Aging is a multifactorial process that progressively disrupts cellular and tissue homeostasis, affecting all organ systems at distinct rates and predisposing individuals to chronic diseases such as cancer, type II diabetes, and sarcopenia. Among these systems, skeletal muscle plays a central role in healthspan decline, yet the precise onset of its deterioration remains unclear. Most studies emphasize late-life models, overlooking the transitional phase of middle age, when initial alterations emerge. Evidence indicates that middle-aged muscle exhibits aberrant metabolism, impaired insulin sensitivity, and an early, gradual reduction in mass, suggesting that decline begins long before overt sarcopenia. This narrative review synthesizes current findings on linear and non-linear molecular biomarkers associated with the onset of skeletal muscle aging, aiming to improve early detection of muscular alterations and support the development of interventions that delay or prevent functional decline.

Glioblastoma (GBM) is an aggressive, common brain cancer known to disrupt redox biology, affecting behavior and DNA integrity. Past research remains inconclusive. To further understand this, an investigation was conducted on physical training’s effects on behavior, redox balance, and genomic stability in GBMA models. Forty-seven male C57BL/6J mice, 60 days old, were divided into GBM and sham groups (n = 15, n = 10, respectively), which were further subdivided into trained (Str, Gtr; n = 10, n = 12) and untrained (Sut, Gut; n = 10, n = 15) subsets. The trained mice performed moderate aerobic exercises on a treadmill five to six times a week for a month while untrained mice remained in their enclosures. Behavior was evaluated using open-field and rotarod tests. Post training, the mice were euthanized and brain, liver, bone marrow, and blood samples were analyzed for redox and genomic instability markers. The results indicated increased latency values in the trained GBM (Gtr) group, suggesting a beneficial impact of exercise. Elevated reactive oxygen species in the parietal tissue of untrained GBM mice (Gut) were reduced post training. Moreover, Gtr mice exhibited lower tail intensity, indicating less genomic instability. Thus, exercise could serve as a promising supplemental GBM treatment, modulating redox parameters and reducing genomic instability.

The Developmental Origins of Health and Disease framework proposes that environmental exposures during critical periods of development can shape physiological systems and influence the risk of chronic diseases later in life, including diabetes and metabolic syndrome. Most research on metabolic programming has focused on classical metabolic organs such as the liver, pancreas, and adipose tissue. However, skeletal muscle plays a central role in systemic glucose homeostasis and metabolic flexibility, accounting for the majority of insulin-stimulated glucose uptake in the body. Because muscle metabolism is closely regulated by neural activity through the organization of motor units, the development of the motor neuromuscular axis may represent an underexplored dimension of metabolic programming. This review examines evidence linking early-life metabolic environments to neuromuscular development and discusses how alterations in the maturation of motor neurons, neuromuscular junctions, and muscle fiber phenotype may influence long-term metabolic outcomes. Evidence from epidemiological studies, experimental models, and mechanistic research suggests that maternal metabolic disturbances, including hyperglycemia, obesity, and systemic inflammation, can influence fetal development through metabolic and inflammatory pathways affecting both neural and muscular components of the motor system. These findings support the hypothesis that the motor neuromuscular axis may represent a structural interface linking early developmental exposures to long-term metabolic regulation and risk of metabolic syndrome.

The Developmental Origins of Health and Disease framework proposes that environmental exposures during critical periods of development can shape physiological systems and influence the risk of chronic diseases later in life, including diabetes and metabolic syndrome. Most research on metabolic programming has focused on classical metabolic organs such as the liver, pancreas, and adipose tissue. However, skeletal muscle plays a central role in systemic glucose homeostasis and metabolic flexibility, accounting for the majority of insulin-stimulated glucose uptake in the body. Because muscle metabolism is closely regulated by neural activity through the organisation of motor units, the development of the motor neuromuscular axis may represent an underexplored dimension of metabolic programming. This review examines evidence linking early-life metabolic environments to neuromuscular development and discusses how alterations in the maturation of motor neurons, neuromuscular junctions, and muscle fibre phenotype may influence long-term metabolic outcomes. Evidence from epidemiological studies, experimental models, and mechanistic research suggests that maternal metabolic disturbances, including hyperglycaemia, obesity, and systemic inflammation, can influence foetal development through metabolic and inflammatory pathways affecting both neural and muscular components of the motor system. These findings support the hypothesis that the motor neuromuscular axis may represent a structural interface linking early developmental exposures to long-term metabolic regulation and risk of metabolic syndrome.