Captopril; Another Anti-aging Drug, 4% to 5% Lifespan Increase in Females

I just wanted to pull this out to a post by itself so its easier for people to find and track in the future.

In this new paper published by the NIA ITP program Captopril led to a significant, though small (4% or 5%), increase in female lifespan.

Captopril 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.

Captopril led to small (4% or 5%) but significant increases in female lifespan regardless of whether UT mice were included. In male mice, conclusions depend on the degree to which UT (University of Texas) controls are considered a useful standard: p = 0.001 (14% increase) for the three-site dataset, and p = 0.26 (6% increase) for the two-site data. For male mice, the three sites had percent increases in a median of 11, −6, and 28% for TJL, UM, and UT, respectively. We view this as suggestive evidence for lifespan increases in captopril-treated mice.

Captopril is the second ACE inhibitor to be tested by the ITP. The first, enalapril, did not affect survival (Harrison et al., 2009), but other ACE inhibitors have been reported to extend lifespan in male CF-1 mice (Ferder et al., 1993) and female Wistar rats (Santos et al., 2009). Captopril was also found in a drug screen to increase lifespan in C elegans (Kumar et al., 2016). Given the evidence for its efficacy in this study, its clinical uses for hypertension, renal and liver disease, and the fact that other ACE inhibitors have extended rodent lifespan, follow-up studies are warranted to establish replicability and if, replicable, optimal dosage.

Full Paper:

Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice

https://onlinelibrary.wiley.com/doi/10.1111/acel.13724

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Is it only in mice that have higher blood pressure? Can we do cohort analysis of survival rate by pre-existing blood pressure level?

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Also would be interested to learn if it is, having a (very) low blood pressure.

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Code C09 is not totally clean

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The ACE-inhibitor drug captopril inhibits ACN-1 to control dauer formation and aging

Our results indicate that captopril and acn-1 control aging by modulating dauer formation pathways. We speculate that this represents a conserved mechanism of lifespan control.

Brian M Egan, Franziska Pohl, Xavier Anderson, Shoshana C Williams, Imienreluefe Gregory Adodo, Patrick Hunt, Zuoxu Wang, Chen-Hao Chiu, Andrea Scharf, Matthew Mosley, Sandeep Kumar, Daniel L Schneider, Hideji Fujiwara, Fong-Fu Hsu and Kerry Kornfeld

bioRxiv. posted 19 July 2023, 10.1101/2023.07.17.549402