Evolutionary Insights into Irisin/FNDC5: Roles in Aging and Disease from Drosophila to Mammals

The Irisin/FNDC5 protein family has emerged as a pivotal link between exercise and the prevention of age-associated diseases. Irisin is highly expressed during exercise from skeletal and cardiac muscle cells, playing a critical role in mediating systemic health benefits through its actions on various tissues. However, Irisin levels decline with age, correlating with a heightened incidence of diseases such as muscle weakness, cardiovascular disorders, and neurodegeneration. Notably, the administration of Irisin has shown significant potential in both preventing and treating these conditions. Recently, an Irisin/FNDC5 homolog was identified in an invertebrate Drosophila model, providing valuable insights into its conserved role in exercise physiology. Importantly, Irisin/FNDC5 has been demonstrated to regulate autophagy-a process essential for clearing excessive nutrients, toxic aggregates, and dysfunctional organelles-in both flies and mammals. Dysregulated autophagy is often implicated in age-related diseases, highlighting its relevance to Irisin/FNDC5's functions. These findings deepen our understanding of Irisin/FNDC5's roles and its potential as a therapeutic target for mitigating aging-related health decline. Further studies are needed to elucidate the precise mechanisms by which Irisin regulates autophagy and its broader impact on physiological aging and related diseases.