Cellular senescence, a form of terminal cell cycle arrest, is as a key driver of organismal ageing and an important factor in age-related diseases. Insights into the senescent phenotype have led to the development of novel therapeutic strategies, collectively known as senotherapies, that aim to ameliorate the detrimental effects of senescent cell accumulation in tissues. The senotherapeutic field has rapidly evolved over the past decade, with clinical translation of the first drugs discovered currently underway. What began as the straightforward removal of senescent cells using repurposed compounds, which were given the name of senolytics, has grown into an expanding field that uses different state of the art approaches to achieve the goal of preventing the build-up of senescent cells in the body. Here, we summarize the emergence of a new generation of senotherapies, based on improving the efficacy and safety of the original senolytics by making them targeted, but also branching out into drugs that prevent senescence (senoblockers) or revert it (senoreversers).The use of nanotechnology, specific antibodies, cell-based approaches and restored immunosurveillance is likely to revolutionize the field of senotherapies in the near future, hopefully allowing it to realize its full clinical potential.
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Review Article|
June 28 2024
A second generation of senotherapies: the development of targeted senolytics, senoblockers and senoreversers for healthy ageing
Vinesh Dhokia;
Vinesh Dhokia
1Mechanisms of Cancer and Ageing Laboratory, Barcelona, Spain
2Department of Molecular and Cell Biology, University of Leicester, Leicester, U.K.
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Amal Albati;
Amal Albati
1Mechanisms of Cancer and Ageing Laboratory, Barcelona, Spain
2Department of Molecular and Cell Biology, University of Leicester, Leicester, U.K.
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Hannah Smith;
Hannah Smith
1Mechanisms of Cancer and Ageing Laboratory, Barcelona, Spain
2Department of Molecular and Cell Biology, University of Leicester, Leicester, U.K.
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Gethin Thomas;
Gethin Thomas
3The Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester, U.K.
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Salvador Macip
1Mechanisms of Cancer and Ageing Laboratory, Barcelona, Spain
2Department of Molecular and Cell Biology, University of Leicester, Leicester, U.K.
3The Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester, U.K.
4Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Spain
5FoodLab, Faculty of Health Sciences, Universitat Oberta de Catalunya, Barcelona, Spain
Correspondence: Salvador Macip (sm460@le.ac.uk)
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Publisher: Portland Press Ltd
Received:
April 03 2024
Revision Received:
June 04 2024
Accepted:
June 07 2024
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2024
Biochem Soc Trans (2024) BST20231066.
Article history
Received:
April 03 2024
Revision Received:
June 04 2024
Accepted:
June 07 2024
Citation
Vinesh Dhokia, Amal Albati, Hannah Smith, Gethin Thomas, Salvador Macip; A second generation of senotherapies: the development of targeted senolytics, senoblockers and senoreversers for healthy ageing. Biochem Soc Trans 2024; BST20231066. doi: https://doi.org/10.1042/BST20231066
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