Senescent cells serve a useful function in younger life when they emerge transiently in response to injury and forms of cell stress and damage. Such cells are rapidly cleared by programmed cell death or by the immune system. Unfortunately the aging of the immune system and rising levels of cell and tissue damage ensures that senescent cells accumulate with age to disrupt tissue structure and function with their inflammatory secretions. Based on animal study evidence, this appears to be an important contribution to degenerative aging. In mice, clearing senescent cells produces rapid rejuvenation of many aspects of aging and reversal of many forms of age-related disease.
Cellular senescence occurs at all stages of life and is an important physiological mechanism of tissue remodeling during embryogenesis, antitumor protection, and wound healing. At the same time, increasing numbers of senescent cells in tissues is associated with aging of the organism, and senescence is also a pivotal determinant in the development and progression of chronic age-related diseases. Macromolecular damage accumulating in senescent cells leads to dysfunction of organelles, disruption of the secretory activity of the cell with the development of the senescence-associated secretory phenotype (SASP), and structural changes in cells. In turn, SASP factors induce the senescence of microenvironmental cells through paracrine and endocrine pathways.
Since it is well-known that the accumulation of senescent cells is associated with aging and the development of age-associated diseases, targeting of senescent cells is now considered as the most promising strategy for longlife intervention. Geroprotective preparations are represented by small-molecule compounds exhibiting cytotoxicity toward senescent cells (senolytics) and therapeutics inhibiting oxidative stress and harmful effects of SASP (senomorphics). Novel anti-aging approaches include immunotherapy directed at surface antigens specifically upregulated in senescent cells; in particular, chimeric antigen receptor (CAR) therapies and senolytic vaccines.
Senescent cells exhibit considerable heterogeneity, which complicates the development and implementation of geroprotective therapy. The hallmarks of senescent cells depend on tissue type and the phenotype of senescent cells. However, among the variety of bioactive substances, signaling pathways, and structural rearrangements associated with cellular aging, it is difficult to identify a universal marker of senescent cells. Given the complexity of detecting senescent cells, further studies should be conducted to reveal features of cellular aging using modern methods based on omics technologies with bioinformatics data analysis to develop relevant models for the assessment of cellular senescence.
Link: https://doi.org/10.3390/ijms26115390
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