Autophagy facilitates age-related cell apoptosis—a new insight from senile cataract

• Published in: Cell death & disease Vol. 13; no. 1; p. 37
• Main Authors: Huang, Jiani, Yu, Wangshu, He, Qin, He, Xiaoying, Yang, Ming, Chen, Wei, Han, Wei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.01.2022; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/2; 13/31; 13/89; 13/95; 14/19; 14/28; 38/91; 631/80/39/2346; 631/80/509; 631/80/82/23; 64/60; 692/699; 82/1; 82/80; Adaptor proteins; Adenine - analogs & derivatives; Adenine - pharmacology; Adult; Age; Aged; Aging - metabolism; Aging - pathology; Antibodies; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Autophagy; Autophagy - drug effects; Autophagy - physiology; Biochemistry; Biomedical and Life Sciences; Cataract - metabolism; Cataract - pathology; Cataracts; Cell Biology; Cell Culture; Cell death; Cell Survival; Cells, Cultured; Cellular Senescence - drug effects; Cellular Senescence - physiology; Epithelial cells; Humans; Immunology; Lens, Crystalline - metabolism; Lens, Crystalline - pathology; Life Sciences; Middle Aged; NF-kappa B - metabolism; NF-κB protein; Oxidative stress; Oxidative Stress - drug effects; p62 Protein; Protein kinase C; Senescence; Sequestosome-1 Protein - metabolism; Signal Transduction; Young Adult
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-04489-8

Age-related cell loss underpins many senescence-associated diseases. Apoptosis of lens epithelial cells (LECs) is the important cellular basis of senile cataract resulted from prolonged exposure to oxidative stress, although the specific mechanisms remain elusive. Our data indicated the concomitance of high autophagy activity, low SQSTM1/p62 protein level and apoptosis in the same LEC from senile cataract patients. Meanwhile, in primary cultured LECs model, more durable autophagy activation and more obvious p62 degradation under oxidative stress were observed in LECs from elder healthy donors, compared with that from young healthy donors. Using autophagy-deficiency HLE-B3 cell line, autophagy adaptor p62 was identified as the critical scaffold protein sustaining the pro-survival signaling PKCι-IKK-NF-κB cascades, which antagonized the pro-apoptotic signaling. Moreover, the pharmacological inhibitor of autophagy, 3-MA, significantly inhibited p62 degradation and rescued oxidative stress-induced apoptosis in elder LECs. Collectively, this study demonstrated that durable activation of autophagy promoted age-related cell death in LECs. Our work contributes to better understanding the pathogenesis of senescence-associated diseases.