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Proteolysis by both proteasomal and lysosomal pathways also tends to decline with aging and certain disease states, which may further contribute to cellular senescence and to pathologies characterized by protein deposition, such as atherosclerosis, cataract, macular degeneration, rheumatoid arthritis, and neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) (8, 11, 18, 33, 42)