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Measurements of damage and repair of binary health attributes in aging mice and humans reveal that robustness and resilience decrease with age, operate over broad timescales, and are affected differently by interventions

As an organism ages, its health-state is determined by a balance between the processes of damage and repair. Measuring these processes requires longitudinal data. We extract damage and repair transition rates from repeated observations of binary health attributes in mice and humans to explore robust...

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Autores principales: Farrell, Spencer, Kane, Alice E, Bisset, Elise, Howlett, Susan E, Rutenberg, Andrew D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9725749/
https://www.ncbi.nlm.nih.gov/pubmed/36409200
http://dx.doi.org/10.7554/eLife.77632
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author Farrell, Spencer
Kane, Alice E
Bisset, Elise
Howlett, Susan E
Rutenberg, Andrew D
author_facet Farrell, Spencer
Kane, Alice E
Bisset, Elise
Howlett, Susan E
Rutenberg, Andrew D
author_sort Farrell, Spencer
collection PubMed
description As an organism ages, its health-state is determined by a balance between the processes of damage and repair. Measuring these processes requires longitudinal data. We extract damage and repair transition rates from repeated observations of binary health attributes in mice and humans to explore robustness and resilience, which respectively represent resisting or recovering from damage. We assess differences in robustness and resilience using changes in damage rates and repair rates of binary health attributes. We find a conserved decline with age in robustness and resilience in mice and humans, implying that both contribute to worsening aging health – as assessed by the frailty index (FI). A decline in robustness, however, has a greater effect than a decline in resilience on the accelerated increase of the FI with age, and a greater association with reduced survival. We also find that deficits are damaged and repaired over a wide range of timescales ranging from the shortest measurement scales toward organismal lifetime timescales. We explore the effect of systemic interventions that have been shown to improve health, including the angiotensin-converting enzyme inhibitor enalapril and voluntary exercise for mice. We have also explored the correlations with household wealth for humans. We find that these interventions and factors affect both damage and repair rates, and hence robustness and resilience, in age and sex-dependent manners.
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spelling pubmed-97257492022-12-07 Measurements of damage and repair of binary health attributes in aging mice and humans reveal that robustness and resilience decrease with age, operate over broad timescales, and are affected differently by interventions Farrell, Spencer Kane, Alice E Bisset, Elise Howlett, Susan E Rutenberg, Andrew D eLife Computational and Systems Biology As an organism ages, its health-state is determined by a balance between the processes of damage and repair. Measuring these processes requires longitudinal data. We extract damage and repair transition rates from repeated observations of binary health attributes in mice and humans to explore robustness and resilience, which respectively represent resisting or recovering from damage. We assess differences in robustness and resilience using changes in damage rates and repair rates of binary health attributes. We find a conserved decline with age in robustness and resilience in mice and humans, implying that both contribute to worsening aging health – as assessed by the frailty index (FI). A decline in robustness, however, has a greater effect than a decline in resilience on the accelerated increase of the FI with age, and a greater association with reduced survival. We also find that deficits are damaged and repaired over a wide range of timescales ranging from the shortest measurement scales toward organismal lifetime timescales. We explore the effect of systemic interventions that have been shown to improve health, including the angiotensin-converting enzyme inhibitor enalapril and voluntary exercise for mice. We have also explored the correlations with household wealth for humans. We find that these interventions and factors affect both damage and repair rates, and hence robustness and resilience, in age and sex-dependent manners. eLife Sciences Publications, Ltd 2022-11-21 /pmc/articles/PMC9725749/ /pubmed/36409200 http://dx.doi.org/10.7554/eLife.77632 Text en © 2022, Farrell et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Computational and Systems Biology
Farrell, Spencer
Kane, Alice E
Bisset, Elise
Howlett, Susan E
Rutenberg, Andrew D
Measurements of damage and repair of binary health attributes in aging mice and humans reveal that robustness and resilience decrease with age, operate over broad timescales, and are affected differently by interventions
title Measurements of damage and repair of binary health attributes in aging mice and humans reveal that robustness and resilience decrease with age, operate over broad timescales, and are affected differently by interventions
title_full Measurements of damage and repair of binary health attributes in aging mice and humans reveal that robustness and resilience decrease with age, operate over broad timescales, and are affected differently by interventions
title_fullStr Measurements of damage and repair of binary health attributes in aging mice and humans reveal that robustness and resilience decrease with age, operate over broad timescales, and are affected differently by interventions
title_full_unstemmed Measurements of damage and repair of binary health attributes in aging mice and humans reveal that robustness and resilience decrease with age, operate over broad timescales, and are affected differently by interventions
title_short Measurements of damage and repair of binary health attributes in aging mice and humans reveal that robustness and resilience decrease with age, operate over broad timescales, and are affected differently by interventions
title_sort measurements of damage and repair of binary health attributes in aging mice and humans reveal that robustness and resilience decrease with age, operate over broad timescales, and are affected differently by interventions
topic Computational and Systems Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9725749/
https://www.ncbi.nlm.nih.gov/pubmed/36409200
http://dx.doi.org/10.7554/eLife.77632
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