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Senescence under appraisal: hopes and challenges revisited

In recent years, cellular senescence has become the focus of attention in multiple areas of biomedical research. Typically defined as an irreversible cell cycle arrest accompanied by increased cellular growth, metabolic activity and by a characteristic messaging secretome, cellular senescence can im...

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Autores principales: Davan-Wetton, Camilla S. A., Pessolano, Emanuela, Perretti, Mauro, Montero-Melendez, Trinidad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038995/
https://www.ncbi.nlm.nih.gov/pubmed/33439271
http://dx.doi.org/10.1007/s00018-020-03746-x
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author Davan-Wetton, Camilla S. A.
Pessolano, Emanuela
Perretti, Mauro
Montero-Melendez, Trinidad
author_facet Davan-Wetton, Camilla S. A.
Pessolano, Emanuela
Perretti, Mauro
Montero-Melendez, Trinidad
author_sort Davan-Wetton, Camilla S. A.
collection PubMed
description In recent years, cellular senescence has become the focus of attention in multiple areas of biomedical research. Typically defined as an irreversible cell cycle arrest accompanied by increased cellular growth, metabolic activity and by a characteristic messaging secretome, cellular senescence can impact on multiple physiological and pathological processes such as wound healing, fibrosis, cancer and ageing. These unjustly called ‘zombie cells’ are indeed a rich source of opportunities for innovative therapeutic development. In this review, we collate the current understanding of the process of cellular senescence and its two-faced nature, i.e. beneficial/detrimental, and reason this duality is linked to contextual aspects. We propose the senescence programme as an endogenous pro-resolving mechanism that may lead to sustained inflammation and damage when dysregulated or when senescent cells are not cleared efficiently. This pro-resolving model reconciles the paradoxical two faces of senescence by emphasising that it is the unsuccessful completion of the programme, and not senescence itself, what leads to pathology. Thus, pro-senescence therapies under the right context, may favour inflammation resolution. We also review the evidence for the multiple therapeutic approaches under development based on senescence, including its induction, prevention, clearance and the use of senolytic and senomorphic drugs. In particular, we highlight the importance of the immune system in the favourable outcome of senescence and the implications of an inefficient immune surveillance in completion of the senescent cycle. Finally, we identify and discuss a number of challenges and existing gaps to encourage and stimulate further research in this exciting and unravelled field, with the hope of promoting and accelerating the clinical success of senescence-based therapies.
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spelling pubmed-80389952021-04-27 Senescence under appraisal: hopes and challenges revisited Davan-Wetton, Camilla S. A. Pessolano, Emanuela Perretti, Mauro Montero-Melendez, Trinidad Cell Mol Life Sci Review In recent years, cellular senescence has become the focus of attention in multiple areas of biomedical research. Typically defined as an irreversible cell cycle arrest accompanied by increased cellular growth, metabolic activity and by a characteristic messaging secretome, cellular senescence can impact on multiple physiological and pathological processes such as wound healing, fibrosis, cancer and ageing. These unjustly called ‘zombie cells’ are indeed a rich source of opportunities for innovative therapeutic development. In this review, we collate the current understanding of the process of cellular senescence and its two-faced nature, i.e. beneficial/detrimental, and reason this duality is linked to contextual aspects. We propose the senescence programme as an endogenous pro-resolving mechanism that may lead to sustained inflammation and damage when dysregulated or when senescent cells are not cleared efficiently. This pro-resolving model reconciles the paradoxical two faces of senescence by emphasising that it is the unsuccessful completion of the programme, and not senescence itself, what leads to pathology. Thus, pro-senescence therapies under the right context, may favour inflammation resolution. We also review the evidence for the multiple therapeutic approaches under development based on senescence, including its induction, prevention, clearance and the use of senolytic and senomorphic drugs. In particular, we highlight the importance of the immune system in the favourable outcome of senescence and the implications of an inefficient immune surveillance in completion of the senescent cycle. Finally, we identify and discuss a number of challenges and existing gaps to encourage and stimulate further research in this exciting and unravelled field, with the hope of promoting and accelerating the clinical success of senescence-based therapies. Springer International Publishing 2021-01-13 2021 /pmc/articles/PMC8038995/ /pubmed/33439271 http://dx.doi.org/10.1007/s00018-020-03746-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review
Davan-Wetton, Camilla S. A.
Pessolano, Emanuela
Perretti, Mauro
Montero-Melendez, Trinidad
Senescence under appraisal: hopes and challenges revisited
title Senescence under appraisal: hopes and challenges revisited
title_full Senescence under appraisal: hopes and challenges revisited
title_fullStr Senescence under appraisal: hopes and challenges revisited
title_full_unstemmed Senescence under appraisal: hopes and challenges revisited
title_short Senescence under appraisal: hopes and challenges revisited
title_sort senescence under appraisal: hopes and challenges revisited
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038995/
https://www.ncbi.nlm.nih.gov/pubmed/33439271
http://dx.doi.org/10.1007/s00018-020-03746-x
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