Abstract
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.
Highlights
Cellular senescence, including replicative senescence (RS) and stress-induced premature senescence (SIPS), represents a state of permanent cell growth arrest [1–3]
Cellular senescence can occur at any life stage from embryo to adulthood, it is associated with the aging process [4–6]
Direct exposure of cultured oligodendrocyte precursor cells (OPCs) to aggregated Aβ induced senescence in these cells [25]. They showed that treatment of amyloid precursor protein (APP)/presenilin 1 (PS1) mice with senolytic drugs selectively removed senescent cells from the plaque environment, reduced neuroinflammation and Aβ load, and ameliorated memory deficits [25]
Summary
Cellular senescence, including replicative senescence (RS) and stress-induced premature senescence (SIPS), represents a state of permanent cell growth arrest [1–3]. Senescent cells display three major characteristics—loss of proliferation or regeneration capacity, alteration of metabolic functions and resistance to apoptosis, and secretion of an array of pathogenically active molecules, termed senescence-associated secretary phenotype (SASP) [1,16] (Figure 1). Increased expression of cell cycle repressors and SA-β-gal activity, as well as senescent morphological changes, can be revealed and correlated with cell cycle repression in replicative senescence (RS) or stress-induced premature senescence (SIPS) cells in culture. Oncogene activation, DNA damag perturbation, and stress, have been proposed [1] (Figure 1). It should be different factors may contribute to cell senescence under different patholog. Sci. 2022, 23, 1989 cells contribute to the pathogenesis of diseases may lead to the development of novel therapeutics for the treatment of these aging-related diseases
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