Metabolic-Immune Crosstalk as a Driver of Aging and Longevity: An Insight into Drosophila Melanogaster

Abstract

Background: Aging is a complex biological process regulated by interconnected metabolic and immune pathways. Increasing evidence suggests that dysregulation of metabolic–immune crosstalk is a major driver of age-associated functional decline and reduced lifespan. Drosophila melanogaster has emerged as a powerful model system to dissect these interactions due to its conserved metabolic signaling networks and well-characterized innate immune system. Objective: In this context, the study focuses on pathways such as insulin/insulin-like growth factor signaling (IIS), target of rapamycin (TOR), and AMP-activated protein kinase (AMPK) closely interact with innate immune pathways, including Toll, IMD, and JAK/STAT, to influence lifespan and health span. Methods: This review is based on secondary data obtained from peer-reviewed literature accessed through databases including PubMed, ScienceDirect, Google Scholar, ResearchGate, and HINARI. Relevant studies evaluating Drosophila melanogaster, metabolic-immune crosstalk, aging and longevity were critically evaluated. Results: Age-related metabolic imbalance can lead to chronic immune activation, contributing to inflammaging, tissue dysfunction, and reduced longevity. Conversely, immune signaling can reshape metabolic homeostasis by altering nutrient allocation, mitochondrial function, and stress responses. This review highlights current advances in understanding how metabolic and immune pathways integrate to regulate aging in Drosophila melanogaster, emphasizing tissue-specific effects, environmental modulators such as diet and microbiota, and evolutionary trade-offs between immunity and longevity. Conclusions: Elucidating these conserved immune-metabolic mechanisms provides critical insights into the biology of aging and may inform strategies to promote healthy aging across species.