bioRxiv : the preprint server for biologyJan 23, 2026

Insulin/IGF-1 Signaling Linked to Four Times Longer Lifespan in Males

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

A canonical IIS-reducing mutation produced an unusually large, male-specific lifespan extension in C. elegans.

Evidence

A preclinical C. elegans study found that the same IIS pathway mutation previously reported to double hermaphrodite lifespan extended male lifespan fourfold to over 110 days and also extended healthspan.

Caveat

The result is limited to a sex-specific worm mutant, with no evidence here that comparable anti-aging effects occur in other animals or humans.

Simplified

The insulin/IGF-1 signaling (IIS) pathway is an evolutionary conserved regulator of longevity, and its modulation is a hallmark of aging research. The 1993 ground-breaking report of amutation (e1370) that reduced IIS and doubledlifespan in hermaphrodite worms paved the way for molecular approaches to modulating aging. However, the impact of that mutation on the male sex has remained largely unstudied. Here we report that the same mutation extends male lifespan by fourfold, to over 110 days. This extreme longevity is coupled with a dramatic extension of healthspan as well. These findings establish sex not as a secondary variable but as a primary determinant of longevity potential, capable of amplifying the output of a core aging pathway to an astonishing degree. This work provides a new approach or dissecting the interplay between sex and aging and suggests that sex-specific interventions may be critical for developing future anti-aging therapeutics. daf-2C. elegans