Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction

Miller RA, Harrison DE, Astle CM, Fernandez E, Flurkey K, Han M, Javors MA, Li X, Nadon NL, Nelson JF, Pletcher S, …, Strong R · 2014 · Aging cell · Atlas ID MIL2014

What this study shows

Rapamycin's lifespan extension in mice is dose-dependent and greater in females.

Abstract

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Rapamycin, an inhibitor of mTOR kinase, increased median lifespan of genetically heterogeneous mice by 23% (males) to 26% (females) when tested at a dose threefold higher than that used in our previous studies; maximal longevity was also increased in both sexes. Rapamycin increased lifespan more in females than in males at each dose evaluated, perhaps reflecting sexual dimorphism in blood levels of this drug.

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At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mouse); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Mouse
Journal	Aging cell
Year	2014
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1111/acel.12194 · PMID 24341993 · Free full text (PMC4032600)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Rapamycin (dose-response)
Target	mTOR
Model	Mouse (genetically heterogeneous)
Effect	Rapamycin extends lifespan 23-26% in a dose- and sex-dependent way, metabolically distinct from dietary restriction
Dose	Rapamycin in food at 4.7, 14, or 42 ppm, administered from 9 months of age until death.
Sample size	Pooled data from 3 sites: 300 control males, 156 males per rapamycin dose group; 280 control females, 136 females per rapamycin dose group.
Effect size	Highest dose (42 ppm) increased median lifespan by 23% in males (P<0.0001) and 26% in females (P<0.0001); all three doses extended lifespan in females, and the two highest doses extended lifespan in males.
Limitations	Lower statistical power for site-independent analyses; Gompertz parameter estimates should be interpreted with caution due to small data sets, low statistical power, and no adjustment for site-to-site variation; increased fighting (11-22% cages removed) in highest dose male group with unknown cause.

In the Atlas

Open questions that cite this study

Cited as supporting evidence for the open question Does mTORC1-selective dosing extend lifespan, and is rapamycin's glucose intolerance a cost at all?.
Cited as supporting evidence for the open question Does the larger rapamycin benefit in female mice survive equal drug exposure, and is it set by hormones or by chromosomes?.

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