Posttranslational Modifications of Lamin A/C and Cardiac Aging: A Short Review

Cardiac aging is considered as natural and age-related changes in the heart, which can lead to a decline in heart function. Cardiac aging increases the risk of heart failure, atrial fibrillation, and other cardiovascular complications. Understanding the molecular and cellular mechanisms of cardiac aging is crucial for preventing and managing age-related heart problems. Among nuclear lamins, Lamin A/C (LMNA) is the most studied protein linked to cardiac aging. LMNA protein, the alternative splice product of LMNA gene, is crucial for maintaining nuclear inner membrane structure, regulating expression of different genes, chromatin organization, and cell division. A mutation in LMNA gene causes progeria, a rare genetic disorder that causes premature aging and cardiovascular diseases. In addition to progeria, muscular dystrophy, lipodystrophy, and cardiomyopathies are among the conditions that can arise from LMNA mutations. Besides gene mutations, altered posttranslational modifications (PTMs) of this protein can disrupt their maturation and function, interfere with cellular signaling, and destabilize nuclear architecture. Several PTMs of LMNA have been implicated in cardiac aging by causing cellular dysfunction, elevated production of reactive oxygen species, and weakening of muscle cells. In this short review, we summarize the various types of PTMs such as phosphorylation, acetylation, SUMOylation, farnesylation, and palmitoylation of LMNA and explained how their modification can contribute to cardiac ageing and related cardiovascular disorders.