Document Type

Article

Publication Date

12-1-2022

Publication Title

Aging cell

Keywords

JMG, Mice, Male, Female, Animals, Acarbose, Sirolimus, Captopril, Longevity, Aging

JAX Source

Aging Cell. 2022;21(12):e13724.

Volume

21

Issue

12

First Page

13724

ISSN

1474-9726

PMID

36179270

DOI

https://doi.org/10.1111/acel.13724

Grant

This work was funded in part by NIA grants AG022308 (D.E.H.), AG022303 (RAM), AG066346 (MAB), AG022307, and AG013319 (RS), with important facilities supported by CA034196 (TJL) and AG024824 (UM). RS is supported by a Senior Research Career Scientist Award from the Department of Veterans Affairs Office of Research and Development.

Abstract

Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)-1,3-butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, or the combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led to a longer lifespan than in either of the two prior cohorts of mice treated with Rapa only, suggesting that this drug combination was more potent than either of its components used alone. In females, lifespan in mice receiving both drugs was neither higher nor lower than that seen previously in Rapa only, perhaps reflecting the limited survival benefits seen in prior cohorts of females receiving Aca alone. Capt led to a significant, though small (4% or 5%), increase in female lifespan. Capt also showed some possible benefits in male mice, but the interpretation was complicated by the unusually low survival of controls at one of the three test sites. BD seemed to produce a small (2%) increase in females, but only if the analysis included data from the site with unusually short-lived controls. None of the other 4 tested agents led to any lifespan benefit. The C2017 ITP dataset shows that combinations of anti-aging drugs may have effects that surpass the benefits produced by either drug used alone, and that additional studies of captopril, over a wider range of doses, are likely to be rewarding.

Comments

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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