Researchers here offer opinions reflective of the present research mainstream on which mechanisms are important in the aging of the heart and its consequent dysfunctions. This sort of article is an interesting measure of the degree to which the "aging is accumulated damage" viewpoint exemplified by the Strategies for Engineered Negligible Senescence (SENS) has won ground in the ongoing war of ideas regarding the matter of research strategy for the treatment of aging and age-related disease. For example: targeting senescent cells is now mainstream; mitochondrial dysfunction remains a topic in which everyone agrees there is a problem, but disagrees on the nature of that problem; and epigenetic change has been eagerly adopted as a point of intervention by a research community that was already spending much of its time on trying to adjust gene expression for therapeutic effect.
Cardiac aging is a fundamental driver of cardiovascular diseases (CVDs), the leading cause of global mortality. While age is a non-modifiable risk factor, understanding its underlying molecular basis offers new avenues for therapeutic intervention. This review synthesizes the key mechanisms driving cardiac aging and evaluates promising strategies to counteract them. Our aim is to provide a forward-looking perspective, arguing that a paradigm shift from single-target interventions to synergistic, systems-level approaches is necessary to promote healthy aging and longevity.
We delineate the hallmark structural and functional changes of the aging heart, including left ventricular hypertrophy, diastolic dysfunction, and increased fibrosis. We then explore the core molecular pathways, highlighting the critical roles of dysfunctional autophagy, mitochondrial oxidative stress, telomere shortening, and profound epigenetic shifts, particularly the dysregulation of non-coding RNAs such as miR-34a. Building on this mechanistic framework, we assess a range of interventions, from lifestyle modifications like caloric restriction to targeted pharmaceuticals including rapamycin and senolytics. Furthermore, we discuss the potential of next-generation therapies such as microbiome modulation, cell-based regeneration, and gene editing.
Link: https://doi.org/10.1016/j.phrs.2025.107954
View the full article at FightAging
