Figure 2.

Decline in protein quality control in the aging heart. The heart exhibits a progressive decline in the intracellular protein quality control (PQC) pathways during the aging process. Macroautophagy, mitophagy and chaperone mediated autophagy (CMA) are lysosomal-dependent protein degradation pathways. Strong evidence exists that macroautophagy and mitophagy are decreased in old hearts. At present it is unclear how aging regulates CMA function in the heart. Enzymatic activities of the proteasome are severely reduced in the aging heart. As a consequence of impaired protein quality control, the aging heart accumulates misfolded protein aggregates (proteotoxicity), cell death proteins, and dysfunctional mitochondria. This cardio/proteo-toxic profile is associated with heightened fibrosis, collagen deposition, and cardiac hypertrophy.