Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system
What this study shows
Intermittent rapamycin regimens (weekly, or every 5 days) largely spared glucose tolerance, pyruvate tolerance, fasting glucose and insulin, beta-cell function and the immune system, while still inhibiting mTORC1 -- unlike daily dosing, which impaired all of them. IMPORTANT SCOPE: this study measured side effects only. It did NOT measure lifespan or any other benefit endpoint, so it shows the harm can be reduced, not that the benefit is retained. For evidence that a non-continuous schedule preserves a survival benefit, see BIT2016.
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 | 2015 |
| Peer reviewed | Yes |
| Record last updated | 2026-07-29 |
| Source | DOI 10.1111/acel.12405 · PMID 26463117 · Free full text (PMC4717280) |
Extracted findings
| Intervention | Rapamycin – alternative/intermittent dosing regimens |
| Target | mTORC1 (vs mTORC2) |
| Model | Mouse |
| Effect | Intermittent regimens and rapalogs inhibit mTORC1 while largely sparing glucose tolerance and immune function; no survival endpoint was measured |
| Dose | 2 mg/kg rapamycin administered daily (1x/day), weekly (1x/7 days), once every three days (1x/3 days), or once every five days (1x/5 days) to 9-week-old male C57BL/6J mice for 2-8 weeks. |
| Sample size | 9-11 male C57BL/6J mice per treatment group for glucose tolerance tests; 3-6 mice per group for blood rapamycin concentration; 4-9 mice per group for insulin/HOMA2 measurements; 6 mice per treatment for islet analysis. |
| Effect size | Daily rapamycin treatment significantly impaired glucose tolerance (20–116% increase in blood glucose, 71% increase in AUC), while weekly (1x/7 days) or 1x/5 days rapamycin treatment did not impair glucose tolerance. Rapamycin 1x/3 days significantly impaired glucose tolerance. Daily rapamycin inhibited both mTORC1 (S6 S240/244) and mTORC2 (AKT S473) signaling, while weekly rapamycin only inhibited mTORC1. |
| Limitations | No lifespan or healthspan endpoint. Side-effect endpoints only; benefit retention is inferred, not tested. |
In the Atlas
Open questions that cite this study
- Cited as supporting evidence for the open question mTORC1-selective (mTORC2-sparing) dosing captures longevity without insulin resistance.
- Cited as supporting evidence for the open question Rapamycin + AMPK-axis drugs (acarbose / metformin): additive via distinct pathways, and untested as a combination in humans.