🔹Cardiac aging is a natural process characterized by cardiomyocyte hypertrophy and dysfunction.
🔹Energy Metabolism Transformation*
- decrease in the number and function of these cells, along with reduced energy transfer efficiency
- shift in energy metabolism substrates from fatty acids to glucose and ketone bodies
(mitochondrial dysfunction and decreased fatty acid oxidation)
🔹Changes in Enzyme Activity
- oxidative phosphorylation and ATP synthase activity in myocardial mitochondria decrease
- antioxidant enzymes like MnSOD also decreases, increasing sensitivity to oxidative stress and DNA damage
- AMPK, an enzyme regulating energy metabolism, shows decreased activity, impairing energy metabolism processes
🔹Gene Regulation and Metabolism
- changes in gene expression levels, affecting oxidative phosphorylation, substrate metabolism, and the tricarboxylic acid cycle
- ROS metabolism changes, enhancing ROS production in cardiomyocytes
- down-regulation of KDM6A and SIRT3 genes (demethylation and deacetylation respectively)
🔹Mitochondrial Dysfunction (producing about 95% of myocardial ATP)
- mitochondrial dysfunction, characterized by structural changes, reduced activity of respiratory chain complexes, and impaired energy transport pathways
🔹Hormonal Metabolism Changes
- reduced levels of ANP and altered glucocorticoid receptor expression
- Brain-derived neurotrophic factor (BDNF) levels decrease
🔹Impaired Autophagy
- accumulation of damaged mitochondria and increased ROS production
🔹Metabolomic Changes in Signaling Pathways
- SIRT1/PGC-1α and PI3K/AKT/FOXO pathways
Reduced SIRT1 expression
Activation of PI3K/AKT signaling inhibits FOXO transcriptional activity
Comentarios