Short-Chain Fatty Acids: Bridging Gut Microbiota and Systemic Aging—Mechanisms, Interventions, and Current Challenges

Aging is a systemic degenerative process that can lead to functional decline in multiple organs, such as skeletal muscles and the heart, and accelerates the overall aging process through organ-to-organ interactions mediated by metabolites such as short-chain fatty acids (SCFAs). SCFAs serve as a crucial link connecting intestinal health and anti-aging, and their levels and functions undergo significant changes with aging. However, current research lacks understanding of the downstream molecular mechanisms of SCFAs, and intervention methods are mostly limited to simple regulation. This article clarifies the intrinsic relationship between SCFAs and aging from a systemic perspective, analyzes their regulatory mechanisms through key signaling pathways, examines their roles in tissue barrier protection, the improvement of metabolic disorders, and immune regulation, and summarizes their therapeutic potential and diversified intervention strategies in aging-related diseases. The detailed molecular mechanisms by which SCFAs regulate aging are still unclear, and there are no precise intervention plans for different aging stages and organ damage. In the future, we need to utilize techniques such as single-cell sequencing and organ models to explore the regulation of aging cell fates, providing support for the development of metabolite-mediated personalized anti-aging intervention measures.