Comparative Biochemistry and Physiology Part A, Molecular & Integrative Physiology · Jun 25, 2026

A single GPCR locus in Drosophila melanogaster partitions stress physiology by sex

By Lehmann K, Mallick S, Chakkalakkal GJ et al.

Long-lived Drosophila melanogaster mutants can extend the lifespan of the fruit fly by regulating stress resistance, metabolism and nutrient signaling. However, sex differences in stress resistance in relation to longevity in D. melanogaster is not currently evident. The goal of this study was to determine the relationship between sex differences in longevity and stress resistance in D. melanogaster. To investigate this, male and female adult flies of two methuselah mutants (mth²⁴⁸³⁷ and mth²⁷⁸⁹⁶) underwent various stresses and their response was recorded. Our results reveal that the D. melanogaster methuselah mutant female flies have lower fertility and climbing ability, but they are more resistant to starvation and carbon dioxide than methuselah mutant males. In contrast, D. melanogaster methuselah mutant male flies are more resistant to both heat and cold conditions compared to their female counterparts. These findings reveal a sex-specific stress resistance response of D. melanogaster long-lived mutant flies. This information is important because it indicates how different reproductive demands govern the ability of an organism to respond to variable environments, consistent with life-history trade-off theory and the disposable soma hypothesis, which provides a means of deciphering sexual dimorphism in lifespan and trait specific and sex dependent responses to aging. These findings reveal previously unrecognized sex-specific consequences of methuselah disruption across multiple stress-response traits. Although the underlying mechanisms were not examined directly, the observed phenotypic divergence identifies metabolic, endocrine, and neurophysiological pathways as candidate targets for future investigation of sex-specific stress resistance and aging.

doi.org/10.1016/j.cbpa.2026.112041Open accessPubMed 42349712Mechanisms