Browse existing research summaries on rapamycin and longevity science.
A whole-organism single-nucleus atlas of rapamycin-treated fruit flies (505,731 nuclei, 181 cell types) identifies a rapamycin-sensitive convergent aging state marked by Fkbp12 and mTORC1-linked metabolism that is reduced more strongly in females, matching their larger lifespan extension.
In a 13-week randomised trial in 40 sedentary adults aged 65 to 85, once-weekly sirolimus 6 mg added to a home exercise programme did not improve chair-stand performance, and the sensitivity analyses suggested it modestly blunted training gains.
A preprint comparing 14 DNA methylation clocks in about 1,000 older adults from the Berlin Aging Study II finds that the DunedinPACE clock tracks cognitive performance and decline most consistently.
A single-arm, open-label pilot trial in 14 people with early Alzheimer's disease: six months of weekly oral rapamycin was tolerated, but glucose metabolism in the pre-specified brain regions did not change.
Design and rationale for a randomised, placebo-controlled rapamycin trial in healthy middle-aged companion dogs — the first rigorous lifespan-and-healthspan test of a pharmacological ageing intervention in dogs.
A meta-analysis of 911 effect sizes from 167 vertebrate studies reports that dietary restriction and rapamycin both extend lifespan, whereas metformin does not.
An open-label phase 1 pilot trial in ten older adults with mild cognitive impairment or early Alzheimer's dementia: eight weeks of low-dose rapamycin was tolerated without serious events, but the drug was not detectable in cerebrospinal fluid and cognition did not change.
A clinical review of geroscience: which ageing pathways can be modified, and how much human evidence currently supports each intervention.
A conference abstract reporting that four weeks of low-dose sirolimus in two cognitively normal middle-aged women carrying APOE4 was followed by higher brain blood flow on MRI.
The published protocol for RAPA-EX-01: a 40-person randomised trial asking whether once-weekly sirolimus 6 mg preserves or blunts the strength and endurance gains of a 13-week home exercise programme in adults aged 65 to 85.
Reports that rapamycin-induced autophagy and lifespan extension depend on a rise in endogenous spermidine, shown across yeast, worms, flies and mice — a mechanism-level result, not a human outcome.
A narrative review of how mTOR overactivation is proposed to link diet, salt intake and the renin-angiotensin-aldosterone system to insulin resistance and hypertension, and which drugs block that pathway.
A systematic review of 33 human biological clocks compares how well methylation-based and clinical-biomarker clocks predict chronological age and mortality, and reports that phenotypic clocks currently predict death better than epigenetic ones.
Reviews how autophagy behaves in the failing heart across ischaemic, pressure-overload, diabetic and drug-induced models, and whether pharmacologic modulators of autophagy such as rapamycin and metformin protect or harm it.
A review of mouse lifespan studies and human trials with rapamycin and rapalogs, arguing that the benefits of mTOR inhibition come from mTORC1 while most of the metabolic side effects come from mTORC2, so lower or intermittent dosing may widen the therapeutic window.
Reviews the mouse evidence that rapamycin extends lifespan and affects age-related conditions including cardiac function, the nervous system, immunity and cell senescence.
Reviews how the two mTOR complexes, mTORC1 and mTORC2, are activated and how they control glucose, amino acid, lipid and mitochondrial metabolism in health, disease and ageing.
In amyloid-overexpressing mice carrying human APOE4, 16 weeks of rapamycin restored blood-brain barrier amyloid clearance, cerebral blood flow and neurotransmitter levels before symptoms appeared, with partly different effects in APOE3 mice.
Argues that rapamycin, like fasting and very low-calorie diets, can raise blood glucose in a reversible form that is not the same as type 2 diabetes, and that the drug mostly prevents diabetic complications in animal studies.
A phase 2a randomised, placebo-controlled trial in 264 adults aged 65 and over reports that six weeks of a low-dose two-drug mTOR inhibitor regimen was associated with fewer self-reported infections over the following year and an improved antibody response to influenza vaccination.
An editorial in Aging argues that longevity depends on communication between organelles and that the TOR pathway acts as the hub linking protein folding, metabolism and mitochondrial function.
In rats doing a resistance-exercise model, rapamycin fully blocked exercise-induced ribosome biogenesis but only partly reduced muscle protein synthesis and the muscle growth produced by four weeks of training.
An Oncotarget editorial arguing that because neurovascular deficits appear in APOE4 carriers before amyloid and tau, reversing them with mTOR inhibition could be a route to preventing Alzheimer's disease.
A short research perspective arguing that dose, delivery route and treatment schedule must be studied to get rapamycin's benefits in mice with fewer side effects.
A review of mTOR biology and rapamycin as an anti-ageing compound argues that many of the drug's side effects are mediated by mTORC2 inhibition and may be separable from its lifespan-extending benefits.
A review of mTOR pathway structure and regulation and of how its dysregulation contributes to cancer, neurological, metabolic and cardiovascular disease, with the mTOR inhibitors approved or in trials for each.
A randomised, observer-blind, placebo-controlled trial in 218 adults aged 65 and over reports that six weeks of low-dose RAD001 improved the antibody response to influenza vaccination and lowered PD-1-positive T cells.
Reviews mTOR inhibition and mammalian longevity, arguing the current evidence best fits lifespan extension mainly through cancer suppression, with symptomatic effects on some ageing traits.
Nine weeks of daily rapamycin in adult mice reduced proliferating neural progenitors in both neurogenic niches and lowered markers of new neurons, whereas metformin given at a dose that also inhibited mTOR in the brain had no such effect.
Reviews the overlap between ageing biology and cardiovascular disease, and why age remains the largest risk factor for cardiovascular disease.
A rat and cell study reports that three weeks of chronic sirolimus treatment lowered body weight and fat mass while causing hyperglycaemia, glucose intolerance and skeletal-muscle insulin resistance.
In 3xTg-AD mice, lifelong rapamycin started at two months of age reduced plaques, tangles and memory deficits, while the same drug started at 15 months changed neither the pathology nor the behaviour.
A mouse study showing that removing the mTOR gene from adult heart muscle causes fatal heart failure, largely through build-up of the protein 4E-BP1.
Cell and mouse-cell experiments report that the longevity-linked deacetylase SIRT1 restrains mTOR signalling, apparently by acting through the TSC1/TSC2 brake on mTORC1.
Cell experiments show that rapamycin pushes human vascular smooth muscle cells toward a mature, contractile state by relieving S6K1-dependent inhibition of IRS-1, an effect that depends on IGF-I and on selective activation of the Akt2 isoform.
A Spanish Society of Nephrology consensus review of how the mTOR inhibitor sirolimus is managed in transplant practice, covering its effects on lipids, blood counts, kidney function, lungs and wound healing, with recommendations for each.
Analyses sirolimus blood levels in kidney transplant recipients and shows how other immunosuppressive drugs taken alongside it change the level reached for a given dose.
