Molecular and Inflammatory Mechanisms of Age-Related Bone Loss and Muscle Decline

Age-related deterioration of the musculoskeletal system represents a primary driver of functional decline, frailty, and loss of independence in older adults. While osteoporosis and sarcopenia were historically studied as discrete tissue-specific conditions, clinical and biological evidence now establishes bone and skeletal muscle as an interconnected, functional unit. Age-related bone loss and progressive muscle wasting frequently progress in tandem, coalescing into the clinical syndrome of osteosarcopenia.At the biological root of this dual decline lies a shared network of cellular and inflammatory disruptions. Primary among these is chronic low-grade inflammation (‘inflammaging’), driven by the accumulation of senescent cells within bone marrow niches, the periosteum, and skeletal muscle interstitium. The senescence-associated secretory phenotype (SASP), enriched in pro-inflammatory cytokines, chemokines, and matrix metalloproteinases, directly blunts osteoblastogenesis, stimulates osteoclastic bone resorption, impairs satellite cell regenerative capacity, and accelerates myofiber atrophy. Concurrently, mitochondrial dysfunction, altered reactive oxygen species (ROS) dynamics, and lipid infiltration into bone marrow and muscle compromise structural integrity.Critically, bidirectional biochemical and biophysical crosstalk between bone and muscle amplifies this degradation. Myokines (such as myostatin and irisin) and osteokines (such as osteocalcin, sclerostin, and RANKL), along with extracellular vesicles, orchestrate continuous reciprocal regulation. When altered during aging, this signaling loop transforms localized tissue stress into systemic musculoskeletal decline. Dissecting the signaling cascades and paracrine mediators that drive this concurrent loss is essential for designing targeted geroscience interventions that preserve mobility and extend healthspan.This Research Topic invites Original Research, Reviews, Mini Reviews, Methods, and Perspective articles bridging molecular biology, cellular immunology, endocrinology, and translational gerontology. We particularly encourage studies examining shared pathways across bone and muscle, innovative preclinical models, and clinical translation.Contributions of interest include, but are not limited to:1. Contribution of chronic low-grade inflammation, cellular senescence, and SASP factors to osteosarcopenia2. Paracrine and endocrine crosstalk between bone and muscle, including novel osteokines, myokines, and exosomal microRNAs3. Mechanotransduction pathways and mechanosensitive signaling in aging osteocytes and myofibers4. Mitochondrial homeostasis, oxidative stress, and metabolic remodeling in musculoskeletal tissues5. Progenitor cell fate choices governing skeletal stem cells, fibro-adipogenic progenitors, and muscle satellite cells6. Preclinical and clinical evaluation of senotherapeutics, exercise mimetics, anti-inflammatory biologics, and validated circulating biomarkers for early risk detection Topic editors: Abhishek Chandra Source: https://www.frontiersin.org/research-topics/86143/molecular-and-inflammatory-mechanisms-of-age-related-bone-loss-and-muscle-decline