Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice
What this study shows
Mice got rapamycin for only 3 months, starting at 20 to 21 months of age, and were then taken off it. A high injected dose (8 mg/kg a day) raised the males' remaining life expectancy after treatment by 60% (p = 0.02), which is a 16% longer median lifespan counted from birth. In females the same dose did not extend life (p = 0.26), and all 16 treated females examined had aggressive blood-cell tumours of the lymphoma type, against 6 of 12 controls, while other tumour types became rarer. A lower dose in the diet (126 ppm; the injected dose was estimated to equal about 378 ppm) raised post-treatment life expectancy by 42% in both sexes together and median lifespan by 13%, improved grip strength and rotarod performance, and changed the gut bacteria (more segmented filamentous bacteria). Boundary: mice only. The tumour counts come from small groups (12 to 16 per arm), side effects such as cataracts or testis changes were not tested at the dietary dose, and 'life expectancy' is counted from the end of treatment, so it makes the gain look larger than the change in total lifespan.
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 (middle-aged)); 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 (middle-aged) |
| Journal | eLife |
| Year | 2016 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.7554/eLife.16351 · PMID 27549339 · Free full text (PMC4996648) |
Extracted findings
These fields were extracted from the paper with AI assistance and then checked against the source: Cowork session, 2026-10-09 (full text PMC4996648): extraction had lost the sex and dose limits that the curated text carried; corrected.. Where an extracted field and the curated summary above disagree, the curated summary stands.
| Intervention | Rapamycin (transient, 3 months) |
| Target | mTOR |
| Model | Mouse (middle-aged) |
| Effect | A 3-month rapamycin course in middle-aged mice, dose- and sex-dependent: the high injected dose (8 mg/kg) raised male life expectancy up to 60% but did NOT extend female lifespan (and shifted female cancers toward aggressive hematopoietic types); a lower dietary dose (126 ppm) raised survival in both sexes. Healthspan (grip, Rotarod) improved after treatment. |
| Dose | 8 mg/kg rapamycin via intraperitoneal (i.p.) injections daily for 90 days, starting at 20–21 months of age. |
| Sample size | Males: N=18 vehicle, N=17 rapamycin; Females: N=20 vehicle, N=20 rapamycin for survival analysis. |
| Effect size | Male mice: 60% increase in median life expectancy from end of treatment (p=0.02) and 16% increase in overall median lifespan from birth (p=0.03). Female mice: no significant increase in survival (p=0.261), but increased incidence of aggressive hematopoietic cancers (16/16 vs 6/12 controls, p=0.002) and decreased non-hematopoietic neoplasms (1/16 vs 7/12 controls, p=0.004). |
| Limitations | No data on animals that may have died prior to receipt from NIA for lifespan curves. |
In the Atlas
Related topics
Links in the pathway map
- Supports Rapamycin activates Longevity
Open questions that cite this study
- Cited as supporting evidence for the open question Muscle-sparing, pulsed mTORC1 inhibition.
- 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?.
Answers that reference this study
- Discussed in the plain-language answer How is rapamycin dosed in the longevity studies?.
- Discussed in the plain-language answer Does rapamycin extend lifespan in humans?.
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- Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls (2014)
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