Castration extended lifespan more in adult male mice than in males castrated before puberty (preprint)

Castration extended lifespan more in adult male mice than in males castrated before puberty (preprint)

James Nelson’s group at the University of Texas at San Antonio castrated male mice at 20 days of age (before puberty), 60 days (after puberty), and 240 days (in adulthood). Median lifespan was 841, 887, and 937 days, respectively, compared with 705 days in males that underwent surgery without removal of the testes. The preprint (a manuscript that has not been peer reviewed) appeared on bioRxiv on October 24, 2026, followed by coverage in Science on November 2.

Men have shorter lifespans than women almost everywhere. In the United States, the gap in 2024 was 4,9 years. The testes may contribute to this difference: a genealogical record showed that 81 Korean eunuchs lived an average of 14–19 years longer than uncastrated men of similar social standing, although another researcher questioned the reliability of the records.

Among genetically heterogeneous UM-HET3 mice, females consistently outlive males, paralleling the difference in humans. In a 2023 experiment, Nelson’s group castrated these males before puberty, increasing their median lifespan from 771 to 850 days, matching that of females. What remained uncertain was the age at which testicular factors, including hormones and other substances secreted by the testes, begin to cause harm. If the hormonal surge at puberty establishes the harm, surgery at 60 days, after puberty, would be too late. If harm accumulates from youth, surgery at 240 days, before male mortality begins to rise, would be too late.

Control males had shorter lifespans than those in earlier experiments: their median lifespan was 705 days rather than 771. The authors acknowledge that this may inflate the percentage gains: castration at 240 days increased lifespan by 32,9% relative to 705 days, but by 21,5% relative to 771 days. The difference between surgery at 60 days and surgery at 20 days was not statistically significant. The authors therefore conclude that the hormonal surge at puberty does not shorten male lifespan.

Mortality in males with testes begins to rise at around 240 days, and surgery at that age immediately halted the rise. The preprint’s survival plot shows that, starting a month after surgery, no mice in this group died for about a year. Because surgery at 240 days was still effective, the authors conclude that testicular factors act rapidly and that elevated male mortality depends on their continued presence. Mice that retained their testes until 240 days had lower mortality later in life than mice castrated at 20 days, leading the authors to suggest that the testes may be beneficial before 240 days. The authors tested whether these mice had built up a reserve of strength, but their grip strength and number of signs of frailty were no better than those of mice castrated earlier.

In an analysis of zoo records published in Nature, castration before puberty extended male lifespan more than castration later in life. The preprint authors write that their findings contradict the “earlier is better” model. Michael Garratt of the University of Otago, the first author of that analysis, was not involved in the mouse study. He says of the study: “I am convinced that castration at a later age produces a sustained increase in survival.”

Identifying the harmful testicular factors could make “castration mimetics” possible: interventions that provide the same lifespan benefit without surgery. Because surgery was effective even at 240 days, the authors suggest that these factors could be blocked in adulthood while preserving any benefits they provide earlier in life. According to a review by Nelson’s group, 11 of the 13 compounds that extended mouse lifespan in the ITP testing program had a greater effect in males or worked only in males. The preprint authors suggest that some of these compounds may suppress the harmful effects of the testes. They propose testing compounds in males with and without testes to identify those that act through testicular factors.