Abstract
Senescent cells are generally characterized by permanent cell cycle arrest, metabolic alteration and activation, and apoptotic resistance in multiple organs due to various stressors. Excessive accumulation of senescent cells in numerous tissues leads to multiple chronic diseases, tissue dysfunction, age-related diseases and organ ageing. Immune cells can remove senescent cells. Immunaging or impaired innate and adaptive immune responses by senescent cells result in persistent accumulation of various senescent cells. Although senolytics—drugs that selectively remove senescent cells by inducing their apoptosis—are recent hot topics and are making significant research progress, senescence immunotherapies using immune cell-mediated clearance of senescent cells are emerging and promising strategies to fight ageing and multiple chronic diseases. This short review provides an overview of the research progress to date concerning senescent cell-caused chronic diseases and tissue ageing, as well as the regulation of senescence by small-molecule drugs in clinical trials and different roles and regulation of immune cells in the elimination of senescent cells. Mounting evidence indicates that immunotherapy targeting senescent cells combats ageing and chronic diseases and subsequently extends the healthy lifespan.
Highlights
Cellular senescence is a cell state in which the cell-cycle is generally irreversibly stopped [1], with cell-cycle reentry being a plausible scenario under specific circumstances, in tumor cells [2]
This review summarizes and discusses the latest advances concerning the different tissue-ageing and chronic diseases caused by different senescent cells, anti-ageing and chronic diseases by small-molecule drugs in clinical trials and distinct eradication of senescent cells by individual immune cells
Significantly improves the physical function of participants with idiopathic pulmonary fibrosis [45]. These results suggest that the strategy of combining treatments targeting different senescent cell populations with distinct phenotypes would be valid for anti-ageing and chronic diseases
Summary
Cellular senescence is a cell state in which the cell-cycle is generally irreversibly stopped [1], with cell-cycle reentry being a plausible scenario under specific circumstances, in tumor cells [2]. Cellular senescence is different from cell terminal differentiation accompanied by generally irreversible cell cycle arrest but without macromolecular damage [1]. There are two major types of cellular senescence: stress-induced premature cellular senescence [3] and replicative senescence due to a repeated cell cycle, which is usually mediated by telomere shortening [4]. Excessive accumulation of senescent cells causally shortens the healthy lifespan [11] and drives organ ageing [12], age-related organ deterioration/disorders [13,14], tissue dysfunction and chronic diseases, including cardiovascular diseases (CVDs) [15,16], cancer [2], neurodegenerative diseases [17,18]. Cellular senescence accumulation usually arises from increased stresses-induced cellular senescence and reduction of senescent cell removal due to apoptosis evasion and/or immune system dysfunction. This review summarizes and discusses the latest advances concerning the different tissue-ageing and chronic diseases caused by different senescent cells, anti-ageing and chronic diseases by small-molecule drugs in clinical trials and distinct eradication of senescent cells by individual immune cells
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