The Hidden Dangers of Sedentary Living: Insights into Molecular, Cellular, and Systemic Mechanisms

With the aging of the global population, neurodegenerative diseases are emerging as a major public health issue. The adoption of a less sedentary lifestyle has been shown to have a beneficial effect on cognitive decline, but the molecular mechanisms responsible are less clear. Here we provide a detailed analysis of the complex molecular, cellular, and systemic mechanisms underlying age-related cognitive decline and how lifestyle choices influence these processes. A review of the evidence from animal models, human studies, and postmortem analyses emphasizes the importance of integrating physical exercise with cognitive, multisensory, and motor stimulation as part of a multifaceted approach to mitigating cognitive decline. We highlight the potential of these non-pharmacological interventions to address key aging hallmarks, such as genomic instability, telomere attrition, and neuroinflammation, and underscore the need for comprehensive and personalized strategies to promote cognitive resilience and healthy aging.