Revisiting mitochondrial dysfunction in aging biology research

Aging is characterized by a persistent decline in function across cells, tissues, and organisms. Given the well-known role of mitochondria in ATP generation, age-related changes in mitochondrial function have been extensively studied in the context of aging and age-related diseases. Although mitochondria are extremely multifunctional, aging research primarily focuses on their bioenergetic role, often assessed through respirometry measurements. Using isolated mitochondrial enzymes, intact mitochondria, intact cells, and permeabilized cells and tissues, researchers have investigated age-related changes in mitochondrial respiratory function in various model species. Findings from these studies remain largely inconsistent, with reports indicating either a decline or no change in mitochondrial respiratory function during aging processes. These variations may depend on factors such as choice of substrates, tissue origin of mitochondria, sex, species, and experimental conditions, making it difficult to establish universal conclusions. Additionally, methodological limitations and inappropriate techniques have further complicated interpretations in the aging field. To advance our understanding, we encourage researchers to acknowledge the intrinsic dynamic nature of mitochondria and their fundamental differences across tissues. Employing an integrated approach that concurrently measures multiple markers of mitochondrial health and bioenergetic status is critical to the comprehensive study of age-related changes in mitochondrial function. Keywords: aging, mitochondrial dysfunction, respiration, mitochondrial membrane potential