<p>The prevention of age-related disorders is influenced by an intriguing combination of molecular pathways that can be activated through physical exercise. The molecules AMP-activated protein kinase (AMPK), Sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), Irisin, and brain-derived neurotrophic factor (BDNF) are essential to this “anti-aging cycle” because they all support cellular function and maintenance in ways that may eventually delay or reverse the effects of aging even that partially or temporarily. AMPK is a master regulator of metabolism that has been connected to improved cellular repair processes and mitochondrial function. Additionally, it is becoming more well acknowledged that the protein deacetylase SIRT1 plays a significant role in regulating aging and age-related illnesses. It initiates several protective cellular processes by interacting with other longevity pathways, such as the production and release of PGC-1α and Irisin, which regulates mitochondrial biogenesis and function. Activation of the AMPK/SIRT1/PGC-1α/Irisin pathway and physical activity have been shown to regulate BDNF. This review aims to describe features of each component of this AMPK/SIRT1/PGC-1α/Irisin/BDNF pathway revealing how they can be stimulated through several mechanisms, including physical exercise, and how this activation acts as an anti-aging tool.</p>