Related Experiment Video
Updated: Mar 22, 2026
Orthotopic Ovarian Transplantation Procedures to Investigate the Life- and Health-span Influence of Ovarian Senescence in Female Mice
Published on: February 12, 2018
Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice
Sebastian I Arriola Apelo1, Cassidy P Pumper1, Emma L Baar1
1Department of Medicine, University of Wisconsin-Madison. William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.
Abstract:
Inhibition of the mTOR (mechanistic target of rapamycin) signaling pathway by the FDA-approved drug rapamycin promotes life span in numerous model organisms and delays age-related disease in mice. However, the utilization of rapamycin as a therapy for age-related diseases will likely prove challenging due to the serious metabolic and immunological side effects of rapamycin in humans. We recently identified an intermittent rapamycin treatment regimen-2mg/kg administered every 5 days-with a reduced impact on glucose homeostasis and the immune system as compared with chronic treatment; however, the ability of this regimen to extend life span has not been determined. Here, we report for the first time that an intermittent rapamycin treatment regimen starting as late as 20 months of age can extend the life span of female C57BL/6J mice. Our work demonstrates that the anti-aging potential of rapamycin is separable from many of its negative side effects and suggests that carefully designed dosing regimens may permit the safer use of rapamycin and its analogs for the treatment of age-related diseases in humans.
Insights
Intermittent rapamycin treatment extends lifespan in aging mice, even when started late. This dosing strategy may offer a safer way to use rapamycin for age-related diseases by reducing side effects.
Area of Science:
- Gerontology
- Pharmacology
- Molecular Biology
Background:
- Rapamycin inhibits the mTOR pathway, extending lifespan in model organisms and delaying age-related diseases in mice.
- Rapamycin's clinical use for aging is limited by significant metabolic and immunological side effects in humans.
- An intermittent rapamycin regimen (2mg/kg every 5 days) showed reduced side effects compared to chronic treatment, but its lifespan-extending potential was unknown.
Purpose of the Study:
- To determine if an intermittent rapamycin treatment regimen can extend the lifespan of mice.
- To investigate if late-initiation of intermittent rapamycin therapy retains anti-aging benefits.
Main Methods:
- Female C57BL/6J mice were treated with an intermittent rapamycin regimen.
- The treatment was initiated at 20 months of age, a relatively late stage in the mouse lifespan.
- Lifespan was monitored and compared to control groups.
Main Results:
- Intermittent rapamycin treatment initiated at 20 months of age significantly extended the lifespan of female C57BL/6J mice.
- This lifespan extension occurred despite the late initiation of the treatment.
- The findings suggest a dissociation between rapamycin's lifespan-extending effects and its adverse side effects.
Conclusions:
- Intermittent rapamycin dosing is a viable strategy for extending lifespan in aging mice.
- Late-stage initiation of intermittent rapamycin therapy can still confer significant lifespan benefits.
- Optimized dosing regimens may enable safer therapeutic applications of rapamycin and its analogs for human aging and age-related diseases.
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:22PI3K/mTOR/AKT Signaling Pathway