Aging-related comorbidities, life-style interventions and therapeutic strategies in heart failure

Aging is a key risk factor for heart failure which significantly contributes to progressive structural and functional deteriorations in the heart, such as increased incidence of left ventricular hypertrophy, decline in left ventricle diastolic function, left atrial dilation, atrial fibrillation, myocardial fibrosis and cardiac amyloidosis, all contributing to compromised cardiac performance and leading to heart failure. Concurrently, aging-induced systemic changes in key organs, including liver, adipose tissue, kidneys, and skeletal muscles, further aggravate heart failure by disrupting endocrine signaling, energy balance and metabolic homeostasis. Aging-related comorbidities, including obesity, diabetes, coronary artery disease, atherosclerosis, hypertension and chronic kidney disease, also exacerbate the burden on failing heart through complex metabolic, inflammatory, and oxidative pathways. Lifestyle interventions, like dietary plans and physical activity, offer potential to counteract aging-related cardiovascular decline. Plant-based diets, calorie restriction and micronutrient supplementation are key dietary intervention to support cardiovascular health. Exercise mitigates oxidative stress and inflammation as well as promotes mitochondrial biogenesis and cardiac autophagy, improving overall heart function. Evolving therapeutic approaches, such as senolytics, senomorphics, sirtuin activators and anti-inflammatory agents, offer promising avenues to target senescent cells, enhance metabolic and mitochondrial efficiency and modulate inflammatory responses, thereby alleviating aging-related cardiac dysfunction. This review discusses the role of aging-related systemic decline and comorbidities in heart failure, highlighting the potential of integrative strategies combining lifestyle interventions and anti-aging therapies. Active translation of these strategies into clinics as targeted and personalized therapies offer potential to mitigate the global burden of aging-related heart failure and improve quality of life for aging populations.