Aging is closely associated with a progressive decline in cardiovascular function, leading to higher risks of heart failure and reduced lifespan. Recent studies highlight the critical role of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr), a key enzyme in cholesterol biosynthesis, in modulating age-related cardiac changes. Dysregulation of Hmgcr activity during aging contributes to impaired lipid metabolism, oxidative stress, and mitochondrial dysfunction, all of which accelerate cardiac decline.
Exercise has emerged as one of the most effective non-pharmacological interventions to counter these effects. Regular physical activity improves cardiac output, reduces fibrosis, and enhances mitochondrial biogenesis in aged hearts. Importantly, exercise appears to regulate Hmgcr expression and activity, thereby restoring lipid homeostasis and reducing harmful cholesterol accumulation. By normalizing Hmgcr pathways, exercise not only improves cardiac metabolism but also mitigates inflammation and oxidative stress, key drivers of aging-related heart dysfunction.
Animal models and human studies consistently show that exercise-induced regulation of Hmgcr enhances cardiac resilience, delays the onset of cardiovascular disease, and extends lifespan. These findings underscore the therapeutic potential of lifestyle interventions. Targeting Hmgcr through exercise represents a promising strategy for preserving cardiac health and promoting healthy aging.