Abstract
Aging contributes significantly to the deterioration of cardiac function and increases the prevalence of heart failure, including those with reduced or preserved ejection fraction. Heart failure with preserved ejection fraction (HFpEF) is highly prevalent in the elderly population and it has become a leading cause of morbidity and mortality in this group. This commentary discusses the important findings and broader implications of the study by Daneshgar et al. on the role of the anti-aging hormone α-Klotho in alleviating diastolic dysfunction in the aged heart via Sirtuin1 (Sirt1)-mediated pathways. Using aged and Klothodeficient mouse models, they demonstrated that soluble Klotho (sKL) supplementation improved cardiac diastolic function, reduced left ventricular hypertrophy and fibrosis, and increased capillary density. Mechanistically, the cardioprotective effects of sKL were found to rely on Sirt1-mediated regulation of DNA damage pathways and cardiac protein acetylation. These findings provide new insights into the therapeutic potential of targeting the Klotho-Sirt1 axis for HFpEF and other age-related cardiovascular diseases.