Exercise Physiology
Ashrafsadat Anvarimanshadi; Behzad Hajizadeh Maleki; nasrin rafizadeh; Davood Sabour; Elnaz Safikhani; Amirhossein Jafari
Abstract
Aging is influenced by a wide range of biological processes, with increasing attention focused on physical exercise as an effective, non-pharmacological intervention to support healthy aging and extend lifespan. This review examines how exercise influences aging mechanisms by activating Forkhead Box ...
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Aging is influenced by a wide range of biological processes, with increasing attention focused on physical exercise as an effective, non-pharmacological intervention to support healthy aging and extend lifespan. This review examines how exercise influences aging mechanisms by activating Forkhead Box O (FOXO) proteins—especially FOXO3, a critical regulator of oxidative stress resistance, metabolism, and cellular repair. By integrating evidence from both animal models and human studies, we explore how different types of physical activity, including endurance and resistance training, enhance FOXO signaling pathways that govern mitochondrial health, autophagy, and inflammation control. FOXO activation appears to play a central role in mitigating age-related diseases such as sarcopenia, cardiovascular disease, neurodegeneration, and cancer. While preclinical studies consistently demonstrate these protective effects, human data are more variable, highlighting the influence of age, sex, and intervention type. Understanding the molecular connection between exercise and FOXO activity can help develop targeted exercise recommendations to promote longevity and delay age-associated functional decline.
