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Clinical Trials Targeting Aging

The risk of morbidity and mortality increases exponentially with age. Chronic inflammation, accumulation of DNA damage, dysfunctional mitochondria, and increased senescent cell load are factors contributing to this. Mechanistic investigations have revealed specific pathways and processes which, prop...

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Autores principales: Nielsen, Johannes Leth, Bakula, Daniela, Scheibye-Knudsen, Morten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261384/
https://www.ncbi.nlm.nih.gov/pubmed/35821843
http://dx.doi.org/10.3389/fragi.2022.820215
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author Nielsen, Johannes Leth
Bakula, Daniela
Scheibye-Knudsen, Morten
author_facet Nielsen, Johannes Leth
Bakula, Daniela
Scheibye-Knudsen, Morten
author_sort Nielsen, Johannes Leth
collection PubMed
description The risk of morbidity and mortality increases exponentially with age. Chronic inflammation, accumulation of DNA damage, dysfunctional mitochondria, and increased senescent cell load are factors contributing to this. Mechanistic investigations have revealed specific pathways and processes which, proposedly, cause age-related phenotypes such as frailty, reduced physical resilience, and multi-morbidity. Among promising treatments alleviating the consequences of aging are caloric restriction and pharmacologically targeting longevity pathways such as the mechanistic target of rapamycin (mTOR), sirtuins, and anti-apoptotic pathways in senescent cells. Regulation of these pathways and processes has revealed significant health- and lifespan extending results in animal models. Nevertheless, it remains unclear if similar results translate to humans. A requirement of translation are the development of age- and morbidity associated biomarkers as longitudinal trials are difficult and not feasible, practical, nor ethical when human life span is the endpoint. Current biomarkers and the results of anti-aging intervention studies in humans will be covered within this paper. The future of clinical trials targeting aging may be phase 2 and 3 studies with larger populations if safety and tolerability of investigated medication continues not to be a hurdle for further investigations.
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spelling pubmed-92613842022-07-11 Clinical Trials Targeting Aging Nielsen, Johannes Leth Bakula, Daniela Scheibye-Knudsen, Morten Front Aging Aging The risk of morbidity and mortality increases exponentially with age. Chronic inflammation, accumulation of DNA damage, dysfunctional mitochondria, and increased senescent cell load are factors contributing to this. Mechanistic investigations have revealed specific pathways and processes which, proposedly, cause age-related phenotypes such as frailty, reduced physical resilience, and multi-morbidity. Among promising treatments alleviating the consequences of aging are caloric restriction and pharmacologically targeting longevity pathways such as the mechanistic target of rapamycin (mTOR), sirtuins, and anti-apoptotic pathways in senescent cells. Regulation of these pathways and processes has revealed significant health- and lifespan extending results in animal models. Nevertheless, it remains unclear if similar results translate to humans. A requirement of translation are the development of age- and morbidity associated biomarkers as longitudinal trials are difficult and not feasible, practical, nor ethical when human life span is the endpoint. Current biomarkers and the results of anti-aging intervention studies in humans will be covered within this paper. The future of clinical trials targeting aging may be phase 2 and 3 studies with larger populations if safety and tolerability of investigated medication continues not to be a hurdle for further investigations. Frontiers Media S.A. 2022-02-04 /pmc/articles/PMC9261384/ /pubmed/35821843 http://dx.doi.org/10.3389/fragi.2022.820215 Text en Copyright © 2022 Nielsen, Bakula and Scheibye-Knudsen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Aging
Nielsen, Johannes Leth
Bakula, Daniela
Scheibye-Knudsen, Morten
Clinical Trials Targeting Aging
title Clinical Trials Targeting Aging
title_full Clinical Trials Targeting Aging
title_fullStr Clinical Trials Targeting Aging
title_full_unstemmed Clinical Trials Targeting Aging
title_short Clinical Trials Targeting Aging
title_sort clinical trials targeting aging
topic Aging
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261384/
https://www.ncbi.nlm.nih.gov/pubmed/35821843
http://dx.doi.org/10.3389/fragi.2022.820215
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