Preprints.org · Oct 22, 2026

Longevity Peptides and Functional Reserve: An Evidence Audit of Approved Peptides Against the Capacities That Keep Older Adults Independent

By O'Leary RT

Peptides are promoted as longevity and healthy-aging interventions, and US regulators are moving to widen access to unapproved ones. I asked which FDA-approved peptides have improved functional reserve and resilience in aging, measured as loaded function in older adults. Of 144 non-insulin peptide records from three published lists, 93 had current US prescribing information, and 26 of these could act on one of five physiological capacities that sustain reserve: bioenergetic capacity, endocrine signaling, proteostasis and mitochondrial quality control, hormetic stress response, and autonomic regulation. I searched PubMed for each. A peptide counted if a blinded controlled trial in older adults improved a loaded functional outcome such as walking capacity, strength or cognition. Five did, though only one has strong support. Semaglutide, tirzepatide and liraglutide improved walk distance; in two trials the gain rose with weight loss, and strength was not reported. Tesamorelin improved executive function in one trial of older adults. Teriparatide improved mobility after fracture but acts on bone, an actuator, rather than a regulatory capacity. None of the 26 moved a loaded outcome through proteostasis, hormesis or autonomic regulation, the targets claimed for unapproved longevity peptides such as BPC-157 and TB-500, which FDA found poorly characterized and without adequate human data. I set out the product-quality standards any peptide must meet before a clinical claim, and the endpoints that would make a claim about reserve falsifiable. Geroscience trials of peptides should require loaded functional endpoints and report reserve costs such as loss of lean mass and strength.

doi.org/10.20944/preprints202610.2246.v1Open accessInterventions