Rapamycin / Sirolimus

ID: sirolimus_rapamycin

Aliases: rapamycin, sirolimus, Rapamune, Rapamycin, Sirolimus

Type: compound

Route/form: oral prescription tablet/solution in approved systemic contexts; topical route is separate research/compounded context

Status: approved

Evidence level: approved / labelled

Best data tier: approved label + human controlled/review

Support scope: human

Source types: early_human, human_rct, label

Linked sources: 4

Broad outcomes: Gut / immune / inflammation, Longevity / mitochondrial / redox, Muscle growth / performance / recovery, Skin / wound repair, mTORC / autophagy / nutrient signaling

Reading note: These are curation notes anchored to linked sources, not a clinical recommendation or protocol.

Targets / mechanism

• FKBP12-mediated mTORC1 inhibition
• autophagy and nutrient-sensing modulation
• chronic/high-exposure mTORC2 concern

Optimization domains

• mTORC1
• mTOR
• autophagy
• longevity
• immune aging
• skin aging
• transplant immunosuppression
• exercise adaptation

Research basis

• Sirolimus is the canonical mTORC1 inhibitor and has label-level medical context plus human aging-adjacent trials in immune function, skin, and older adults.
• Elderly immune-function and topical-skin studies provide actual human signals, which is stronger than pure lifespan extrapolation from animals.
• It is the central node for comparing rapalogs, RTB101, AMPK activators, and nutrient-side mTORC1 activators.

Limits, risks, and missing evidence

• Human data do not prove lifespan extension in healthy people, and route/dose/schedule matter enormously.
• mTORC1 is needed for muscle protein synthesis, wound healing, immune function, and reproductive/metabolic signaling; indiscriminate suppression can be counterproductive.
• Label risks include immunosuppression/infection, dyslipidemia, mouth ulcers/stomatitis, edema, impaired wound healing, renal/metabolic issues, and drug interactions.

Risk flags

• prescription only
• immunosuppression
• dyslipidemia
• wound healing impairment
• drug interactions
• route schedule sensitive

Linked papers, labels, and reviews

1. DailyMed label: SIROLIMUS tablet, film coated
   label / dailymed_sirolimus_label
   Official label context for oral sirolimus, an mTOR inhibitor; includes approved indications, route, warnings, and adverse-effect monitoring.
2. mTOR inhibition improves immune function in the elderly
   human_rct / pubmed_mtor_inhibition_elderly_immune_2014
   Randomized elderly-volunteer trial using RAD001/everolimus before influenza vaccination; central human evidence for low-dose rapalog immunosenescence discussions.
3. A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: Immunological, physical performance, and cognitive effects
   early_human / pubmed_rapamycin_older_feasibility_2018
   Small randomized older-adult rapamycin feasibility/safety trial; useful human context but not proof of lifespan extension.
4. Topical rapamycin reduces markers of senescence and aging in human skin: an exploratory, prospective, randomized trial
   early_human / pmc_topical_rapamycin_skin_2019
   Exploratory human topical rapamycin trial with skin-aging/senescence endpoints; route-specific and not evidence for systemic longevity use.