Longevity Drug Evidence-Grade Index
18heavily promoted longevity molecules, graded A–D by one thing only: how much completedhuman clinical evidence exists for each for aging and healthspan — not how heavily it is marketed, and not what it was originally approved for.
Built and medically reviewed by Charles Kamen, MD, board-certified neurologist ·
Of 18 heavily promoted longevity molecules, none has a completed human Phase 3 trial for aging itself— there is no FDA-approved anti-aging drug, so no molecule here reaches Tier A. The closest-to-proven (2 molecules at Tier B, including rapamycin on its mTOR/immune human data and creatineon muscle/strength outcome data) rest on healthspan-relevant human endpoints. Several of the most loudly marketed — Alpha-ketoglutarate, Oxaloacetate, Lithium— are preclinical-only. This index grades the strength and quantity of completed humanevidence for aging-relevant outcomes. It is evidence cartography, not a treatment guide: a tier means a molecule has been studied in people, never that it will work for you. “Studied for” is the question a trial asked, never an outcome.
Why a separate index from our peptide evidence grades? Because the question “does this slow aging?” is different from “is this a peptide?” Many of the molecules people chase for longevity — metformin, rapamycin, NAD+ precursors, resveratrol, senolytics — are not peptides at all (see our molecule classifier). This page grades them on the longevity question specifically, so a molecule's original FDA-approved use is deliberately not counted as evidence for aging. Rapamycin is FDA-approved as an immunosuppressant; that approval does not make it an anti-aging drug, so it is graded here on its completed human healthspan data instead.
How this site grades longevity molecules, in one sentence: we ask what is the most rigorous finishedhuman evidence on record for each molecule for an aging/healthspan-relevant outcome — FDA approval specifically for aging with multiple Phase 3 trials is Tier A (currently unmet), completed human RCTs on healthspan endpoints is Tier B, pilot/observational/small-study human data is Tier C, and animal or laboratory evidence only is Tier D. A registered-but-unfinished trial does not move a molecule up a tier. For the biological framework behind these targets, see our Hallmarks of Aging map.
Why grading longevity evidence separately matters
No molecule is FDA-approved for aging — so the original approval never counts as longevity evidence.
A mouse lifespan result is a hypothesis, not a human fact — preclinical lifespan is Tier D.
Observational data (metformin, glucosamine) is real but confounded — it cannot prove causation.
A registered trial (e.g., TAME for metformin) is not finished evidence; recruitment is not results.
The loudest supplements (AKG, oxaloacetate, trace lithium) are very often the least studied in humans.
Grading evidence is separate from judging efficacy — well-studied is not the same as right for you.
The grading rubric
Each molecule is graded by the highest level of completed human evidence that exists for it for aging / healthspan-relevant outcomes specifically— not its original FDA-approved use.
FDA-approved specifically for an aging/healthspan indication, supported by multiple completed Phase 3 randomized controlled trials. As of 2026, no molecule meets this bar — there is no FDA-approved anti-aging drug.
Not approved for aging, but has one or more completed human RCTs on an aging-relevant endpoint (immune function, body composition, metabolic health, mortality proxy). The strongest tier that exists for longevity molecules today.
Human data exists but is limited to pilot trials, small early-phase studies, or observational cohorts. Often the endpoint is a biomarker (e.g., raising NAD+), not a clinical outcome.
Evidence is animal or laboratory only. Lifespan extension may be shown in mice or worms, but no completed human trial demonstrates a clinical healthspan outcome.
Scope note: an FDA approval for a disease (e.g., sirolimus for transplant, metformin for diabetes, dasatinib for leukemia) is not longevity evidence. This index grades each molecule on its completed human healthspan/aging-relevantdata. A registered-but-not-completed trial (such as TAME for metformin) does not lift a molecule out of its tier — recruitment is not evidence.
The index
| Molecule | Tier | ~Completed human trials (aging-relevant) | Studied for (neutral) | Evidence note |
|---|---|---|---|---|
| Rapamycin / sirolimus (mTOR inhibitor) | B | 2 completed human RCTs on immune endpoints (Mannick 2014, 2018) | Immune function and infection rate in older adults (aging-relevant endpoints) | The strongest human longevity-relevant signal of any molecule on this list. Low-dose mTOR inhibition (everolimus / RTB) improved immune response to flu vaccine and cut infections in elderly adults. Sirolimus is FDA-approved — but as an immunosuppressant for transplant, which is NOT longevity evidence. No human lifespan trial exists. |
| Creatine | B | Multiple completed human RCTs + meta-analyses in older adults | Muscle mass and strength during resistance training in older adults (sarcopenia proxy) | Not glamorous, but it has the most robust completed human outcome data of any "longevity" molecule here — repeated RCTs and meta-analyses show it preserves muscle and strength in older adults. Muscle mass is a strong mortality proxy, which is why it grades Tier B. A dietary supplement, not FDA-approved as a drug. |
| Metformin | C | Large observational cohorts + TAME trial registered (not complete) | All-cause mortality in type 2 diabetes; proposed aging modulation (TAME) | Famously hypothesized as an anti-aging drug. The best-known human signal is observational (metformin-treated diabetics showing lower mortality than sulfonylurea-treated peers, Bannister 2014) — confounded by indication. The targeted TAME aging trial is registered but not complete, so it cannot lift metformin above Tier C for the aging question itself. |
| Dasatinib + quercetin (senolytic combination) | C | 1 completed small human clinical trial (Hickson 2019) | Reducing senescent-cell burden in diabetic kidney disease | Among the first senolytic regimens with completed human data: a small clinical trial showed it lowered senescent cells in adipose/kidney tissue of diabetics. Early and small. Dasatinib is FDA-approved (oncology), but that approval is not longevity evidence. Quercetin and fisetin alone are weaker still. |
| Fisetin | C | Preclinical lifespan data (Yousefzadeh 2018); early human PK/safety; outcome trials active | Senolytic clearance; healthspan in aged models | A flavonoid that extended health/lifespan in aged mice (Yousefzadeh 2018). Human use is ahead of the evidence: completed human data so far is pharmacokinetic/safety, with senolytic-outcome trials still running. Graded Tier C for real-but-preliminary human data — closer to the C/D boundary than rapamycin is. |
| NAD+ precursors — NMN | C | Completed small human RCTs (Yoshino 2021) | Raising blood NAD+; insulin sensitivity in prediabetic women | A 2021 RCT showed NMN improved muscle insulin sensitivity in prediabetic women (Yoshino 2021); it reliably raises NAD+ levels. Clinical-outcome (healthspan/lifespan) evidence does not yet exist. A dietary supplement in regulatory flux, not an FDA-approved drug. |
| NAD+ precursors — NR (nicotinamide riboside) | C | Completed small human trials (Martens 2018) | Raising blood NAD+; safety/tolerability in older adults | Chronic NR supplementation safely elevated NAD+ in healthy middle-aged and older adults (Martens 2018). Like NMN, the endpoint is mostly the biomarker (NAD+), not a clinical outcome. A dietary supplement, not FDA-approved. |
| Resveratrol | C | Multiple completed small human RCTs (e.g., Timmers 2011); results mixed | Metabolic effects in obese humans; sirtuin/nutrient-sensing biology | The original "red wine molecule." Human metabolic trials exist (Timmers 2011 showed calorie-restriction-like metabolic effects in obese men), but results across studies are inconsistent and clinical-outcome evidence is absent. Two decades of hype, modest human payoff. |
| Spermidine | C | Observational cohorts + small human trials; preclinical lifespan (Eisenberg 2016) | Cardiovascular mortality; autophagy and lifespan in preclinical models | A polyamine that extended lifespan and protected the heart in mice (Eisenberg 2016). Human data is observational (dietary spermidine intake linked to lower mortality) plus small wheat-germ trials. Promising biology, preliminary human evidence. |
| Urolithin A | C | Completed human RCT on muscle/mitochondrial endpoints (Singh 2022) | Mitochondrial health, muscle strength, exercise performance | A gut-microbiome derivative that induces mitophagy. A randomized trial showed improved muscle strength and mitochondrial biomarkers in middle-aged adults (Singh 2022). One of the cleaner small-RCT signals in the supplement space, though still biomarker-led. |
| Berberine | C | Completed small human RCTs (Yin 2008 and others) | Glycemic control in type 2 diabetes (metformin-like) | A plant alkalide with metformin-like AMPK activation. Human trials show glycemic benefit in type 2 diabetes (Yin 2008). Anti-aging extrapolation is indirect — it is graded on its metabolic human data, not on any aging-specific trial. |
| Glucosamine (± chondroitin) | C | Observational cohort (NHANES, King 2020) | All-cause mortality (observational); joint health | An NHANES analysis linked glucosamine/chondroitin use to lower all-cause mortality (King 2020). Observational only — it cannot prove causation — but it is one of the few "longevity" associations with population-scale human data. |
| Acarbose | C | Human metabolic trials (approved for type 2 diabetes) | Postprandial glucose control; progression from prediabetes | FDA-approved for type 2 diabetes. Like metformin, it is hypothesized to modulate aging via glucose/insulin pathways, but the human evidence for an aging-specific outcome is indirect. Graded on metabolic, not longevity, trials. |
| Alpha-ketoglutarate (calcium AKG) | D | Preclinical lifespan/morbidity data (Asadi Shahmirzadi 2020); minimal human | Lifespan and healthspan in aging mice; reproductive decline | Extended lifespan and compressed morbidity in aging mice (Asadi Shahmirzadi 2020). Despite heavy marketing of CaAKG "longevity" supplements, completed human outcome data is minimal. Preclinical-dominant. |
| Oxaloacetate | D | Preclinical (C. elegans lifespan); no completed human outcome trial | Lifespan in lower organisms; proposed metabolic/ neuroprotective effects | Marketed as a caloric-restriction mimetic. The lifespan evidence is in worms; human clinical-outcome data is absent. Tier D. |
| Lithium (trace / microdose) | D | Preclinical lifespan (C. elegans); human data is epidemiological only | Lifespan in model organisms; population-level associations | Trace lithium extended lifespan in C. elegans, and some epidemiology links naturally occurring low-dose lithium to longevity markers. No human RCT. Heavily promoted in microdose form well ahead of any completed human evidence. |
| GHK-Cu (copper tripeptide) | C | ~7 human studies, ~1–2 RCTs (topical) | Topical skin appearance / photoaging; wound healing | A crossover with our peptide index. A topical human signal exists for skin aging, but landmark cosmetic trials were industry-sponsored and mixed. Detailed on our peptide evidence-grades page; included here only as a cross-reference. |
| Epitalon / MOTS-c | D | 0 completed human efficacy trials | Aging biomarkers / telomere biology (Epitalon); metabolic biology (MOTS-c) | Crossover entries from our peptide index, both Tier D. Epitalon has no ClinicalTrials.gov registrations; MOTS-c has strong preclinical data but no completed human efficacy trial. See the peptide evidence-grades page for the full notes. |
How this index is built: compiled and reviewed by Charles Kamen, MDfrom ClinicalTrials.gov, PubMed / PubMed Central, and U.S. FDA records. Trial counts are approximate and reflect a point-in-time read of public registries (June–July 2026); the tiers are firm, the exact counts carry the uncertainty. The GLP-1 incretin peptides (semaglutide, tirzepatide) are deliberately excluded here because they are peptides and live on our peptide evidence-grades page; they would be the closest to Tier A by healthspan-relevant proxy, but are not approved for aging.
Scope & compliance:this index grades how much human evidence exists, never whether a molecule “works,” is safe for you, slows aging, or is right for any condition. It contains no doses, no titration schedules, no patient outcomes, and no protocols. Several molecules here are not FDA-approved, and several FDA-approved drugs are used off-label. This is educational information about the state of clinical research — not medical advice. Decisions about any medication or supplement should be made with a licensed physician who can evaluate your individual situation.
How we use evidence grades in your protocol
An evidence grade is not a prescription — but it shapes how a thoughtful physician builds your plan. A Tier B molecule like rapamycin has real human healthspan data behind it, but also real trade-offs (it is an immunosuppressant), so its use is a careful, individualized decision — never a reflexive one. Tier C molecules (metformin, NAD+ precursors, senolytics, spermidine, urolithin A) may be reasonable adjuncts when their human data aligns with your situation and goals. Tier D supplements (AKG, oxaloacetate, trace lithium) are, in most cases, worth waiting on until the human evidence catches up to the marketing.
Practically, that means the grade informs three things: whether something is offered at all, how it is monitored if it is, and what you are told to expect. We do not sell a checkout cart of “longevity stacks.” If a heavily marketed supplement is Tier D, you will hear that directly — along with what an evidence-based alternative looks like for your goals. Care starts with an $88 evaluation and is built around your labs, history, and the actual state of the science. For the full service overview, see physician-led longevity medicine.
Longevity evidence in Las Vegas
The evidence on this page does not change by ZIP code — but the marketing pressure absolutely does. Las Vegas has one of the densest concentrations of concierge and med-spa “longevity” offerings in the country, and the molecules most aggressively sold as anti-aging (alpha-ketoglutarate, oxaloacetate, trace lithium, NAD+ IVs) are very often the ones with the weakest completed human evidence. That is the gap this index exists to close: a single, physician-maintained map of what has actually been studied in people, so a Las Vegas patient can tell the difference between a molecule with human data and a hypothesis with a price tag.
Whether you visit our southeast Las Vegas clinic at Eastern Avenue and the 215 from Henderson, Summerlin, Green Valley, or anywhere in the valley — or meet Dr. Kamen by secure telehealth across Nevada — the grading conversation is identical: what the research shows, what tier it sits in, and what that means for your specific goals. No hype, no stack bundles, no “research use only” compounds. Just an honest, board-certified read on the evidence. Visit our Las Vegas clinic to start.
Selected Research
- Mannick JB, et al. mTOR inhibition improves immune function in the elderly. Sci Transl Med. 2014;6(268):268ra179.
- Mannick JB, et al. TORC1 inhibition enhances immune function and reduces infections in the elderly. Sci Transl Med. 2018;10(449):eaaq1564.
- Bannister CA, et al. Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy. Diabetes Obes Metab. 2014;16(11):1165-1173.
- Yoshino M, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229.
- Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286.
- Timmers S, et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011;14(5):612-622.
- Eisenberg T, et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med. 2016;22(12):1428-1438.
- Singh A, et al. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial. Cell Rep Med. 2022;3(5):100633.
- Hickson LJ, et al. Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin. EBioMedicine. 2019;47:446-456.
- Yousefzadeh MJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018;36:18-28.
- Asadi Shahmirzadi A, et al. Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice. Cell Metab. 2020;32(3):447-456.
- Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712-717.
- King DE, Xirasagar S, Moore A. Glucosamine/Chondroitin and Mortality in a US NHANES Cohort. J Am Board Fam Med. 2020;33(6):827-832.
- Devries MC, Phillips SM. Creatine supplementation during resistance training in older adults—a meta-analysis. Med Sci Sports Exerc. 2014;46(6):1194-1203.
Anchors for specific evidence notes only — human-trial, mechanistic, and trial-design context. Not a treatment claim. Several molecules in this index are not FDA-approved; individual results vary and nothing here is medical advice.
Longevity Drug Evidence FAQ
What is a longevity drug evidence grade?
It is a way of ranking how much completed human clinical research exists for a molecule for aging and healthspan specifically — from FDA approval for an aging indication with multiple Phase 3 trials (Tier A, which no molecule currently meets) down to animal and laboratory data only (Tier D). The grade measures how well-studied a molecule is for the longevity question, never whether it will work for you. An FDA-approved drug like rapamycin is graded here on its completed human healthspan data, not on its transplant-immunosuppression approval.
Is there any FDA-approved anti-aging drug?
No — as of 2026 there is no FDA-approved drug for aging or lifespan, so no molecule on this list reaches Tier A. The closest-by-proxy are the GLP-1 receptor agonists (semaglutide, tirzepatide), which have enormous completed human trial programs for cardiometabolic and weight outcomes — but they are approved for diabetes and obesity, not aging, and they are peptides, so they live on our peptide evidence-grades page. Among the non-peptide longevity molecules, the strongest completed human healthspan data sits at Tier B.
Is rapamycin proven to extend human lifespan?
No — there is no completed human lifespan trial for rapamycin. What exists is stronger than for most longevity molecules, though: two completed randomized trials of low-dose mTOR inhibition (everolimus, then the analog RTB) in older adults showed improved immune function and fewer infections (Mannick 2014, 2018). That is genuine human healthspan-relevant evidence, which is why rapamycin grades Tier B — the highest tier any molecule reaches on this page — but it is not proof that rapamycin extends human life.
Does metformin slow aging in humans?
That is unproven. The frequently cited human signal is observational: people with type 2 diabetes started on metformin appeared to have lower mortality than those on sulfonylureas (Bannister 2014) — a finding confounded by who gets which drug and why. The targeted human aging trial (TAME) is registered but not complete. With only observational data and no finished aging RCT, metformin grades Tier C for the longevity question, despite being FDA-approved (for diabetes).
NMN vs NR — which has better human evidence?
They are roughly even, and both are Tier C. Nicotinamide riboside (NR) has clean completed human pharmacokinetic/safety data showing it reliably raises NAD+ in older adults (Martens 2018). Nicotinamide mononucleotide (NMN) has a completed small RCT showing improved muscle insulin sensitivity in prediabetic women (Yoshino 2021). Neither has clinical-outcome (healthspan or lifespan) evidence. For most people the NAD+ precursor question is a biomarker question, not a proven-outcome question.
Do senolytics like dasatinib + quercetin and fisetin have human evidence?
Some, but it is early. The dasatinib-plus-quercetin combination has a completed small human clinical trial showing it reduced senescent cells in people with diabetic kidney disease (Hickson 2019), which is why it grades Tier C. Fisetin has strong preclinical lifespan data (Yousefzadeh 2018) but completed human data so far is pharmacokinetic/safety, with outcome trials still running — also Tier C, near the C/D boundary. Neither is proven to extend human healthspan yet.
Do resveratrol and spermidine actually work in humans?
There is human data, but it is small and mixed (Tier C). Resveratrol has had two decades of hype; human metabolic trials exist (Timmers 2011 showed calorie-restriction-like metabolic effects in obese men) but results across studies are inconsistent and there is no clinical-outcome evidence. Spermidine extended lifespan and protected the heart in mice (Eisenberg 2016), and observational data links dietary spermidine intake to lower mortality — promising biology, preliminary human evidence. Neither is a proven human longevity intervention.
Are longevity supplements like alpha-ketoglutarate, oxaloacetate, and trace lithium proven?
No — all three are Tier D, meaning their evidence is preclinical (animals or cells) rather than completed human trials. Calcium alpha-ketoglutarate extended lifespan and compressed morbidity in aging mice (Asadi Shahmirzadi 2020) but has minimal completed human data. Oxaloacetate lifespan evidence is in worms. Trace lithium extended lifespan in C. elegans and has only epidemiological human associations. These are often among the most heavily marketed longevity supplements — which is exactly why an honest grade matters.
Why grade evidence for longevity specifically, instead of the drug's FDA-approved use?
Because they are different questions. A molecule can be FDA-approved and extremely well-studied for its original disease indication while having little or no evidence for aging itself. Rapamycin is FDA-approved and extensively studied for transplant immunosuppression — but that approval tells you nothing about whether it slows aging in a healthy person, so this index grades it on its completed human healthspan data instead. Grading the longevity evidence separately is what keeps the index honest.
Is longevity-drug evidence grading relevant in Las Vegas, Henderson, or Nevada?
Yes — the evidence does not change by ZIP code, but the marketing pressure does. Las Vegas has a dense concentration of concierge and med-spa longevity offerings, and the molecules most aggressively sold as "anti-aging" (AKG, oxaloacetate, trace lithium, NAD+ IVs) are frequently the ones with the least completed human evidence. Whether you visit our southeast Las Vegas clinic at Eastern Avenue and the 215 from Henderson, Summerlin, or Green Valley — or meet Dr. Kamen by secure telehealth anywhere in Nevada — the conversation is the same: what the research actually shows, what tier it sits in, and what that means for you.
Related reading: The 12 Hallmarks of Aging → what targets them · Senolytics evidence grades · Biological age tests compared · Peptide Evidence-Grade Index · Is it a peptide? (molecule classifier) · Longevity biomarker ranges
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