Cardiac Aging: From Basic Research to Therapeutics

Figures

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  Figure 1. Key mechanisms of cardiac aging. Abnormal expression of ncRNAs can cause dysregulation of their downstream target genes, which cause telomere damage and cardiac aging. MtDNA mutations, mitochondrial protein oxidation, and impaired mitochondrial turnover can cause the loss of mitochondrial function and lead to inadequate ATP synthesis and increased ROS production. Increased ROS can lead to further mitochondrial dysfunction, forming a vicious cycle. Elevated ROS also lead to telomere dysfunction, DNA damage, and autophagy. Wisper indicates Wisp2 super-enhancer–associated RNA; Meg3: maternally expressed gene 3; TERRA: telomeric repeat-containing RNA; TAF: telomere-associated DNA damage foci; mtDNA: mitochondrial DNA; ROS: reactive oxygen species; and SASP: senescence-associated secretory phenotype.

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  Figure 2. The concept of cardiac aging and its biological mechanism. Cardiac aging is a pathophysiological process affected by many factors triggered under various intrinsic and external stimuli with age. Many factors can affect key cellular processes and pathways during cardiac aging, such as oxidative stress, mitochondrial dysfunction, impaired autophagy, telomere damage, ncRNAs, and dysregulation of mTOR signaling. These factors can also influence each other and lead to cardiomyocyte senescence, apoptosis, and other cell damages. Cardiac aging causes changes in heart structure and function, such as progressive myocardial remodeling, decreases in systolic and diastolic function. CM indicates cardiomyocytes.