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Interpretable machine learning for high-dimensional trajectories of aging health
Abstract
We have built a computational model for individual aging trajectories of health and survival, which contains physical, functional, and biological variables, and is conditioned on demographic, lifestyle, and medical background information. We combine techniques of modern machine learning with an interpretable interaction network, where health variables are coupled by explicit pair-wise interactions within a stochastic dynamical system. Our dynamic joint interpretable network (DJIN) model is scalable to large longitudinal data sets, is predictive of individual high-dimensional health trajectories and survival from baseline health states, and infers an interpretable network of directed interactions between the health variables. The network identifies plausible physiological connections between health variables as well as clusters of strongly connected health variables. We use English Longitudinal Study of Aging (ELSA) data to train our model and show that it performs better than multiple dedicated linear models for health outcomes and survival. We compare our model with flexible lower-dimensional latent-space models to explore the dimensionality required to accurately model aging health outcomes. Our DJIN model can be used to generate synthetic individuals that age realistically, to impute missing data, and to simulate future aging outcomes given arbitrary initial health states.
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A one-dimensional representation of the complex biochemistry and phenotypes of aging is supported by analyses of aging data.
“The possibility of such a one-dimensional representation of the complex biochemistry and phenotypes of aging21–25 is supported by analyses of aging data26–30.”
From A damage accumulation model identifies distinct aging regimes across species (2026) · cites this paper as [28]
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Self-citationStochastic and genetic factors influence tissue-specific decline in ageing C. elegans
Herndon, L. A., Schmeissner, P. J., Dudaronek, J. M., Brown, P. A., Listner, K. M., Sakano, Y., Paupard, M. C., Hall, D. H., & Driscoll, M. (2002) · Nature · doi:10.1038/nature01135 · Cited by 1,214
Personal aging markers and ageotypes revealed by deep longitudinal profiling
Ahadi, S., Zhou, W., Schüssler-Fiorenza Rose, S. M., Sailani, M. R., Contrepois, K., Avina, M., Ashland, M., Brunet, A., & Snyder, M. (2020) · Nature Medicine · doi:10.1038/s41591-019-0719-5 · Cited by 408
Machine learning for comprehensive forecasting of Alzheimer’s Disease progression
Fisher, C. K., Smith, A. M., Walsh, J. R., Diseases, C. A. M., Simon, A. J., Edgar, C., Jack, C. R., Holtzman, D., Russell, D., Hill, D., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-49656-2 · Cited by 223
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A complex systems approach to aging biology
Cohen, A. A., Ferrucci, L., Fülöp, T., Gravel, D., Hao, N., Kriete, A., Levine, M. E., Lipsitz, L. A., Olde Rikkert, M. G. M., Rutenberg, A., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00252-6 · Cited by 221
Self-citationA damage accumulation model identifies distinct aging regimes across species
Raz, N., Yang, Y., Pridham, G., Shenhar, B., Frenkel, S., Levy, T., Tlusty, T., Mayo, A., & Alon, U. (2026) · Nature Aging · doi:10.1038/s43587-026-01138-7 · Cited by 7
Metadata
- Authors
- Farrell, S., Mitnitski, A., Rockwood, K., & Rutenberg, A. D.
- Venue
- PLOS Computational Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2022-01-10
- Volume
- 18
- Issue
- 1
- Pages
- e1009746
- ISSN
- 1553-7358
- PMC
- PMC8782527
- Cited by
- 22
- References
- 6
- Language
- en
- Update notices
- new_version (2022-01-21)
- Funders
- Natural Sciences and Engineering Research Council of Canada (RGPIN 2019-05888)
- Canadian Institutes of Health Research (PJT-156114)
- Dalhousie Medical Research Foundation
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