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
- University of Toronto, Canada
- Harvard Medical School, United States
- Dalhousie University, Canada
Abstract
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 towards 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 can affect both damage and repair rates, and hence robustness and resilience, in age and sex-dependent manners.
Data availability
Source data files for all figures and summary statistics for all fitting parameters and diagnostics of the models are provided. Only pre-existing datasets were used in this study. Information about the datasets and data cleaning is in the methods section. Raw data for mouse dataset 3 are freely available from https://github.com/SinclairLab/frailty. Raw human data are available from https://www.elsa-project.ac.uk/accessing-elsa-data after registering. All code is available at https://github.com/Spencerfar/aging-damagerepair. Our code for cleaning these raw datasets is provided.
Article and author information
Author details
Andrew David Rutenberg
Funding
Natural Sciences and Engineering Research Council of Canada (RGPIN-2019-05888)
- Andrew David Rutenberg
Canadian Institutes of Health Research (PJT 155961)
- Susan E Howlett
Heart and Stroke Foundation of Canada (G-22-0031992)
- Susan E Howlett
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Farrell et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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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
eLife 11:e77632.
https://doi.org/10.7554/eLife.77632
