Vinculin at the heart of aging

With age, the heart and large arteries show decreased elasticity. In arteries, this results in increased resistance to cardiac pump function and increased workload against this resistance results in pathological cardiac hypertrophy (1). The left ventricle undergoes an increase in wall thickness and an overall expansion of left ventricular mass with age. At the cellular level, this overload results in an increase in cardiomyocyte dimension and decrease in cardiomyocyte number (2). In terms of the cardiac scaffold, collagen deposition increases in the aging heart, contributing to further stiffening of the myocardium (2). These factors altogether impact diastolic function of the heart, impairing the ability for proper relaxation and ventricular filling. Systolic function is not often affected with cardiac aging, based on the preserved ejection fraction and stroke volume associated with heart failure (3). The cytoskeleton encompasses a network of proteins associated with the sarcomere (titin, α-actinin), true cytoskeleton (desmin, actin), cell membrane (vinculin, dystrophin), and intercalated disc (ICD) (desmoplakin, connexin 43) that function to provide cell stability, as well as transmit and receive mechanical and chemical stimuli both within and between cells (4). During cardiac stress and failure, there are significant alterations in the expression of cardiomyocyte cytoskeletal proteins, including myosin and vinculin (4). Cytoskeletal alterations are also observed during cardiac aging (5). However the consequences of these alterations in disease and aging on mechanosensing, force transmission, and global heart function remain unknown. In the recent publication, “Vinculin network-mediated cytoskeletal remodeling regulates contractile function in the aging heart”, Kaushik et al. identify a protective role for vinculin in the aging heart. Their study exploits proteomic analysis of simian and murine ventricles as well as functional analysis of transgenic Drosophila models to highlight a major role for vinculin-mediated cytoskeletal remodeling in mechanotransmission during cardiac aging (Figure 1).