Insights Into the Mechanisms of Biological Aging That Guide Translational and Clinical Research

Understanding the molecular mechanisms of aging guides the development of prevention, intervention, and treatment strategies to reduce the incidence of common age-associated diseases. Over the past decades, the proposed key features (hallmarks) of aging cells have directly or indirectly provided us clues, furthering our understanding of the causes of disease and assisting with the development of therapeutic strategies for diseases such as rare premature aging diseases like Werner syndrome and ataxia telangiectasia (A-T), as well as the common age-related diseases like dementia and sarcopenia. In this editorial, we take a closer look at three of these hallmarks including genomic instability, defective macroautophagy, and mitochondrial dysfunction, and the applications of these concepts in understanding the progress of complex diseases. Mounting studies from the laboratory, supported by emerging clinical evidence, point to the reduction of the oxidized form of nicotinamide adenine dinucleotide (NAD⁺) as a commonality between many of these hallmarks of aging. Intriguingly, stimulating mitochondrial autophagy (mitophagy) via improvement of NAD⁺ availability appears to be a promising and effective therapeutic strategy for many diseases relating to aging. Future studies on the hallmarks of aging should address their internal linkages and clinical interventions.