Rapamycin Extends Lifespan in Every Organism Tested but Causes Immunosuppression in Humans

Rapamycin is the most consistently life-extending drug ever found in lab animals — working in yeast, worms, flies, and mice (10-25% lifespan extension). But it was designed as an immunosuppressant. The Dog Aging Project TRIAD trial ($7M NIH grant, 580 dogs) won't conclude until 2029, and ARPA-H just funded a $30.8M human trial of a next-gen rapamycin analog.

Rapamycin inhibits mTORC1, but at transplant doses also inhibits mTORC2, impairing immune function and glucose homeostasis. Low intermittent doses may spare mTORC2 — Joan Mannick showed low-dose everolimus improved vaccine response by 20% in elderly. ARPA-H PROSPR awarded $30.8M to Cambrian BioPharma for a next-generation oral rapamycin analog selectively inhibiting mTORC1. The Dog Aging Project TRIAD has enrolled 180 of target 580 dogs; $7M NIH grant in 2025 aims to complete enrollment by end of year.

Why It Matters

Estimated 10,000-20,000 people self-medicating with off-label rapamycin for longevity. NIA ITP has shown rapamycin extends mouse lifespan by 10-25%. mTOR dysregulation implicated in cancer, cardiovascular disease, neurodegeneration, and sarcopenia — affecting hundreds of millions.

Startup Approach

Develop tissue-specific mTORC1 inhibitors that spare immune cells, using GalNAc conjugates for liver targeting or other tissue-targeting approaches. Alternatively, build clinical infrastructure for low-dose intermittent rapamycin trials with aging biomarker endpoints.

NIH Funding

NIA ITP ~$6M/year. Dog Aging Project $7M NIH grant (Jan 2025). ARPA-H PROSPR $30.8M to Cambrian BioPharma. NIH Reporter: 500+ active grants mentioning mTOR and aging.

Who's Working On It

Cambrian BioPharma ($30.8M ARPA-H PROSPR), Dog Aging Project TRIAD ($7M NIH), Tornado Therapeutics (Joan Mannick), Aeovian Pharmaceuticals (tissue-selective mTOR inhibitors), NIA Interventions Testing Program