Effects of anti-aging diets and exercise on age-related musculoskeletal diseases via gut microbiota modulation.

<h4>Introduction</h4>This review summarizes evidence on how anti-aging diets and exercise influence age-related musculoskeletal diseases through modulation of the gut microbiota. With population aging, these diseases are public health concerns. The gut microbiota regulates bone, joint, and muscle health <i>via</i> the gut‑joint, gut‑bone, and gut‑muscle axis. Few reviews integrate diet-exercise synergy with mechanistic pathways linking microbial changes to tissue outcomes.<h4>Discussion</h4>Anti‑aging dietary strategies, classified into caloric restriction(definition) (ketogenic diet, fasting‑mimicking diet, intermittent fasting, time‑restricted feeding) and isocaloric nutrient restriction (e.g. protein or amino acid restriction), reshape gut microbiota composition and function. Caloric restriction and intermittent fasting reduce inflammation and benefit joint and muscle health, whereas long‑term ketogenic or protein/amino acid restriction may adversely affect bone density and muscle anabolism. Moderate exercise increases microbial diversity, enriches beneficial taxa (Akkermansia, Bifidobacterium), and boosts short‑chain fatty acid (SCFA) production, especially butyrate. Exercise also strengthens intestinal barrier integrity, reduces lipopolysaccharide (LPS)‑induced systemic inflammation, and alleviates osteoarthritis (OA), bone loss, and sarcopenia in preclinical models. Combined diet and exercise may provide greater benefits than either alone. However, most evidence derives from animal or small human studies, and causality remains unclear. Future research should clarify causal mechanisms <i>via</i> multi‑omics and germ‑free models.<h4>Conclusion</h4>This review suggests that both anti-aging diets and moderate exercise may improve age-related musculoskeletal diseases partly through gut microbiota modulation. Given substantial inter‑individual variability, future research should prioritize personalized nutrition and exercise prescriptions tailored to microbiota, genetic background, and lifestyle. These findings inform precision strategies to promote healthy aging.