Nutrition is vital for healthy living, yet individual responses to dietary interventions vary widely, complicating our understanding of its effects. Using the Drosophila Genetic Reference Panel (DGRP), we investigated how genetic variation influences responses to diet and aging. We conducted quantitative genetic analyses on lifespan, locomotor activity, dry weight, and heat knockdown time (HKDT), all measured in the same individual flies under control and restricted diets. Flies on the restricted diet exhibited significantly reduced lifespan and dry weight at both 7 and 16 days of age, but showed increased locomotor activity. HKDT was found to be age-dependent. Importantly, we identified significant genotype-by-diet (GDI), genotype-by-age (GAI), and genotype-by-age-by-diet (GADI) interactions across all traits, indicating that both environmental and genetic factors shape trait variation across age and diet. A genome-wide association study revealed a quantita tive trait locus associated with age-dependent dietary response. These findings suggest that genetic susceptibility to environmental influences, such as diet, changes with age. Our results provide new insights into the genetic architecture underlying dietary responses and aging in Drosophila melanogaster, with potential implications for developing personalized dietary interventions to promote healthy aging in humans. The identification of DNA sequence variants linked to age-specific dietary effects opens new avenues for exploring the molecular mechanisms driving these interactions.