Mechanisms and implications of sex differences in cardiac aging

Aging promotes structural and functional remodeling of the heart, even in the absence of external factors. There is growing clinical and experimental evidence supporting the existence of sex-specific patterns of cardiac aging, and in some cases, these sex differences emerge early in life. Despite efforts to identify sex-specific differences in cardiac aging, understanding how these differences are established and regulated remains limited. In addition to contributing to sex differences in age-related heart disease, sex differences also appear to underlie differential responses to cardiac stress such as adrenergic activation. Identifying the underlying mechanisms of sex-specific differences may facilitate the characterization of underlying heart disease phenotypes, with the ultimate goal of utilizing sex-specific therapeutic approaches for cardiac disease. The purpose of this review is to discuss the mechanisms and implications of sex-specific cardiac aging, how these changes render the heart more susceptible to disease, and how we can target age- and sex-specific differences to advance therapies for both male and female patients.