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Longevity & exposures · Chapter 2 of 2

Longevity & exposures · The frontier tier

Longevity supplements

The experimental end of the field. These have plausible mechanisms and, in one or two cases, some human data — but none of them are established therapeutics, and this page says so card by card.

Essentials Full guide Exposure register Food & product safety
Read the foundation first. Diet, movement, sleep and the exposures you can actually control matter far more than anything on this page. These are an optional layer on top of that, not a substitute for it, and nothing here is a recommendation to take anything.

This is the only input these recommendations use. It changes the case for creatine in particular, because ε4 carriers show measurably lower brain creatine stores. Leave it blank and you will see the general guidance.

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Longevity supplements

The experimental frontier — emerging compounds with promising mechanisms but varying degrees of human evidence.

Longevity & Healthspan

Frontier

The compounds below represent the cutting edge of healthspan research. Mitopure (Urolithin A) has the strongest human data; NMNH and Apigenin are higher-upside but earlier-stage; creatine monohydrate has the longest safety track record but is included here for its emerging cognitive-longevity case (particularly for APOE ε4 carriers). Use these as a calculated bet on bleeding-edge biochemistry — not as established therapeutics.

Considered but not yet recommended

This guide has reviewed several other popular longevity compounds and decided the evidence is currently too early or too mixed to recommend them. They are not added to the stack above — but they are not dismissed either. If the human outcome data matures, they may be added in future versions of this guide. For transparency:

GlyNAC (glycine + NAC)Baylor College of Medicine pilot data shows improvement in multiple biomarkers of ageing (glutathione, oxidative stress, insulin resistance, gait, cognition) in older adults at 100mg/kg/day glycine + 100mg/kg/day NAC. Promising, but small-sample and not yet replicated by independent groups.
FisetinA flavonoid investigated as a "senolytic" — a compound that selectively clears senescent cells. Preclinical data in mice is striking (extends healthspan/lifespan); human RCTs are ongoing (Mayo Clinic, others) but mature outcome data remains limited. Intermittent high-dose protocols (1500mg × 2 days) are popular but not yet validated.
SpermidineAn autophagy inducer found in wheat germ and aged cheese. Higher dietary spermidine intake is correlated with lower all-cause mortality in observational cohorts. Early RCTs show cognitive signals but supplement-based outcome data is still maturing.
Rapamycin / sirolimusThe most discussed of all — mTOR inhibition extends lifespan in every model organism tested. Off-label human use is increasingly common but human outcome data is still mostly observational. Requires medical supervision; immunosuppressive effects are not trivial. Not a self-administered supplement.
Senolytic combinationsDasatinib + quercetin protocols, fisetin pulses, etc. Strong preclinical signal for selective clearance of senescent cells; human outcome data still maturing. Mayo Clinic and other groups have trials in progress.
Methylene blue (low-dose)Old pharmaceutical repurposed for mitochondrial / cognitive support. Some PK and mechanism data exists at low doses; clinical outcome trials in healthy adults are limited. Worth watching but not recommending.

The threshold for inclusion in this guide is at least one well-designed human RCT showing meaningful biomarker or outcome change, plus a reasonable safety record. The compounds above either don't yet meet that bar (most), or have safety considerations that put them beyond the scope of a self-administered supplement guide (rapamycin in particular).

For UK supplement availability of the above, see the Longevity Box UK main product range — but please read the evidence summaries above before purchasing. Buying a supplement does not strengthen its evidence base.

Environmental load on longevity

The sixteen graded household and environmental exposures that used to sit here now have their own page, so they can grow as new topics are added.

Open the exposures guide →