1. Aging Cell. 2014 Apr;13(2):273-82. doi: 10.1111/acel.12170. Epub 2013 Nov 19.

Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan
preferentially in males.

Harrison DE(1), Strong R, Allison DB, Ames BN, Astle CM, Atamna H, Fernandez E,
Flurkey K, Javors MA, Nadon NL, Nelson JF, Pletcher S, Simpkins JW, Smith D,
Wilkinson JE, Miller RA.

Author information: 
(1)The Jackson Laboratory, Bar Harbor, ME, 04609, USA.

Four agents--acarbose (ACA), 17-α-estradiol (EST), nordihydroguaiaretic acid
(NDGA), and methylene blue (MB)--were evaluated for lifespan effects in
genetically heterogeneous mice tested at three sites. Acarbose increased male
median lifespan by 22% (P < 0.0001), but increased female median lifespan by only
5% (P = 0.01). This sexual dimorphism in ACA lifespan effect could not be
explained by differences in effects on weight. Maximum lifespan (90th percentile)
increased 11% (P < 0.001) in males and 9% (P = 0.001) in females. EST increased
male median lifespan by 12% (P = 0.002), but did not lead to a significant effect
on maximum lifespan. The benefits of EST were much stronger at one test site than
at the other two and were not explained by effects on body weight. EST did not
alter female lifespan. NDGA increased male median lifespan by 8-10% at three
different doses, with P-values ranging from 0.04 to 0.005. Females did not show a
lifespan benefit from NDGA, even at a dose that produced blood levels similar to 
those in males, which did show a strong lifespan benefit. MB did not alter median
lifespan of males or females, but did produce a small, statistically significant 
(6%, P = 0.004) increase in female maximum lifespan. These results provide new
pharmacological models for exploring processes that regulate the timing of aging 
and late-life diseases, and in particular for testing hypotheses about sexual
dimorphism in aging and health.

© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley
& Sons Ltd.

DOI: 10.1111/acel.12170 
PMCID: PMC3954939
PMID: 24245565  [Indexed for MEDLINE]