Castration reduces mortality and increases resilience in male mice: what is next?

Abstract

This commentary concerns our recent report that prepubertal castration rescued the shorter lifespan of males, using the first mouse line that robustly shows the same shorter longevity with a similar age-variable mortality disadvantage as human males. This model provides a unique opportunity for research to uncover the basis for this clinically important sex difference in aging. Researchers can now identify the hormones involved, the duration of exposure required, and, most important, the cellular and molecular targets, with the ultimate goal of developing therapeutic interventions to enhance health and reduce mortality without castration-compromising reproductive function.

Keywords: Age-specific mortality; Aging; Castration; Interventions; Lifespan; Sex differences.

Fig. 1

Survival data for a ITP historical control mice, and b sham-operated (SHAM) and orchiectomized (ORX) male mice. Correlation between lifespan and body weight at 6 months in c ITP historical control mice, and d SHAM and ORX male mice. (Data and figure adapted from 10.1111/acel.13891.)