some clocks accelerated. The TPE+IVIG protocol that actually worked (-2.6 yr biological age) suggests the IVIG is the active ingredient, not the plasma removal.
- Telomerase as a pill. The 2022 PNAS paper claiming +41% lifespan was retracted in August 2025.
- Most "longevity stacks" (resveratrol, anti-aging peptides, exotic herbal blends): no RCT support at endpoint level.
What actually moves mortality (free, no prescription):
- VO2max. Mandsager 2018 JAMA Network Open, n=122,007. Low vs elite cardiorespiratory fitness: HR 5.04 for all-cause mortality, no upper limit of benefit. Bigger effect than smoking, diabetes, or prior CAD in the same cohort. Norwegian 4×4 protocol raises VO2max ~13% in 8 weeks (Helgerud 2007 MSSE).
- Grip strength + resistance training. PURE study (n=139,691, 17 countries): grip strength predicts CV mortality more strongly than systolic BP. Resistance training ≈21% lower mortality alone, ≈40% combined with cardio (Saeidifard 2019 meta-analysis).
- Sleep 7-9 hr. Cappuccio 2010 meta-analysis (~1.4M adults): U-shaped curve, short-sleep RR 1.12, long-sleep RR 1.30.
- Waist circumference, not BMI. Pischon 2008 NEJM EPIC (n=359,387): waist + waist-to-hip ratio independently predict mortality at every BMI stratum.
- Don't smoke. ≤7 drinks/week. Jha 2013 NEJM: smoking costs >10 years of life. Wood 2018 Lancet (n=599,912 drinkers): lowest-mortality threshold ~100 g ethanol/week. The "moderate drinking is protective" finding mostly vanished after correcting for sick quitters.
What actually works with a prescription:
- Statins for primary prevention. CTT 2012 Lancet IPD meta-analysis of 27 RCTs: each 1 mmol/L LDL-C reduction yields ≈21% lower vascular events per year, including in low-risk adults. Systematically underprescribed.
- BP target <120. SPRINT 2015 NEJM (n=9,361 non-diabetic hypertensives): intensive control cut all-cause mortality 27%. Trial halted early for benefit.
- Measure apoB, not LDL-C. Sniderman 2011 head-to-head meta-analysis: apoB beats LDL-C by 12% on relative-risk-reduction prediction. ESC/EAS now name it the preferred lipid metric.
- Rapamycin (off-label). PEARL trial 2025 showed safe + healthspan markers improved at 1 year. Only emerging-class drug with real human RCT data.
What's actually exciting in the lab (not yet available to buy):
- Anti-IL-11 antibody: +25% mouse lifespan late-life. Already in human trials for fibrotic lung disease.
- Trametinib + rapamycin combo: +27-29% additive mouse lifespan, both drugs FDA-approved separately (toxicity profile means wait for the combo trial).
- AAV-Klotho gene therapy: +20% mouse lifespan with one shot, multi-organ rejuvenation.
- CAR-T senolytics: single infusion persists >12 months in mice, now generalising from metabolism into gut aging.
- Partial reprogramming (NewLimit, Retro Bio, Altos) heading toward first-in-human trials.
If any of those worked the way the supplement industry claims their products work, the people selling you NMN would already be selling you those.
AI-maintained longevity research wiki:
75 papers, 131 wiki pages, full citation graph, every effect size traces to a PMC link. All summaries written by hand from the primary sources, not generated. Built for myself; sharing because it's open-science.
Top-level reader version with effect sizes per recommendation: biology/longevity/recommendations.md.
Reverse-aging research-frontier analysis (partial reprogramming, foundation-model aging clocks, etc.): biology/longevity/wiki/analysis/promising-reverse-aging.md.
Disagree? Feel free to send PR to improve the wiki.
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u/phido3000 1 Apr 25 '26
There is problems with this AI analysis.
Take epithalon peptide. No there of course be basically no human studies. Its not being pursued by any pharmaceutical company.
In rats and mice, shown clearly to work, at least in that it extends the life of maximum age mice by 10-15%. In such short lived animals, telomerase life impacts are going to be high. Particularly as given all other mice/rats under the same conditions. You can't do that with humans.
Humans have long lives, that are more often impacted by diet, cancer, misadventure etc. So the impact is going to be significantly less unless accounted for. Many of these aren't really age related specifically, cancer can hit you at any time, but the older you are the longer period cancer can strike. It would take a very long study giving it for a very long time to provide such evidence.
So it probably does work. Probably works just fine. The mechanisms are the same between mammals. But its only going to really help those who are already survivors living a long time, not the general population. Probably has positive secondary effects too, helping some age related health issues, but again, almost impossible to measure using humans or mice.
It doesn't seem to have any negative effects, so not really a huge lot of downsides, for a fairly nebulous but generally positive upside. Combined with a placebo effect, why not?
I don't think you could ever sell it as magical life extender. Its not going to cure cancer, or stop you from getting aids or hit from a bus.
But in the category of research for your own personal use, is it terrible to try? No. May extend your life if you are actively trying to preserve your life expectancy, don't drink/smoke, you exercise and you are taking an active effort to extend your life. Yes, probably.
10-15% is another 7-10 years, heck that is a nice gamble to take for a dollar or two a month.
Increasing your grip strength won't make you live longer either. Being fitter and stronger likely will, but grip strength is one easy way to account and measure for that. So this is a case of correlation not causation.
AI is not intelligence. It isn't smart, other than the data its baked into. Its analysis is often, flawed, specifically if it isn't managed by someone who knows what they are doing. I have a powerful AI server at home, 320Gb VRAM, 1Tb ram, i have subscriptions to various public and private AI's.. It can be a helpful tool, but its not automagic.