Aging impacts reproductive health, with reproductive capability declining for both males and females as they age. In males, aging is associated with various physiological alterations including changes in testosterone levels and sperm quality, together with a decrease in libido. According to findings in mice, intermittent fasting (IF) holds potential as a new approach to mitigate the age-associated decline in men’s reproductive health.

Numerous studies have shown that IF—a dietary intervention that restricts the opportunity to eat within specific timeframes—prolongs lifespan and healthspan in many species. Here, Xie and colleagues investigated the effects of IF on age-related changes in reproductive functions using male C57BL/6J mice.

First, the investigators tested the fertility of young and aged male mice (8 and 24 months of age, respectively) subjected to either ad libitum (AL) or IF regimes by mating them with young adult females. Consistent with prior reports, all young males were able to reproduce, while only 38% of the aged AL males sired offspring. By contrast, aged IF males successfully produced offspring in 83% of cases, indicating that IF could largely prevent the aging-related fertility decline in male mice.

Next, to understand the effects of aging and diet on fertility, the team compared sperm quantity and quality, and testosterone levels in young and old mice subjected to both regimes. As expected, aging was associated with decreased sperm counts and velocity, and a decline in testosterone concentration. However, IF failed to prevent these changes in aged mice.

Finally, the team demonstrated that the major determinant limiting fertility in aged male mice was a decline in mating behavior, which could be mitigated by long-term IF. Further experiments revelated IF boosted sexual behavior in aged mice by lowering tryptophan levels in the brain, thereby reducing the serotonergic inhibition associated with aging.

Altogether, these results highlight the complex interplay between diet, metabolism and sexual behavior and identify IF as a new therapeutic approach for sexual desire disorders.

Original reference: Xie, K. et. al. Cell. Metab. (2025). https://doi.org/10.1016/j.cmet.2025.03.001