What defines a senescent cell?
Senescence is a cellular response characterized by a stable and long-term loss of growth potential and other phenotypic alterations, particularly the development of a proinflammatory secretome.
Hayflick first reported the limit of proliferation and division of human fibroblasts cultured in vitro [1], that is the Hayflick limit (Figure 1), which first drew attention to the limit of cell lifespan. This discovery aroused the enthusiasm of researchers to explore the mystery of life and new strategies for anti-aging. Since then, more and more research has been conducted on cellular senescence.
Figure 1. (a) Young and (b) old human diploid cells [2].
With the deepening of research, we have become increasingly aware of the dual role of cell senescence [3] (Figure 2):
On the one hand, the process of cell senescence plays an important role in the process of embryonic development, and can protect young organisms from carcinogenetic events, senescent cells can also be observed transiently at sites of tissue damage where they participate in tissue repair, wound healing and regeneration.
On the other hand, with age, senescent cells continue to accumulate in various tissues and secrete a large number of factors, these senescence-associated secretory phenotype (SASP) will recruit inflammatory cells, reshape the extracellular matrix, cause unnecessary cell death, induce fibrosis and inhibit stem cell function. In addition, SASP will also accelerate the aging of nearby-normal cells, and eventually lead to the function of various tissues being damaged, and the body’s function gradually declines [4,5].
Figure 2. Causes and consequences of cellular senescence.
Although senescent cells have certain benefits, their harmful effects far outweigh the benefits. They exist in various organs and systems, acting as the "wirepuller" behind various diseases and even leading to death (Figure 3). The study showed that transplantation of senescent cells into young mice was sufficient to drive age-related pathology and cause persistent physical dysfunction [6]. In contrast, the deletion of senescent cells by a genetic approach attenuated age-related deterioration and extended the healthspan in aged mice [7,8]. These studies suggested that humans may benefit from removing senescent cells.
Figure 3. Senescent Cells Play a Role in Age-Associated Diseases [4].
Abbreviations: AF, annulus fibrosus cells; NP, nucleus pulposus cells; RPE, retinal pigment epithelium.
Indeed, as expected, Senolysis in mouse models of diseases has been shown to improve atherosclerosis, osteoarthritis, cataracts, cardiac hypertrophy, renal dysfunction, lipodystrophy, and sarcopenia, as well as extend the average and healthy life span in mice [9]. Nowadays, more and more Senolytics are being discovered and concerned by people (Table 1), and we look forward to the day when Senolytics will truly benefit mankind.
Table 1. List of Completed, Ongoing, and Planned Clinical Trials with Senolytic.
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