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OtherReview Article

Cellular senescence: from mechanisms to current biomarkers and senotherapies

Vasco Lucas, Cláudia Cavadas and Célia Alexandra Aveleira
Pharmacological Reviews February 17, 2023, PHARMREV-AR-2022-000622; DOI: https://doi.org/10.1124/pharmrev.122.000622
Vasco Lucas
1Center for Neuroscience and Cell Biology, University of Coimbra, Portugal
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Cláudia Cavadas
1Center for Neuroscience and Cell Biology, University of Coimbra, Portugal
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Célia Alexandra Aveleira
1Center for Neuroscience and Cell Biology, University of Coimbra, Portugal
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  • ORCID record for Célia Alexandra Aveleira
  • For correspondence: celia.aveleira@uc.pt
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Abstract

An increase in life expectancy in developed countries has led to an insurgency of chronic aging-related diseases. In the last few decades, several studies provided evidence of the prominent role of cellular senescence in many of these pathologies. Key traits of senescent cells include cell cycle arrest, apoptosis resistance, and secretome shift to senescence-associated secretory phenotype (SASP) resulting in increased secretion of various intermediate bioactive factors important for senescence pathophysiology. However, cellular senescence is a highly phenotypically heterogeneous process, hindering the discovery of totally specific and accurate biomarkers. Also, strategies to prevent the pathological effect of senescent cell accumulation during aging by impairing senescence onset or promoting senescent cell clearance have shown great potential during in vivo studies and some are already in early stages of clinical translation. The adaptability of these senotherapeutic approaches to human application has been questioned due to the lack of proper senescence targeting and senescence involvement in important physiological functions. In this review, we explore the heterogeneous phenotype of senescent cells and its influence on the expression of biomarkers currently used for senescence detection. We also discuss the current evidence regarding the efficacy, reliability, development stage, and potential for human applicability of the main existing senotherapeutic strategies.

Significance Statement This manuscript is an extensive review of what is currently known about the complex process of cellular senescence exploring its most defining features. The main body of the discussion focus on how the multi-feature fluctuation of the senescence phenotype and the physiological role of cellular senescence have both caused a limitation in the search for truly reliable senescence biomarkers and the progression in the development of senotherapies.

  • aging
  • cell injury
  • clinical pharmacology
  • molecular drug targeting
  • signalling pathways
  • Structure/function/mechanism
  • Copyright © 2023 American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 75 (2)
Pharmacological Reviews
Vol. 75, Issue 2
1 Mar 2023
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OtherReview Article

The Quest to Define and Target Cellular Senescence

Vasco Lucas, Cláudia Cavadas and Célia Alexandra Aveleira
Pharmacological Reviews February 17, 2023, PHARMREV-AR-2022-000622; DOI: https://doi.org/10.1124/pharmrev.122.000622

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OtherReview Article

The Quest to Define and Target Cellular Senescence

Vasco Lucas, Cláudia Cavadas and Célia Alexandra Aveleira
Pharmacological Reviews February 17, 2023, PHARMREV-AR-2022-000622; DOI: https://doi.org/10.1124/pharmrev.122.000622
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