Cardiac Aging: From Basic Research to Therapeutics

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.