Akademik Veri Yönetim Sistemi
BIOGERONTOLOGY, cilt.2, sa.2, ss.2-30, 2021 (SCI-Expanded)
Aging is a process which leads to gradual redox status deterioration at the subcellular level. Proteostasis is a dynamic event that regulates protein’s redox status within the aging process to maintain redox stability of proteome. Proteostasis also includes the highly complex redox regulatory signaling pathways that affect various functions in the aging cell. At the subcellular level, other cellular organelles besides mitochondria, such as lysosomes, peroxisomes, and endoplasmic reticulum (ER), also produce reactive oxygen species (ROS) that contribute to proteomic aging. The optimum stability and function of proteome may be deteriorated by many aging-related factors such as impaired cellular redoxtasis, nonenzymatic post-translational modifications, and ER stress. Misfolded protein accumulation in the ER lumen interferes signal transduction-related events. Proteasome-autophagy systems possess the removal activity for oxidatively modified proteins and aging organelles. The ubiquitin–proteasome system is major intracellular protein degradation system that controls the garbage recycle process in the aging proteome. Aging-related impaired redoxtasis may cause nonenzymatic post-translational modification- related proteinopathies. The gradual accumulation of oxidatively modified and misfolded protein aggregates is the main characteristics of proteinopathies. Aging-induced interorganellar redox imbalance, impaired oxidative garbage removal, and deposition of modified proteins like amyloid β, tau proteins, α-synuclein, and amyloid polypeptides are all related to age-related protein misfolding diseases. Thus, in the long term, novel antiaging and senolytic strategies to restore proteostasis in aging proteome may provide an effective way to establish promising therapies for Alzheimer’s disease and other aging-induced protein misfolding diseases.