Yanxiao Zhang
Regular engagement in physical exercise has been recognized as a formidable non-pharmacological intervention aimed at mitigating age-associated neuroinflammation and neurodegenerative phenomena. A fundamental mechanism that underpins these advantageous effects pertains to the modulation of the NLRP3 inflammasome, which serves as a pivotal regulator of innate immune responses within microglial cells. The aging process is marked by a state of chronic low-grade inflammation, commonly referred to as "inflammaging," which is instigated by mitochondrial dysfunction, oxidative stress, and metabolic disturbances; these factors collectively facilitate the activation of NLRP3 and the subsequent secretion of pro-inflammatory cytokines, notably IL-1β. Contemporary research findings suggest that physical exercise diminishes NLRP3 inflammasome activation through various interrelated pathways. These pathways encompass the reduction of reactive oxygen species production, the inhibition of TXNIP-mediated assembly of the inflammasome, and the modulation of metabolites derived from the gut, such as trimethylamine N-oxide. In addition, factors circulating as a result of exercise, which include irisin and meteorin-like protein, play a significant role in promoting systemic and central anti-inflammatory responses, thereby impacting the functional dynamics of microglia. In experimental paradigms investigating the phenomena of aging and neurodegenerative disorders (NDDs), notably Alzheimer's and Parkinson's diseases, physical activity has been shown to diminish amyloid accumulation, tau pathology, and microglial activation, primarily through the attenuation of NLRP3 signaling pathways. Collectively, these observations underscore the role of exercise as a pivotal regulator of neuroimmune equilibrium, thereby providing mechanistic elucidation of its potential therapeutic efficacy in alleviating inflammaging and decelerating the progression of NDDs.