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Contextual modifiers of healthspan, lifespan, and epigenome in mice under chronic social stress

Sustained life stress and low socioeconomic status are among the major causes of aging-related diseases and decreased life expectancy. Experimental rodent models can help to identify the underlying mechanisms, yet very few studies address the long-term consequences of social stress on aging. We cond...

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Autores principales: Razzoli, Maria, Nyuyki-Dufe, Kewir, Chen, Brian H., Bartolomucci, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120026/
https://www.ncbi.nlm.nih.gov/pubmed/37043532
http://dx.doi.org/10.1073/pnas.2211755120
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author Razzoli, Maria
Nyuyki-Dufe, Kewir
Chen, Brian H.
Bartolomucci, Alessandro
author_facet Razzoli, Maria
Nyuyki-Dufe, Kewir
Chen, Brian H.
Bartolomucci, Alessandro
author_sort Razzoli, Maria
collection PubMed
description Sustained life stress and low socioeconomic status are among the major causes of aging-related diseases and decreased life expectancy. Experimental rodent models can help to identify the underlying mechanisms, yet very few studies address the long-term consequences of social stress on aging. We conducted a randomized study involving more than 300 male mice of commonly used laboratory strains (C57BL/6J, CD1, and Sv129Ev) chosen for the spontaneous aggression gradient and stress-vulnerability. Mice were exposed to a lifelong chronic psychosocial stress protocol to model social gradients in aging and disease vulnerability. Low social rank, inferred based on a discretized aggression index, was found to negatively impact lifespan in our study population. However, social rank interacted with genetic background in that low-ranking C57BL/6J, high-ranking Sv129Ev, and middle-ranking CD1 mice had lower survival, respectively, implying a cost of maintaining a given social rank that varies across strains. Machine learning linear discriminant analysis identified baseline fat-free mass as the most important predictor of mouse genetic background and social rank in the present dataset. Finally, strain and social rank differences were significantly associated with epigenetic changes, most significantly in Sv129Ev mice and in high-ranking compared to lower ranking subjects. Overall, we identified genetic background and social rank as critical contextual modifiers of aging and lifespan in an ethologically relevant rodent model of social stress, thereby providing a preclinical experimental paradigm to study the impact of social determinants of health disparities and accelerated aging.
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spelling pubmed-101200262023-10-12 Contextual modifiers of healthspan, lifespan, and epigenome in mice under chronic social stress Razzoli, Maria Nyuyki-Dufe, Kewir Chen, Brian H. Bartolomucci, Alessandro Proc Natl Acad Sci U S A Biological Sciences Sustained life stress and low socioeconomic status are among the major causes of aging-related diseases and decreased life expectancy. Experimental rodent models can help to identify the underlying mechanisms, yet very few studies address the long-term consequences of social stress on aging. We conducted a randomized study involving more than 300 male mice of commonly used laboratory strains (C57BL/6J, CD1, and Sv129Ev) chosen for the spontaneous aggression gradient and stress-vulnerability. Mice were exposed to a lifelong chronic psychosocial stress protocol to model social gradients in aging and disease vulnerability. Low social rank, inferred based on a discretized aggression index, was found to negatively impact lifespan in our study population. However, social rank interacted with genetic background in that low-ranking C57BL/6J, high-ranking Sv129Ev, and middle-ranking CD1 mice had lower survival, respectively, implying a cost of maintaining a given social rank that varies across strains. Machine learning linear discriminant analysis identified baseline fat-free mass as the most important predictor of mouse genetic background and social rank in the present dataset. Finally, strain and social rank differences were significantly associated with epigenetic changes, most significantly in Sv129Ev mice and in high-ranking compared to lower ranking subjects. Overall, we identified genetic background and social rank as critical contextual modifiers of aging and lifespan in an ethologically relevant rodent model of social stress, thereby providing a preclinical experimental paradigm to study the impact of social determinants of health disparities and accelerated aging. National Academy of Sciences 2023-04-12 2023-04-18 /pmc/articles/PMC10120026/ /pubmed/37043532 http://dx.doi.org/10.1073/pnas.2211755120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Razzoli, Maria
Nyuyki-Dufe, Kewir
Chen, Brian H.
Bartolomucci, Alessandro
Contextual modifiers of healthspan, lifespan, and epigenome in mice under chronic social stress
title Contextual modifiers of healthspan, lifespan, and epigenome in mice under chronic social stress
title_full Contextual modifiers of healthspan, lifespan, and epigenome in mice under chronic social stress
title_fullStr Contextual modifiers of healthspan, lifespan, and epigenome in mice under chronic social stress
title_full_unstemmed Contextual modifiers of healthspan, lifespan, and epigenome in mice under chronic social stress
title_short Contextual modifiers of healthspan, lifespan, and epigenome in mice under chronic social stress
title_sort contextual modifiers of healthspan, lifespan, and epigenome in mice under chronic social stress
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120026/
https://www.ncbi.nlm.nih.gov/pubmed/37043532
http://dx.doi.org/10.1073/pnas.2211755120
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