AgingAug 25, 2026

Blocking insulin signaling in worms greatly extends male lifespan and improves late-life reproductive health

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 26, 2026

Abstract

Ubiquitous degradation of the DAF-2 receptor in male C. elegans increases median lifespan by more than 440%.

Degrading the DAF-2 receptor in the male germline resulted in a decreased lifespan, contrasting with the lifespan extension observed from ubiquitous degradation.
Ubiquitous degradation of DAF-2 significantly prolongs male reproductive health, likely by enhancing the function of the male intromittent organ.
Findings suggest that male C. elegans may provide valuable insights into sex-specific aging mechanisms.
Most aging research has focused on hermaphrodites, highlighting a gap in understanding male-specific aging responses.

Simplified

Males and females are known to have dramatically different health and lifespan trajectories, but the underlying basis for these differences is yet to be fully elucidated. In the Caenorhabditis elegans nematode model system, most aging studies have been conducted with hermaphrodites, and little is known about male-specific responses to pro-longevity mutations. Several previous studies have used the auxin-inducible degron system to degrade the DAF-2/IGF-1 receptor in hermaphrodites, finding that both ubiquitous and tissue-specific degradation can extend lifespan. Here we show that ubiquitous degradation of DAF-2 in male C. elegans increases median lifespan by more than 440%, one of the longest lifespan extensions by a single intervention to date. Conversely, degrading DAF-2 in the male germline decreased lifespan, opposite of its effect in hermaphrodites. Using male mating and reproductive success as a meaningful ecological and neurophysiological measure of healthspan, we found that ubiquitous degradation of DAF-2 greatly prolongs reproductive health, likely by prolonging function of the male intromittent organ in the tail. This work provides further evidence for the importance of studying sex differences in aging and highlights the utility of using C. elegans males to understand the underlying basis of enhanced lifespan and healthspan.

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Blocking insulin signaling in worms greatly extends male lifespan and improves late-life reproductive health

Abstract

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