Best Longevity & Geroscience Compounds

An FDA-approved GLP-1 receptor agonist (Ozempic/Rybelsus for type 2 diabetes, Wegovy for chronic weight management) with genuinely strong, large-RCT evidence for glycemic control and substantial weight loss, plus a cardiovascular-outcomes benefit. Honest appraisal: this is a real prescription medicine with real efficacy AND real risks — a boxed warning for thyroid C-cell tumors, pancreatitis and gallbladder risk, very common GI side effects, and growing concern about grey-market/compounded versions. It is included here for reference only, not as a supplement and not auto-recommended.

An FDA-approved prescription medication (Mounjaro for type 2 diabetes, Zepbound for obesity and obstructive sleep apnea), not a dietary supplement. Honest appraisal: in head-to-head phase-3 trials it is the most effective approved weight-loss drug to date — up to ~21% body-weight loss over 72 weeks and superior to semaglutide — but it is a real medicine with real risks: a boxed warning for thyroid C-cell tumors, common GI side effects, and pancreatitis/gallbladder signals. Do not source or use it outside a prescription.

An investigational once-weekly injectable peptide that activates THREE receptors at once — GIP, GLP-1 and glucagon. Honest framing: in a 48-week phase-2 obesity trial it produced the largest mean weight loss yet reported for an incretin-class drug (about -24% at the top dose), and it cut liver fat dramatically in a MASLD substudy. BUT it is NOT APPROVED anywhere — the first phase-3 trial (a type-2-diabetes trial, TRANSCEND-T2D-1) has now reported but the phase-3 obesity and cardio-kidney-outcome (TRIUMPH) program is still ongoing as of 2026, so long-term safety and hard outcomes are unknown. It is a prescription-pathway drug, not a dietary supplement, and the 'retatrutide' sold grey-market online despite no approval is especially risky.

An SGLT2-inhibitor diabetes drug (Invokana) that lowers glucose by excreting it in urine. It extended lifespan in male mice in the NIA aging program, and the SGLT2 class has strong proven cardiovascular, kidney, and heart-failure benefits in humans. Longevity benefit itself is unproven; carries genital-infection and (rarely) ketoacidosis risks. Prescription drug, not a supplement.

An SGLT2-inhibitor diabetes drug (Jardiance) with the strongest human outcome evidence of its class — it cuts cardiovascular death, heart-failure hospitalization, and kidney-disease progression even in non-diabetics. The most widely used SGLT2 for off-label 'longevity,' though longevity itself is unproven (the lifespan data are for sibling canagliflozin in mice). A prescription drug, not a supplement.

An FDA-approved mTOR-inhibitor immunosuppressant (sirolimus, Rapamune) taken off-label for longevity. It is the most robustly lifespan-extending compound in animal studies across species, but human longevity benefit is unproven — the human data are short-term immune/biomarker trials, and it carries real immunosuppression risks. A prescription drug, not a supplement.

An SGLT2-inhibitor diabetes drug (Farxiga/Forxiga) with broad, robust human outcome evidence — it cuts heart-failure hospitalization and cardiovascular death across the ejection-fraction spectrum and slows kidney-disease progression, including in non-diabetics. The sibling of empagliflozin, used off-label for 'longevity,' though longevity itself is unproven (the lifespan data are for sibling canagliflozin in mice). A prescription drug, not a supplement.

An angiotensin-receptor blocker (Micardis) that is unusual among RAS drugs for also being a partial PPARγ agonist — the receptor that glitazone diabetes drugs target. That dual action gives it a metabolic edge: across head-to-head RCTs and a meta-analysis it improves insulin sensitivity, glucose, and lipids more than other ARBs, which is why it features in geroscience discussions. But it is an approved blood-pressure drug whose proven outcomes are cardiovascular, not a demonstrated lifespan/healthspan benefit — and its own pivotal trials show no superiority over ramipril (ONTARGET) and no recurrent-stroke reduction (PRoFESS). A prescription drug, not a supplement.

A rapamycin analog (rapalog, RAD001) approved as an oncology drug (Afinitor) and transplant immunosuppressant (Zortress). It is the mTOR inhibitor with the cleanest human geroscience signal: randomized trials in older adults showed it improved vaccine response and reduced infections — an immune-aging benefit, NOT demonstrated lifespan extension. A prescription immunosuppressant, not a supplement, and its later phase-3 respiratory-illness sibling trial missed its endpoint.

An angiotensin-receptor blocker (Cozaar) — a first-line blood-pressure drug with proven human stroke-prevention and diabetic-kidney-protection outcomes. Its longevity/geroscience interest is the renin-angiotensin–aging axis plus a striking ANIMAL story: blocking the AT1 receptor dampens TGF-β signaling and restores muscle repair in aged/sarcopenic mice. But the anti-sarcopenia and lifespan benefits remain animal-only — not demonstrated in humans. A prescription drug used off-label, not a supplement.

An oral diabetes drug (alpha-glucosidase inhibitor) that blunts post-meal glucose spikes. It robustly extended lifespan in male mice in the NIA aging program and reduced cardiovascular events in human prevention trials. Human longevity benefit is unproven; the main downside is gas/GI side effects. A prescription drug taken off-label, not a supplement.

An injectable anti-interleukin-1β monoclonal antibody (Ilaris), approved for rare periodic fever syndromes. Famous for the landmark CANTOS trial — the first proof that lowering inflammation alone (without touching lipids) cuts cardiovascular events, validating the 'inflammaging' hypothesis. But CANTOS showed NO all-cause-mortality benefit and MORE fatal infections, and the follow-up cancer trials failed. An extremely expensive prescription biologic, not a supplement.

A first-line type-2-diabetes drug (Glucophage) studied as a geroprotector and the basis of the TAME longevity trial. The human longevity case rests on diabetic-population epidemiology and one large meta-analysis; it is genuinely contested — including evidence it can blunt exercise adaptations. A prescription drug taken off-label, not a supplement.

An oral thiazolidinedione (Actos) diabetes drug that improves insulin sensitivity via PPAR-gamma. It drew geroscience interest after reducing recurrent stroke/MI in insulin-resistant non-diabetics (IRIS) and improving NASH liver histology — but weight gain, fluid retention / heart-failure risk, fracture risk, and a debated bladder-cancer signal keep enthusiasm in check. Prescription drug, not a supplement.

An opioid-antagonist drug (naltrexone) taken off-label at very low doses (~1.5–4.5 mg) for chronic pain, fibromyalgia, and autoimmune/inflammatory conditions. The leading idea is that a brief nightly opioid-receptor blockade triggers a rebound rise in endorphins and dampens glial/TLR4 inflammation. Human trials are mostly small pilots with mixed results — a real but preliminary signal in fibromyalgia, weaker elsewhere. A prescription drug used off-label, not a supplement, and not a proven longevity drug.

An ACE-inhibitor blood-pressure/heart drug studied as a geroprotector by targeting the renin-angiotensin system. ACE inhibition extends lifespan in C. elegans (and captopril specifically modulates a worm aging pathway), and the class has decades of human cardiovascular/kidney-protective evidence — but human longevity itself is unproven. A prescription drug used off-label, not a supplement.

A leukemia chemotherapy drug (tyrosine-kinase inhibitor) used off-label — combined with quercetin (the 'D+Q' protocol) — as a senolytic to clear senescent 'zombie' cells. Animal data are striking and the first small human pilots are promising, but it is a serious cancer drug with significant toxicity and almost no human longevity evidence. Prescription drug, not a supplement.

An MAO-B-inhibitor drug approved for Parkinson's disease and depression, long studied as a longevity/neuroprotection agent. It extended lifespan in some rodent studies (with mixed results across labs), but there is no human longevity evidence, and it carries MAO-inhibitor interaction risks. A prescription drug used off-label, not a supplement.

A grey-market AMPK activator marketed as an 'exercise mimetic' on the strength of a single famous mouse study — Narkar 2008, where 4 weeks of AICAR boosted treadmill running endurance 44% in sedentary mice. That endurance signal has NEVER been shown in humans. The only human trials of AICAR (as the drug acadesine) were for a completely different purpose — protecting the heart during cardiac-bypass surgery — and the large, definitive RED-CABG randomized trial was NEGATIVE. AICAR has poor oral bioavailability (it's injected in studies), is WADA-banned as a doping agent, and is not an approved drug or a regulated supplement. There is no human exercise-performance evidence.

The classic geroprotector candidate that was properly tested — and largely failed. The large ASPREE trial found daily low-dose aspirin did NOT extend disability-free survival in healthy older adults and was associated with more bleeding (and numerically higher mortality). It retains real value in secondary cardiovascular prevention, but for healthy-aging/primary prevention the evidence is negative. A medical drug, not a supplement.

A soccer-ball-shaped carbon molecule (60 carbons) sold by biohackers dissolved in olive oil as a 'longevity' antioxidant. Its entire reputation rests on ONE small 2012 rat study that reported a near-doubled lifespan — a result that has never been replicated. There is no human efficacy or safety data, long-term safety is uncharacterized, it is a photosensitizer under light, and the olive-oil carrier can oxidize. A grey-market research chemical, not a proven longevity therapy.

An abandoned PPARδ agonist 'exercise mimetic' that was NEVER approved — development was halted when long-term animal studies found tumors across multiple organs. There are NO human efficacy trials; the headline endurance result is from mice on a treadmill (Narkar 2008). The only human data is a tiny 2-week lipid/HDL study. It is banned by the World Anti-Doping Agency as a gene-doping agent and is sold only as an unregulated grey-market research chemical. The cancer signal — not the endurance hype — is the real story.

An ancient anti-inflammatory drug (from autumn crocus) for gout and familial Mediterranean fever, now studied as a geroprotector targeting 'inflammaging.' Randomized trials (LoDoCo2, COLCOT) show low-dose colchicine reduces cardiovascular events in coronary disease — proof that dampening chronic inflammation has real outcome benefit. Lifespan itself is unproven. A prescription drug used off-label, not a supplement.

An element and mood-stabilizer drug studied at low doses as a geroprotector and neuroprotectant. Intriguing signals — drinking-water epidemiology links trace lithium to lower mortality and dementia, and it extends lifespan in worms — but human evidence is associational, model-organism results are mixed, and therapeutic lithium has a narrow safety window. A prescription drug used off-label; the OTC microdose form is lithium orotate.

A century-old dye and approved drug for methemoglobinemia, used grey-market at low doses as a mitochondrial 'nootropic' and longevity aid. Small human brain-imaging trials suggest low doses can modestly aid memory/oxygen metabolism; longevity/skin evidence is preclinical. Narrow safe-dose window and real interactions (serotonin syndrome). Off-label/research use, not a supplement.

A natural alkaloid from long pepper (Piper longum), studied as a senolytic and ROS-raising anticancer agent. It selectively kills senescent 'zombie' cells and cancer cells in petri dishes and mice, but ALL of this is preclinical — there is no human efficacy data, and its very poor oral bioavailability is a major limit. A research compound, not a supplement or drug.

A very new preclinical 'exercise mimetic' research chemical with NO human data of any kind — every result below is from mice or cultured cells. SLU-PP-332 is a synthetic agonist of the estrogen-related receptors (ERRα/β/γ), orphan nuclear receptors that drive the mitochondrial/oxidative gene program normally switched on by aerobic exercise. In mice it boosted running endurance and fat oxidation, alleviated diet-induced obesity, and improved heart-failure outcomes — a genuinely interesting mechanism. But it has never been tested in a single human, it isn't an approved drug or a lawful supplement, the original compound isn't even orally bioavailable (mouse studies inject it), and its long-term safety is completely unknown. This entry exists to inform, not to recommend.

A grey-market research chemical marketed as 'exercise in a bottle' — every result is from mice or cells, with NO human trials of any kind. SR9009 ('Stenabolic') is a synthetic agonist of REV-ERB, a circadian-clock nuclear receptor, and in mice it shifted metabolic gene expression, raised energy expenditure, reduced fat mass, and increased running capacity. But it has never been tested in a single human, it is essentially inactive when taken orally (poor bioavailability), and a 2019 PNAS study showed several of its effects persist in mice lacking REV-ERB entirely — meaning they are off-target, not the advertised mechanism. It is not an approved drug or a regulated supplement, it is banned by the World Anti-Doping Agency, and it is sold online with no quality control. This entry exists to inform, not to recommend.

A long-acting PDE5 inhibitor (Cialis) approved for erectile dysfunction, BPH, and pulmonary hypertension, drawing geroscience interest from large observational datasets linking PDE5-inhibitor use to lower all-cause mortality, fewer cardiovascular events, and possibly reduced Alzheimer's risk. The catch: this is association, not causation — there is no longevity RCT. A prescription drug used off-label, not a supplement.

A once-yearly intravenous bisphosphonate for osteoporosis that drew geroscience attention because, in a major fracture trial, it reduced not just fractures but all-cause MORTALITY — a benefit larger than bone effects alone explain. Emerging work suggests immune-modulating and possibly senescence-related effects. The mortality signal is real but not fully understood; human longevity is unproven. A prescription drug, not a supplement.

A 'non-feminizing' stereoisomer of estradiol that extended lifespan in male mice in the NIA aging program — with little estrogenic (feminizing) activity. Honest appraisal: the evidence is entirely animal, the benefit is male-specific (it can harm female reproductive aging), and there are no human data. A research compound, not an approved drug or supplement.

An investigational Bcl-2/Bcl-xL inhibitor and one of the most-used research senolytics — it clears senescent 'zombie' cells in animal models. Striking preclinical data (rejuvenated aged stem cells, reduced tau pathology), but no human longevity trials and a serious dose-limiting toxicity: it crashes platelets (thrombocytopenia). An investigational drug, not a supplement.