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A complex systems approach to aging biology

Nature Aging volume 2, pages 580–591 (2022)Cite this article

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Abstract

Having made substantial progress understanding molecules, cells, genes and pathways, aging biology research is now moving toward integration of these parts, attempting to understand how their joint dynamics may contribute to aging. Such a shift of perspective requires the adoption of a formal complex systems framework, a transition being facilitated by large-scale data collection and new analytical tools. Here, we provide a theoretical framework to orient researchers around key concepts for this transition, notably emergence, interaction networks and resilience. Drawing on evolutionary theory, network theory and principles of homeostasis, we propose that organismal function is accomplished by the integration of regulatory mechanisms at multiple hierarchical scales, and that the disruption of this ensemble causes the phenotypic and functional manifestations of aging. We present key examples at scales ranging from sub-organismal biology to clinical geriatrics, outlining how this approach can potentially enrich our understanding of aging.

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Fig. 1: Shift to complex systems approaches in ecology and aging biology.
Fig. 2: Key examples of advances in aging biology using complex systems perspectives or methods.
Fig. 3: Multi-scale causality: the example of Alzheimer’s disease.
Fig. 4: Bowtie structure of aging pathways.

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Acknowledgements

We thank the International Conference on Complex Systems (2020) for sponsoring a workshop that led to this publication, under the guidance of E. Naumova. We thank J. Campisi and M. Kaeberlein for comments on the manuscript, and V. Legault for help creating figures. A.A.C. is a senior research scholar supported by the Fonds de recherche du Québec–Santé. This work was supported by the National Science and Engineering Research Council Grant nos. RGPIN-2018-06096 to A.A.C. and RGPIN-2019-05888 to A.R., Canadian Institutes of Health Research Grant no. 153011 to A.A.C., National Institutes of Health R01AG056440 to N.H., R01GM111458 to N.H. and R01AG068112 to N.H. M.G.M.O.R. is supported by research grants on complexity science for this work from the Dutch Research Council NWO (grants Compl21COV.001 and 645.003.002) and the Netherlands Organisation for Health Research and Development (ZonMw grant no 09120012010063). A.K. is supported by the Cell2Society Aging Research Network—A Drexel Research Excellence Initiative.

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Authors and Affiliations

  1. PRIMUS Research Group, Department of Family Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada

    Alan A. Cohen

  2. Research Center on Aging and Research Center of Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada

    Alan A. Cohen & Tamàs Fülöp

  3. Butler Columbia Aging Center and Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA

    Alan A. Cohen

  4. Intramural Research Program of the National Institute on Aging, Baltimore, MD, USA

    Luigi Ferrucci

  5. Department of Medicine, Geriatric Division, University of Sherbrooke, Sherbrooke, Quebec, Canada

    Tamàs Fülöp

  6. Department of Biology, University of Sherbrooke, Sherbrooke, Quebec, Canada

    Dominique Gravel

  7. Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, San Diego, CA, USA

    Nan Hao

  8. School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, USA

    Andres Kriete

  9. Department of Pathology, Yale School of Medicine, New Haven, CT, USA

    Morgan E. Levine

  10. Beth Israel Deaconess Medical Center, Hebrew SeniorLife, Hinda and Arthur Marcus Institute for Aging Research, and Harvard Medical School, Boston, MA, USA

    Lewis A. Lipsitz

  11. Department of Geriatrics, Radboud University Medical Centre, Nijmegen, the Netherlands

    Marcel G. M. Olde Rikkert

  12. Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia, Canada

    Andrew Rutenberg

  13. Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain

    Nicholas Stroustrup

  14. Universitat Pompeu Fabra (UPF), Barcelona, Spain

    Nicholas Stroustrup

  15. Department of Oncology, Quantitative Sciences Division, Johns Hopkins University, Baltimore, MD, USA

    Ravi Varadhan

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  1. Alan A. Cohen
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Contributions

This work emerged from a workshop on complex systems and aging organized by A.A.C. and in which all authors except D.G. participated. A.A.C. drafted the initial document and coordinated efforts. All authors contributed extensively to writing, editing and approving the final version.

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Correspondence to Alan A. Cohen.

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A.A.C. is CEO and founder at Oken Health.

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Nature Aging thanks Daniel Promislow and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Cohen, A.A., Ferrucci, L., Fülöp, T. et al. A complex systems approach to aging biology. Nat Aging 2, 580–591 (2022). https://doi.org/10.1038/s43587-022-00252-6

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