Social Interaction With Younger Females Extends Lifespan in Aged Male Drosophila melanogaster Independent of Vitamin C

Background: Aging is a multifactorial process shaped by environmental, social, and nutritional influences that collectively drive molecular and physiological decline. The fruit fly Drosophila melanogaster is a well-established model for aging research due to its short lifespan and the conservation of key regulatory pathways across species. While many interventions target single mechanisms, the combined effects of nutritional antioxidants, such as vitamin C, and social interactions on stress responses, lifespan, and functional aging remain insufficiently understood. Therefore, this study aimed to investigate the effects of social interaction and vitamin C supplementation on aging male fruit flies. Methods: The D. melanogaster Oregon R(R) strain was used, with 14-day-old males designated as aged flies and 1–3-day-old females as young flies. This sex-specific design accounted for established differences in lifespan and reproductive biology between males and females. Co-housed groups were maintained on a standard diet with or without vitamin C supplementation at concentrations of 1.25, 2.5, and 5 mM. Lifespan, endurance, and locomotor performance were assessed in aged males. In parallel, reverse transcription quantitative polymerase chain reaction (RT-qPCR) analyses were conducted to examine gene expression across functional categories, including stress response, antioxidant defense, metabolism, and neurotransmitter-related pathways. Results: Co-housing with young females significantly extended the lifespan of aged males, whereas the addition of vitamin C did not confer further benefit. Notably, vitamin C supplementation reduced endurance at certain concentrations, while locomotor activity remained unaffected. Gene expression analyses indicated that the observed lifespan extension was primarily associated with the co-housing condition, characterized by modulation of stress-response pathways and increased expression of ddc, a gene encoding dihydroxyphenylalanine (DOPA) decarboxylase involved in dopamine and serotonin biosynthesis. In contrast, genes related to antioxidant defense and metabolism showed minimal changes. Conclusion: Social interaction with younger individuals extends lifespan in aged male D. melanogaster independent of vitamin C supplementation. These findings suggest may exert a longevity-promoting effect that is not replicated by antioxidant intervention and may involve adaptive, non-antioxidant pathways potentially linked to neurotransmitter-related mechanisms.