Protein acetylation in cardiac aging

Biological aging is attributed to progressive dysfunction in systems governing genetic and metabolic integrity. At the cellular level, aging is evident by accumulated DNA damage and mutation, reactive oxygen species, alternate lipid and protein modifications, alternate gene expression programs, and mitochondrial dysfunction. These effects sum to drive altered tissue morphology and organ dysfunction. Protein-acylation has emerged as a critical mediator of age-dependent changes in these processes. Despite decades of research focus from academia and industry, heart failure remains a leading cause of death in the United States while the 5 year mortality rate for heart failure remains over 40%. Over 90% of heart failure deaths occur in patients over the age of 65 and heart failure is the leading cause of hospitalization in Medicare beneficiaries. In 1931, Cole and Koch discovered agedependent accumulation of phosphates in skeletal muscle. These and similar findings provided supporting evidence for, now well accepted, theories linking metabolism and aging. Nearly two decades later, age-associated alterations in biochemical molecules were described in the heart. From these small beginnings, the field has grown substantially in recent years. This growing research focus on cardiac aging has, in part, been driven by advances on multiple public health fronts that allow population level clinical presentation of aging related disorders. It is estimated that by 2030, 25% of the worldwide population will be over the age of 65. This review provides an overview of acetylation-dependent regulation of biological processes related to cardiac aging and introduces emerging non-acetyl, acyl-lysine modifications in cardiac function and aging.