From aldehyde metabolism to delay aging: targeting ALDH2 as a novel strategy

Aldehydes are molecules that are commonly found in both human physiology and the environment. The accumulation of these substances can lead to the cross-linking of intracellular DNA and proteins, thereby disrupting cellular function and contributing to the processes of premature aging and age-related diseases. Aldehyde dehydrogenase 2 (ALDH2), the key member of ALDH family, is an enzyme responsible for aldehyde metabolism, composed of four identical subunits located within the mitochondrial matrix. Its primary role is to catalyze the oxidation of aldehydes, resulting in the formation of their corresponding acid metabolites. This paper presents a succinct overview of the sources and metabolic pathways of key aldehydes within the human body, compares the various primary enzymes involved in aldehyde metabolism, and explores the structural and functional characteristics of ALDH2. Furthermore, ALDH2 is proposed as a potential therapeutic target for addressing aging and associated diseases. The discussion also includes prospective research avenues, particularly focusing on ALDH2 agonists and aldehyde scavengers designed to enhance the clearance of reactive aldehydes and safeguard cellular functions, thereby mitigating aldehyde-induced cellular damage and potentially delaying the aging process.