Nutrition, Reproduction, Stress and Aging: Fifteen Years of our Research in Drosophila
DOI:
https://doi.org/10.15330/jpnubio.12.117-135Keywords:
Drosophila melanogaster, nutrition, insulin/TOR signaling, reproduction, oxidative stress, lifespanAbstract
Research using Drosophila melanogaster has provided fundamental insights into how diet, reproduction, genetics, and environment interact to shape aging. We showed that lifespan and reproductive traits are highly sensitive to nutritional balance, and flies represent an ideal system to disentangle these trade-offs. Across studies, protein-carbohydrate ratios, rather than caloric intake alone, determine whether investment favors reproduction or longevity. Flies naturally select nutrient ratios that maximize fecundity at the expense of survival, while dietary manipulations reveal sex-specific and transgenerational influences on stress resistance, metabolism, and antioxidant defenses. Developmental conditions, including larval diet, sugar identity, and crowding stress, further program adult physiology through insulin/IGF and TOR pathways. Our studies showed that insulin-like peptides provide non-redundant regulation of feeding, macronutrient allocation, and metabolic resilience, with neuromodulators and gut progenitors serving as key integrators of systemic signaling. Mitochondrial function and redox balance are important since expression of alternative dehydrogenases or modulation of CncC/Keap1 reshape stress resistance and lifespan. Studies of environmental toxicants, such as aluminum salts or nitric oxide donors, reveal how oxidative and nitrosative stress impair survival, while interventions like alpha-ketoglutarate or mild mitochondrial uncoupling confer context-dependent protection. Plant extracts, trace elements, and nanomaterials act as hormetic modulators of lifespan, although their benefits are tightly constrained by dose, sex, and diet. More than fifty studies published within fifteen years reveals that nutrition, reproduction, signaling pathways, and environmental exposures converge to determine healthspan, providing mechanistic insights with broad relevance to gerontology and translational biology.
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