Supplements for Healthy Aging

An investigational mitochondria-targeting tetrapeptide that binds cardiolipin in the inner mitochondrial membrane. Honest appraisal: it is one of the most rigorously trialed mitochondrial peptides — real Phase 2/3 randomized trials exist — but its pivotal studies were largely negative. The Phase 3 MMPOWER-3 trial in primary mitochondrial myopathy MISSED its primary endpoints, and the EMBRACE-STEMI reperfusion-injury trial failed to reduce infarct size. The clearest positive signals are in the ultra-rare Barth syndrome and in open-label / exploratory data, not in confirmatory trials. It is not an approved drug and not a dietary supplement; grey-market injectable sourcing is unstudied.

A synthetic pineal tetrapeptide (Ala-Glu-Asp-Gly) promoted online as a 'longevity' / telomerase-activating peptide. Honest appraisal: nearly the entire evidence base comes from a SINGLE research group (Khavinson and colleagues at the St. Petersburg Institute of Bioregulation & Gerontology) and is animal-lifespan, cell-culture, and low-rigor human 'geroprotector' reports — with almost no independent replication. The headline 'telomerase activation' rests on one group's fetal-fibroblast experiments, and the human longevity data are mostly on the crude pineal extract (Epithalamin), not the pure peptide. It is NOT a regulated dietary supplement — it is sold injectable 'for research use only'.

A designed senolytic peptide that disrupts the FOXO4–p53 interaction to selectively kill senescent ('zombie') cells. Honest appraisal: the landmark and follow-up evidence is entirely in mice and cell culture — there are no human trials. Sold grey-market for 'anti-aging'; research-use-only.

A mitochondrial-derived peptide (a sibling of MOTS-c) studied for cytoprotection, neuroprotection, and metabolic effects. Honest appraisal: the evidence is almost entirely cell-culture and animal work plus human biomarker associations — there are no human efficacy trials of administered humanin. Research-use-only.

A 16-amino-acid mitochondrial-derived peptide promoted as a metabolic regulator and 'exercise mimetic'. Honest appraisal: the evidence is almost entirely preclinical (mouse and cell studies of AMPK activation, insulin sensitivity, exercise capacity, and bone) plus human ASSOCIATION/observational studies (circulating MOTS-c vs age, metabolic status, exercise). There are essentially NO interventional human trials of administered MOTS-c — nobody has run a randomized trial giving it to people. It is not a regulated dietary supplement; injectable product is sold 'for research use only'.

An injectable analogue of growth-hormone-releasing hormone (the first 29 amino acids of GHRH) that stimulates the pituitary to release growth hormone. Honest appraisal: this WAS an FDA-approved prescription drug (Geref) with real human trials — for diagnosing GH deficiency and treating GH-deficient children — but it was discontinued commercially. Its current marketing as a compounded 'anti-aging' peptide is off-label and is NOT what those trials validated.

A polypeptide complex extracted from the thymus, registered as an immunomodulator medicine in Russia and several CIS countries — so unlike grey-market peptides it has real (if mostly Russian-language and low-quality) human studies. Thymalin is promoted to 'normalize' immune function by stimulating T-lymphocyte differentiation, with claimed uses in respiratory infections, COVID-19 adjuvant therapy, and even longevity. The headline evidence is striking but weak: an open-label Russian cohort reported a 2-fold drop in mortality in elderly people treated with thymalin (± a pineal peptide) over 6-8 years, and unblinded COVID-19 series reported lower hospital mortality when added to standard care. Almost none of this is double-blind, placebo-controlled, or replicated outside Russia/CIS; sample sizes are small; mechanism work is largely in-vitro. Western regulators have NOT approved it. Treat the longevity and mortality claims with strong skepticism.

A synthetic three-amino-acid 'Khavinson' peptide (Glu-Asp-Arg) with only thin, low-quality evidence — almost entirely in-vitro and animal work from a single Russian research group, plus a handful of small, unblinded human 'biological age' reports. Pinealon is marketed as a neuroprotective, anti-aging 'cytogen' bioregulator. Its preclinical literature describes effects on neuron survival, learning, serotonin-related gene expression, and caspase-3 under hypoxic stress — but these come overwhelmingly from one institute, are mostly non-clinical, and have not been independently replicated or tested in rigorous blinded human trials. It is not an approved drug or a regulated dietary ingredient, and the material sold online is an unregulated grey-market peptide. This entry exists to inform, not to recommend.

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.

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 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 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 '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.

NDGA (nordihydroguaiaretic acid; masoprocol) is the main lignan/polyphenol antioxidant of the creosote bush (chaparral, Larrea tridentata) and a classic 5-lipoxygenase inhibitor. It draws longevity interest for a GENUINE, REPLICATED finding: in the NIA's Interventions Testing Program (ITP), NDGA extended lifespan of genetically heterogeneous MALE mice (Strong 2008; first-cohort interim Miller 2007) — which is why it appears in some longevity stacks. But that is an ANIMAL result, in males only, and a later ITP-stock analysis found NO significant lifespan effect (Flurkey 2010). There are essentially NO human trials supporting longevity use. The CRITICAL fact is harm: NDGA / chaparral is HEPATOTOXIC and nephrotoxic — chaparral herbal products caused acute hepatitis, cirrhosis and fulminant liver failure requiring transplant, prompting an FDA warning against chaparral supplements in the 1990s (Sheikh 1997). Animal work also shows it lowers triglycerides and glucose (Scribner 2000), and it has anticancer/anti-inflammatory preclinical interest, but none of that is established human benefit. This is an informational, harm-reduction entry only — NOT a recommendation: a male-mouse-only longevity signal against a serious, documented human liver-injury record.

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 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.