Abstract

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally among older adults. Similar to humans, age-related declines in cardiac function are observed in C57BL/6 mice. Angiotensin-converting enzyme 2 (ACE2), a key component of the renin–angiotensin system (RAS), counteracts detrimental RAS effects by converting angiotensin II (Ang II) to angiotensin-(1-7) (Ang-(1-7)), thereby playing a critical role in mitigating CVD pathogenesis. Here, we utilized transgenic K18-hACE2 mice to investigate the protective effects of ACE2 against cardiac aging. Histological and morphometric analyses revealed significant reductions in heart weight and improvements in cardiac structure in K18-hACE2 mice compared to wild-type controls. Furthermore, aged C57BL/6 mice exhibited progressive cardiac aging phenotypes, including mitochondrial dysfunction, telomere shortening, and immune dysregulation—all of which were significantly attenuated in K18-hACE2 mice. These findings demonstrate the protective role of ACE2 in cardiac aging and highlight its potential as a therapeutic target for anti-aging interventions.