Aging, Cellular Senescence, and Alzheimer’s Disease

• Published in: International journal of molecular sciences Vol. 23; no. 4; p. 1989
• Main Author: Liu, Rui-Ming
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.02.2022; MDPI
• Subjects: Age; Aging; Aging - pathology; Alzheimer Disease - pathology; Alzheimer's disease; Animals; Apoptosis; Astrocytes - pathology; Brain - pathology; Cancer; Cell cycle; Cell growth; Cellular Senescence - physiology; Cyclin-dependent kinases; DNA damage; Humans; Hypotheses; Kinases; Musculoskeletal system; Neurons - pathology; Oxidative stress; Pathophysiology; Physiology; Proteins; Review; Rodents; Senescence; Stem cells; plasminogen activator inhibitor 1 (PAI-1); tauopathy; cellular senescence; Alzheimer’s disease; neurodegeneration; telomere shortening; aging; late-onset Alzheimer’s disease (LOAD); β-amyloid peptides (Aβ); oxidative stress
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23041989

Aging is the greatest risk factor for late-onset Alzheimer’s disease (LOAD), which accounts for >95% of Alzheimer’s disease (AD) cases. The mechanism underlying the aging-related susceptibility to LOAD is unknown. Cellular senescence, a state of permanent cell growth arrest, is believed to contribute importantly to aging and aging-related diseases, including AD. Senescent astrocytes, microglia, endothelial cells, and neurons have been detected in the brain of AD patients and AD animal models. Removing senescent cells genetically or pharmacologically ameliorates β-amyloid (Aβ) peptide and tau-protein-induced neuropathologies, and improves memory in AD model mice, suggesting a pivotal role of cellular senescence in AD pathophysiology. Nonetheless, although accumulated evidence supports the role of cellular senescence in aging and AD, the mechanisms that promote cell senescence and how senescent cells contribute to AD neuropathophysiology remain largely unknown. This review summarizes recent advances in this field. We believe that the removal of senescent cells represents a promising approach toward the effective treatment of aging-related diseases, such as AD.