Regulation of Survival Networks in Senescent Cells: From Mechanisms to Interventions
Abel Soto-Gamez1, Wim J Quax2, Marco Demaria3
1Groningen Research Institute of Pharmacy, Chemical and Pharmaceutical Biology, University of Groningen, Groningen, the Netherlands; European Institute for the Biology of Aging (ERIBA), University Medical Center Groningen (UMCG), University of Groningen, Groningen, the Netherlands.
Abstract:
Cellular senescence is a state of stable cell cycle arrest arising in response to DNA and mitochondrial damages. Senescent cells undergo morphological, structural and functional changes that are influenced by a number of variables, including time, stress, tissue, and cell type. The heterogeneity of the senescent phenotype is exemplified by the many biological properties that senescent cells can cover. The advent of innovative model organisms has demonstrated a functional role of senescent cells during embryogenesis, tissue remodeling, tumorigenesis and aging. Importantly, prolonged and aberrant persistence of senescent cells is often associated with tissue dysfunction and pathology, and is partially the consequence of mechanisms that enhance survival and resistance to cell death. Here, we describe the main molecular players involved in promoting survival of senescent cells, with particular emphasis on the regulation of senescence-associated anti-apoptotic pathways. We discuss the consequences these pathways have in providing resistance to intrinsic and extrinsic pro-apoptotic signals. Finally, we highlight the importance of these pathways in the development of targets for senolytic interventions.
Insights
Cellular senescence involves cell cycle arrest due to damage. Senescent cells resist death through anti-apoptotic pathways, contributing to aging and disease, and are targets for senolytic therapies.
Area of Science:
- Cell Biology
- Molecular Biology
- Aging Research
Background:
- Cellular senescence is a stable cell cycle arrest triggered by DNA and mitochondrial damage.
- Senescent cells exhibit diverse phenotypes and play roles in development, tissue repair, and aging.
- Persistent senescent cells are linked to tissue dysfunction and pathology due to enhanced survival mechanisms.
Purpose of the Study:
- To describe molecular mechanisms promoting senescent cell survival.
- To emphasize the regulation of senescence-associated anti-apoptotic pathways.
- To highlight the role of these pathways in resistance to cell death and as targets for senolytic interventions.
Main Methods:
- Review of molecular players involved in senescent cell survival.
- Emphasis on the regulation of senescence-associated anti-apoptotic pathways.
- Discussion of resistance to intrinsic and extrinsic pro-apoptotic signals.
Main Results:
- Senescent cells employ specific molecular pathways to enhance survival.
- Anti-apoptotic pathways are crucial for resisting programmed cell death signals.
- These survival mechanisms contribute to the aberrant persistence of senescent cells.
Conclusions:
- Understanding senescent cell survival pathways is key to addressing age-related diseases.
- Targeting senescence-associated anti-apoptotic pathways offers a therapeutic strategy.
- Senolytic interventions hold promise for treating pathologies linked to persistent senescent cells.
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