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Rapamycin‐mediated mouse lifespan extension: Late‐life dosage regimes with sex‐specific effects

Strong, Randy, Miller, Richard A., Bogue, Molly, Fernandez, Elizabeth, Javors, Martin A., Libert, Sergiy, Marinez, Paul Anthony, Murphy, Michael P., Musi, Nicolas, Nelson, James F., Petrascheck, Michael, Reifsnyder, Peter, Richardson, Arlan, Salmon, Adam B., Macchiarini, Francesca, Harrison, David E.·2020·Aging Cell
DOI 10.1111/acel.13269PMC PMC7681050
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Abstract

To see if variations in timing of rapamycin (Rapa), administered to middle aged mice starting at 20 months, would lead to different survival outcomes, we compared three dosing regimens. Initiation of Rapa at 42 ppm increased survival significantly in both male and female mice. Exposure to Rapa for a 3‐month period led to significant longevity benefit in males only. Protocols in which each month of Rapa treatment was followed by a month without Rapa exposure were also effective in both sexes, though this approach was less effective than continuous exposure in female mice. Interpretation of these results is made more complicated by unanticipated variation in patterns of weight gain, prior to the initiation of the Rapa treatment, presumably due to the use of drug‐free food from two different suppliers. The experimental design included tests of four other drugs, minocycline, β‐guanidinopropionic acid, MitoQ, and 17‐dimethylaminoethylamino‐17‐demethoxygeldanamycin (17‐DMAG), but none of these led to a change in survival in either sex.

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Metadata

Authors
Strong, R., Miller, R. A., Bogue, M., Fernandez, E., Javors, M. A., Libert, S., Marinez, P. A., Murphy, M. P., Musi, N., Nelson, J. F., Petrascheck, M., Reifsnyder, P., Richardson, A., Salmon, A. B., Macchiarini, F., & Harrison, D. E.
Affiliations
  • Geriatric Research, Education and Clinical Center and Research Service South Texas Veterans Health Care System San Antonio TX USA
  • Department of Pathology and Geriatrics Center University of Michigan Ann Arbor MI USA
  • The Jackson Laboratory Bar Harbor ME USA
  • Department of Psychiatry University of Texas Health Science Center at San Antonio San Antonio TX USA
  • Calico Labs South San Francisco CA USA
  • Medical Research Council Mitochondrial Biology Unit University of Cambridge Cambridge UK
  • Geriatric Research, Education and Clinical Center South Texas Veterans Health Care System San Antonio TX USA
  • Department of Cellular and Integrative Physiology Barshop Institute for Longevity and Aging Studies at The University of Texas Health Science Center at San Antonio San Antonio TX USA
  • Department of Molecular Medicine The Scripps Research Institute La Jolla CA USA
  • Department of Biochemistry & Molecular Biology University of Oklahoma Health Science Center Oklahoma City OK USA
  • Division of Aging Biology National Institute on Aging Bethesda MD USA
ORCID
Venue
Aging Cell
Publisher
Wiley
Published
2020-11
Volume
19
Issue
11
ISSN
  • 1474-9718
  • 1474-9726
DOI
10.1111/acel.13269
PMC
PMC7681050
Cited by
92
References
13
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor, 3 d)
Funders
National Institute on Aging (AG013319, AG022303, AG022307, AG022308, AG024824)

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