Rankings / Longevity
Longevity — Supplements
NAD+ precursors, alpha-ketoglutarate, astaxanthin, sulforaphane, GHK-Cu, tretinoin — the over-the-counter longevity supplement aisle.
| # | Compound | Ev | Bn | Sf | Grade · Score |
|---|---|---|---|---|---|
| 1 | Lutein + Zeaxanthin Macular xanthophyll carotenoid | 8 | 6.5 | 9 | A+ 8.2 |
| 2 | Tretinoin (all-trans retinoic acid) Retinoid — RAR agonist | 10 | 10 | 5 | A 8 |
| 3 | Alpha-ketoglutarate (Ca-AKG) TCA cycle intermediate | 6 | 5 | 9 | B+ 7.1 |
| 4 | Astaxanthin Carotenoid antioxidant | 6 | 5 | 9 | B+ 7.1 |
| 5 | Glycine (longevity / metabolic) Amino acid / methionine restriction mimetic | 6 | 5 | 9 | B+ 7.1 |
| 6 | Glycine + NAC (GlyNAC) Amino acid combo | 6 | 5 | 9 | B+ 7.1 |
| 7 | NAD+ / NMN / NR NAD+ precursor | 6 | 5 | 9 | B+ 7.1 |
| 8 | Sulforaphane Nrf2 activator | 6 | 5 | 9 | B+ 7.1 |
| 9 | ACE inhibitors / ARBs (telmisartan / losartan / enalapril) RAAS inhibitor / repurposed cardiometabolic | 6 | 5 | 7 | B- 6.3 |
| 10 | SGLT2 inhibitors (canagliflozin / empagliflozin / dapagliflozin) SGLT2 inhibitor / glucoretic | 6 | 5 | 5 | C+ 5.5 |
| 11 | 17-alpha estradiol Non-feminizing estrogen | 2 | 5 | 7 | C- 4.5 |
| 12 | Censavudine / TPN-101 (LINE-1 suppression) Reverse transcriptase inhibitor (NRTTI) | 2 | 5 | 5 | D+ 3.7 |
| 13 | GDF11 Circulating factor | 2 | 5 | 5 | D+ 3.7 |
| 14 | Klotho Anti-aging protein | 2 | 5 | 5 | D+ 3.7 |
| 15 | C60 (carbon 60 / buckminsterfullerene) Fullerene / antioxidant | 3 | 2 | 4 | D 3.3 |
| 16 | NDGA (nordihydroguaiaretic acid) Plant lignan / ITP geroprotector | 3 | 3.5 | 3.5 | D High-risk profile 3.3 |
| 17 | Plasma exchange / young plasma Dilutional therapeutic | 3 | 3.5 | 3.5 | D High-risk profile 3.3 |
| 18 | Yamanaka factors / partial reprogramming Epigenetic reprogramming | 2 | 5 | 3.5 | D High-risk profile 3.1 |
| 19 | ER-100 (partial epigenetic reprogramming) Partial epigenetic reprogramming | 2 | 8 | 2 | D High-risk profile 2.9 |
This is the over-the-counter longevity aisle — NAD+ precursors, polyphenols, polyamines, senolytics in supplement form. It is also the category where marketing outruns human evidence by the widest margin. Mouse data is everywhere; randomised human outcome data is rare. The rankings here are deliberately conservative: a compound that reliably moves a biomarker still scores as moderate until it shows it changes something you would actually feel or live longer for.
What the human data supports
NAD+ precursors (NMN, NR) reliably raise NAD+ levels in people, a finding replicated in RCTs. No human trial has yet shown that raising NAD+ extends healthspan or lifespan, so these remain at moderate evidence despite mouse results. Randomised urolithin A trials (2019, 2022) report modest improvements in mitochondrial and muscle-endurance markers. Spermidine has observational longevity associations and small memory trials in older adults, without definitive outcome evidence.
The cautionary tale
Resveratrol received extensive attention after early mechanistic findings, but it has poor oral bioavailability and a series of unimpressive or null human trials, resulting in a low score. Fisetin remains almost entirely preclinical, with Mayo Clinic human trials capable of changing its evidence tier. Calcium alpha-ketoglutarate (Ca-AKG) rests on mouse lifespan data plus small, uncontrolled human reports.
Endpoint-specific evidence
Tretinoin earns an A in this category because of strong topical evidence for photoaged skin, not evidence for systemic longevity. Its score illustrates why each "anti-aging" claim must be tied to the endpoint and route that were actually studied.
Frequently asked
Do NMN and NR actually extend lifespan?
They reliably raise NAD+ levels in humans, which is well established. But no human trial has shown they extend lifespan or healthspan — the striking results are from mice and have not translated yet. That gap is why they sit at moderate, not strong, evidence here.
Why does resveratrol rank so low?
Despite the early hype, resveratrol has poor oral bioavailability and a track record of unimpressive or null human trials. The rankings reflect the published human evidence rather than the marketing, so it lands near the bottom of the longevity supplements.
Which longevity supplements have comparatively stronger human evidence?
Urolithin A has randomised human data showing modest improvements in mitochondrial and muscle-endurance markers. Topical tretinoin has a deep evidence base for skin aging specifically, not whole-body longevity. Because the endpoints differ, the profiles are not directly comparable.
Is fisetin a proven senolytic?
Not yet in humans. The senolytic excitement around fisetin rests largely on preclinical work; Mayo Clinic human trials are ongoing, and a positive peer-reviewed readout is what would raise its tier.
Scores reflect the published evidence, not a recommendation to use any compound or protocol. Nothing here is medical advice. How we score →