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The Interplay Between Stress Related Genes and Its Role in Human Longevity: Insights for Translational Studies

Human lifespan is a multifactorial trait resulted from complicated interplay among many genetic and environmental factors. Despite substantial progress in clarifying many aspects of lifespan’ variability the mechanism of its multifactorial regulation remains unclear. In this paper we investigate the...

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Autores principales: Yashin, Anatoliy, Wu, Deqing, Arbeev, Konstantin, Bagley, Olivia, Akushevich, Igor, Yashkin, Arseniy, Duan, Matt, Ukraintseva, Svetlana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8680526/
http://dx.doi.org/10.1093/geroni/igab046.2519
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author Yashin, Anatoliy
Wu, Deqing
Arbeev, Konstantin
Bagley, Olivia
Akushevich, Igor
Yashkin, Arseniy
Duan, Matt
Ukraintseva, Svetlana
author_facet Yashin, Anatoliy
Wu, Deqing
Arbeev, Konstantin
Bagley, Olivia
Akushevich, Igor
Yashkin, Arseniy
Duan, Matt
Ukraintseva, Svetlana
author_sort Yashin, Anatoliy
collection PubMed
description Human lifespan is a multifactorial trait resulted from complicated interplay among many genetic and environmental factors. Despite substantial progress in clarifying many aspects of lifespan’ variability the mechanism of its multifactorial regulation remains unclear. In this paper we investigate the role of genes from integrated stress response (ISR) pathway in such regulation. Experimental studies showed that persistent cellular stress may result in cellular senescence (for proliferating cells), or in apoptosis (for post-mitotic cells) which may affect health and lifespan in laboratory animals. These studies also showed which ISR genes are likely to interplay to produce joint effects on these traits. Note that in humans, the interplay between these genes does not necessarily influence these traits. This is because biological mechanisms regulating these traits in laboratory animals and humans may differ. This means that, when possible, the experimentally detected connections promising for human applications, should be verified using available human data before their testing in expensive clinical trials. In this paper we used HRS data to test connection between SNPs from the EIF2AK4 gene that senses cellular stress signals and the DDIT3 gene from the apoptosis regulation part of the ISR. We found genome wide significant associations between interacting SNPs from these genes and longevity. This result shows that available human data may be successfully used for making important steps in translation of experimental research findings towards their application in humans. Following this strategy may increase efficiency of clinical trials aiming to find appropriate medications to promote human health and longevity.
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spelling pubmed-86805262021-12-17 The Interplay Between Stress Related Genes and Its Role in Human Longevity: Insights for Translational Studies Yashin, Anatoliy Wu, Deqing Arbeev, Konstantin Bagley, Olivia Akushevich, Igor Yashkin, Arseniy Duan, Matt Ukraintseva, Svetlana Innov Aging Abstracts Human lifespan is a multifactorial trait resulted from complicated interplay among many genetic and environmental factors. Despite substantial progress in clarifying many aspects of lifespan’ variability the mechanism of its multifactorial regulation remains unclear. In this paper we investigate the role of genes from integrated stress response (ISR) pathway in such regulation. Experimental studies showed that persistent cellular stress may result in cellular senescence (for proliferating cells), or in apoptosis (for post-mitotic cells) which may affect health and lifespan in laboratory animals. These studies also showed which ISR genes are likely to interplay to produce joint effects on these traits. Note that in humans, the interplay between these genes does not necessarily influence these traits. This is because biological mechanisms regulating these traits in laboratory animals and humans may differ. This means that, when possible, the experimentally detected connections promising for human applications, should be verified using available human data before their testing in expensive clinical trials. In this paper we used HRS data to test connection between SNPs from the EIF2AK4 gene that senses cellular stress signals and the DDIT3 gene from the apoptosis regulation part of the ISR. We found genome wide significant associations between interacting SNPs from these genes and longevity. This result shows that available human data may be successfully used for making important steps in translation of experimental research findings towards their application in humans. Following this strategy may increase efficiency of clinical trials aiming to find appropriate medications to promote human health and longevity. Oxford University Press 2021-12-17 /pmc/articles/PMC8680526/ http://dx.doi.org/10.1093/geroni/igab046.2519 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Abstracts
Yashin, Anatoliy
Wu, Deqing
Arbeev, Konstantin
Bagley, Olivia
Akushevich, Igor
Yashkin, Arseniy
Duan, Matt
Ukraintseva, Svetlana
The Interplay Between Stress Related Genes and Its Role in Human Longevity: Insights for Translational Studies
title The Interplay Between Stress Related Genes and Its Role in Human Longevity: Insights for Translational Studies
title_full The Interplay Between Stress Related Genes and Its Role in Human Longevity: Insights for Translational Studies
title_fullStr The Interplay Between Stress Related Genes and Its Role in Human Longevity: Insights for Translational Studies
title_full_unstemmed The Interplay Between Stress Related Genes and Its Role in Human Longevity: Insights for Translational Studies
title_short The Interplay Between Stress Related Genes and Its Role in Human Longevity: Insights for Translational Studies
title_sort interplay between stress related genes and its role in human longevity: insights for translational studies
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8680526/
http://dx.doi.org/10.1093/geroni/igab046.2519
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