Geroscience — the study of aging mechanisms as drug targets — is becoming a serious pharmaceutical field. The premise: aging is the primary risk factor for most chronic diseases. If you can slow aging, you prevent heart disease, cancer, diabetes, and cognitive decline simultaneously. Several drugs with existing safety profiles are now being tested as longevity interventions.
## Candidates with Human Evidence
**Rapamycin (mTOR inhibitor)**: The strongest animal evidence of any longevity drug, with extending lifespan up to 60% in mice. Ora Biomedical’s PEARL trial is the largest ongoing RCT of low-dose rapamycin for healthy aging, though results are not yet available. See [Rapamycin and Longevity](https://sunqi.org/rapamycin-longevity-en/).
**Metformin**: The world’s most widely prescribed diabetes drug has attracted longevity attention from epidemiological observations that diabetic patients on metformin show lower rates of certain cancers and cardiovascular disease than non-diabetic controls. The TAME (Targeting Aging with Metformin) trial is a landmark 3,000-participant RCT using composite aging outcomes — the first time the FDA has agreed to aging itself as a trial endpoint. Results expected around 2028. See [TAME trial](https://afar.org/tame-trial/).
**Dasatinib + Quercetin (Senolytics)**: Multiple small human studies show reductions in senescence biomarkers. Larger RCTs in frailty and idiopathic pulmonary fibrosis are ongoing. See [Senolytics](https://sunqi.org/senolytics-anti-aging-en/).
**GLP-1 receptor agonists (semaglutide/Ozempic)**: Best known for weight loss and diabetes, GLP-1 agonists are showing unexpected effects on aging-adjacent mechanisms: reducing systemic inflammation, improving cardiac outcomes, and possibly protecting cognitive function. Multiple 2024 studies report associations between GLP-1 use and reduced Alzheimer’s risk, currently under investigation.
## Research-Stage Candidates
**NAD⁺ precursors (NMN, NR)**: Several large RCTs ongoing; current evidence shows metabolic and muscle function improvements in some trials. See [NMN and Longevity](https://sunqi.org/nmn-longevity-en/).
**Fisetin**: A natural flavonoid with senolytic activity. Low toxicity makes it an attractive component of senolytic combinations under investigation.
**Alpha-ketoglutarate (AKG)**: A TCA cycle intermediate that extended mouse lifespan in a 2020 study. Small human trials are running; larger studies are planned.
**Novel AMPK activators**: Beyond metformin, selective AMPK activators are in preclinical and early clinical stages.
## Partial Cellular Reprogramming
The most ambitious longevity intervention under development is partial cellular reprogramming using Yamanaka factors to reset epigenetic age in adult cells. Altos Labs and Retro Biosciences are the best-funded companies in this space. Core challenges — avoiding tumor formation, achieving in vivo delivery — mean clinical application is many years away.
## The Regulatory Landscape
The FDA has historically not recognized “aging” as a disease, meaning longevity drugs must target specific age-related conditions. The TAME trial’s significance is strategic: demonstrating that metformin delays multiple age-related outcomes simultaneously could open a regulatory pathway for drugs that target aging directly. If TAME succeeds, it may reshape how the FDA evaluates longevity interventions.
For background, see [Hallmarks of Aging](https://sunqi.org/aging-biology-hallmarks-en/) and [Rapamycin](https://sunqi.org/rapamycin-longevity-en/).
