MODULE 07 · 60 min

Pharmacology of Healthspan

Rapamycin, metformin, GLP-1s, senolytics — what's real, what's investigational.

In progress

Quiz 0/3

Core summary

Some prescription drugs originally developed for diabetes or transplant patients show signs of slowing aging — but most haven't been proven for that purpose in healthy people. GLP-1 medications (Ozempic, Mounjaro) are reshaping medicine because they reduce weight, heart attacks, kidney decline, and possibly dementia. Don't take prescription drugs for longevity outside a clinical relationship.

Topics covered

01Rapamycin (sirolimus): mTOR inhibition, ITP results, off-label dosing debate
02Metformin: TAME trial design, MILES, biomarker effects
03GLP-1 agonists: cardiovascular, renal, dementia signals
04SGLT2 inhibitors and healthspan endpoints
05Senolytics: dasatinib + quercetin, fisetin
06Statins, ACEi, PCSK9 — established geroprotection through CV risk

Learning objectives

→Summarize the ITP rapamycin lifespan results across replicates.
→Critique the TAME trial design and its multi-morbidity endpoint.
→Discuss GLP-1 receptor agonists' beyond-glycemic outcomes.
→Differentiate evidence levels for senolytic candidates in humans.

Key takeaways

→Rapamycin is the most replicated lifespan-extender in mice — human clinical use is off-label and uncertain.
→Metformin's healthspan effects in non-diabetics remain unproven pending TAME.
→GLP-1s are quietly the most consequential geroscience-relevant drug class of the decade.

Graded claims

Rapamycin extends lifespan in mice

Clinically established — ITP-replicated across sexes and start ages.

Metformin reduces all-cause mortality in non-diabetics

Promising, preliminary — TAME pending; observational signals mixed.

GLP-1 agonists reduce CV mortality in T2D and obesity

Clinically established — SUSTAIN-6, SELECT, STEP trials.

Off-label rapamycin extends human healthspan

Plausible, unproven in humans — Plausible; no RCT evidence yet.

Compounded peptide stacks are FDA-approved longevity therapies

Misleading or false — FDA has issued explicit warnings on compounded peptides.

Quick check

1. Rapamycin's primary molecular target is:

2. TAME trial's primary innovation was:

3. Best-evidenced senolytic combination in human pilots is: