Dietary interventions and molecular mechanisms for healthy musculoskeletal aging.

Over the past decade, extensive efforts have focused on understanding age-associated diseases and how to prolong a healthy lifespan. The induction of dietary protocols such as caloric restriction (CR) and protein restriction (PR) has positively affected a healthy lifespan. These intervention ideas (nutritional protocols) have been the subject of human cohort studies and clinical trials to evaluate their effectiveness in alleviating age-related diseases (such as type II diabetes, cardiovascular disease, obesity, and musculoskeletal fragility) and promoting human longevity. This study summarizes the literature on the nutritional protocols, emphasizing their impacts on bone and muscle biology. In addition, we analyzed several CR studies using Gene Expression Omnibus (GEO) database and identified common transcriptome changes to understand the signaling pathway involved in musculoskeletal tissue. We identified nine novel common genes, out of which five were upregulated (Emc3, Fam134b, Fbxo30, Pip5k1a, and Retsat), and four were downregulated (Gstm2, Per2, Fam78a, and Sel1l3) with CR in muscles. Gene Ontology enrichment analysis revealed that CR regulates several signaling pathways (e.g., circadian gene regulation and rhythm, energy reserve metabolic process, thermogenesis) involved in energy metabolism. In conclusion, this study summarizes the beneficiary role of CR and identifies novel genes and signaling pathways involved in musculoskeletal biology.