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Review
. 2023 Oct;22(20):2324-2345.
doi: 10.1080/15384101.2023.2287929. Epub 2023 Dec 15.

Understanding cellular senescence: pathways involved, therapeutics and longevity aiding

Ashish Kumar  1 , Kavitha Thirumurugan  1
Affiliations
Review

Understanding cellular senescence: pathways involved, therapeutics and longevity aiding

Ashish Kumar et al. Cell Cycle. 2023 Oct.

Abstract

A normal somatic cell undergoes cycles of finite cellular divisions. The presence of surveillance checkpoints arrests cell division in response to stress inducers: oxidative stress from excess free radicals, oncogene-induced abnormalities, genotoxic stress, and telomere attrition. When facing such stress when undergoing these damages, there is a brief pause in the cell cycle to enable repair mechanisms. Also, the nature of stress determines whether the cell goes for repair or permanent arrest. As the cells experience transient or permanent stress, they subsequently choose the quiescence or senescence stage, respectively. Quiescence is an essential stage that allows the arrested/damaged cells to go through appropriate repair mechanisms and then revert to the mainstream cell cycle. However, senescent cells are irreversible and accumulate with age, resulting in inflammation and various age-related disorders. In this review, we focus on senescence-associated pathways and therapeutics understanding cellular senescence as a cascade that leads to aging, while discussing the recent details on the molecular pathways involved in regulating senescence and the benefits of therapeutic strategies against accumulated senescent cells and their secretions.

Keywords: DNA damage; SASP; Senescence; aging; longevity; senolytic.

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Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1.
Figure 1.
Cell cycle regulation of senescence. In response to chronic stress, cells arrest their replicative phase and promote cellular senescence to avoid multiplication of damaged or mutated genetic information and cellular aberrations. The process of cellular senescence is facilitated by cyclin dependent kinase inhibitors that help in arresting the cell cycle by repressing CDKs.
Figure 2.
Figure 2.
Secretion of senescence-associated secretory proteins. The SASP factors secreted from senescent cells influence their cellular environment. The secretions mostly consist of pro-inflammatory cytokines and chemokines e.g. IL-6, IL-8, NF-κB, etc. Over time, these secretions will cascade into auto-immune diseases and inflammation. Studies suggest inhibition of SASP proteins can help with age-related degeneracies.
Figure 3.
Figure 3.
Overall regulations during the cell cycle and role of dream complex. This figure encompasses the signal-mediated pathways which result in senescence. Various transcriptional factors cascade into triggering cellular senescence, such as p53/p21WAF1/CIP1 and p16INK4a/RB, retinoblastoma tumour-suppressing pathways. They play an important role in the regulation of the cell cycle and cell death.
Figure 4.
Figure 4.
Role of p53 in determining cellular arrest or proliferation.
See this image and copyright information in PMC

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