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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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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. |
format | Online Article Text |
id | pubmed-9725749 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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