The article discusses the role of exercise and the transcriptional coactivator PGC-1α in inflammation and chronic diseases. It highlights the link between physical inactivity and the incidence of various chronic diseases, including obesity, cardiovascular diseases, hypertension, type 2 diabetes, certain cancers, pulmonary diseases, immune dysfunction, musculoskeletal disorders, and neurodegenerative disorders. The authors propose that PGC-1α plays a crucial role in controlling muscle plasticity, suppressing inflammatory responses, and mediating the beneficial effects of exercise. Key points include: - Physical activity reduces systemic inflammation, which is linked to many chronic diseases. - PGC-1α is a key regulator of muscle function and adaptation to exercise, promoting muscle fiber switching towards more oxidative and endurance-capable types. - Inactivity leads to a chronic, low-grade inflammatory state, which can exacerbate or cause various diseases. - PGC-1α levels are reduced in inactive individuals, leading to increased expression of pro-inflammatory genes and a higher risk of disease. - Exercise-induced increases in PGC-1α expression can modulate systemic inflammation, potentially reducing the incidence and severity of chronic diseases. - The combination of inactivity and obesity further increases the risk of chronic diseases due to synergistic effects on pro-inflammatory gene expression. The article concludes by suggesting that targeting PGC-1α may have therapeutic potential for various chronic diseases, including muscle wasting, sarcopenia, type 2 diabetes, and muscular dystrophies.The article discusses the role of exercise and the transcriptional coactivator PGC-1α in inflammation and chronic diseases. It highlights the link between physical inactivity and the incidence of various chronic diseases, including obesity, cardiovascular diseases, hypertension, type 2 diabetes, certain cancers, pulmonary diseases, immune dysfunction, musculoskeletal disorders, and neurodegenerative disorders. The authors propose that PGC-1α plays a crucial role in controlling muscle plasticity, suppressing inflammatory responses, and mediating the beneficial effects of exercise. Key points include: - Physical activity reduces systemic inflammation, which is linked to many chronic diseases. - PGC-1α is a key regulator of muscle function and adaptation to exercise, promoting muscle fiber switching towards more oxidative and endurance-capable types. - Inactivity leads to a chronic, low-grade inflammatory state, which can exacerbate or cause various diseases. - PGC-1α levels are reduced in inactive individuals, leading to increased expression of pro-inflammatory genes and a higher risk of disease. - Exercise-induced increases in PGC-1α expression can modulate systemic inflammation, potentially reducing the incidence and severity of chronic diseases. - The combination of inactivity and obesity further increases the risk of chronic diseases due to synergistic effects on pro-inflammatory gene expression. The article concludes by suggesting that targeting PGC-1α may have therapeutic potential for various chronic diseases, including muscle wasting, sarcopenia, type 2 diabetes, and muscular dystrophies.