<p>The global demographic shift towards an aging population has amplified the public health challenge posed by immunosenescence, a progressive remodeling of the immune system that compromises host defenses. This age-related decline is characterized by a reduction in adaptive immunity, marked by a diminished pool of naïve T-cells and an increased susceptibility to infections and poor vaccine responses. Simultaneously, it is defined by a paradoxical state of chronic low-grade inflammation, or “inflammaging,” which accelerates age-related pathologies. This review posits “immunopause” as a conceptual framework for a state of severe immune decline, a state often viewed as an inevitable consequence of aging. However, the evidence synthesized herein challenges this view by positioning physical exercise as a potent, non-pharmacological intervention capable of countering this process. The report systematically reviews the cellular, molecular, and systemic mechanisms through which exercise exerts its beneficial effects, including the rejuvenation of T-cell repertoires, the regulation of cytokine networks, and the modulation of multi-organ axes involving myokines and the gut microbiome. By improving the efficacy of existing immune cells and shifting the systemic inflammatory milieu, chronic physical activity promotes a more “youthful” and functional immune phenotype. This synthesis not only underscores exercise’s potential to enhance vaccine efficacy and serve as an adjuvant therapy for age-related diseases but also argues for a paradigm shift: from viewing immune aging as an immutable process to recognizing it as a modifiable state. The report concludes that exercise provides a scientifically validated strategy to extend healthspan and prevent the pathological state of immunopause.</p>

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“Immunopause” no more: exercise to counter immunosenescence in aging

  • Chen Sun,
  • Jiao Li,
  • Heng Xu,
  • Junying Du,
  • Paramasivam Muthusamy,
  • Kaiyuan Liu,
  • Song Wei,
  • Lulu Zhang

摘要

The global demographic shift towards an aging population has amplified the public health challenge posed by immunosenescence, a progressive remodeling of the immune system that compromises host defenses. This age-related decline is characterized by a reduction in adaptive immunity, marked by a diminished pool of naïve T-cells and an increased susceptibility to infections and poor vaccine responses. Simultaneously, it is defined by a paradoxical state of chronic low-grade inflammation, or “inflammaging,” which accelerates age-related pathologies. This review posits “immunopause” as a conceptual framework for a state of severe immune decline, a state often viewed as an inevitable consequence of aging. However, the evidence synthesized herein challenges this view by positioning physical exercise as a potent, non-pharmacological intervention capable of countering this process. The report systematically reviews the cellular, molecular, and systemic mechanisms through which exercise exerts its beneficial effects, including the rejuvenation of T-cell repertoires, the regulation of cytokine networks, and the modulation of multi-organ axes involving myokines and the gut microbiome. By improving the efficacy of existing immune cells and shifting the systemic inflammatory milieu, chronic physical activity promotes a more “youthful” and functional immune phenotype. This synthesis not only underscores exercise’s potential to enhance vaccine efficacy and serve as an adjuvant therapy for age-related diseases but also argues for a paradigm shift: from viewing immune aging as an immutable process to recognizing it as a modifiable state. The report concludes that exercise provides a scientifically validated strategy to extend healthspan and prevent the pathological state of immunopause.