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A complex systems approach to aging biology
Open accessAbstract
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. The authors discuss how adopting a complex systems perspective is a crucial step in advancing our understanding of the aging process and requires fundamental alteration of the questions being asked and the methods used to answer them.
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“During ageing, adaptive responses are weakened due to deficits in the CAS network.83”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [83]
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“When a stimulus is too intense and exceeds the regulatory capacity of the adaptive response or when the compromised adaptive response is insufficient to recover from stimulus-induced perturbations, homoeostasis is disrupted, leading to the onset of disease.83–85”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [83]
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Metadata
- Authors
- 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., Stroustrup, N., & Varadhan, R.
- Affiliations
- Université de Sherbrooke (CA)
- National Institute on Aging (US)
- University of California San Diego (US)
- Drexel University (US)
- Yale University (US)
- Beth Israel Deaconess Medical Center (US)
- Dalhousie University (CA)
- Universitat Pompeu Fabra (ES)
- Johns Hopkins University (US)
- Corresponding author
- Cohen, Alan A.
- ORCID
- Venue
- Nature Aging
- Published
- 2022-07-20
- Volume
- 2
- Issue
- 7
- Pages
- 580-591
- ISSN
- 2662-8465 (ISSN-L)
- PMC
- PMC12007111
- OpenAlex
- W4286008101
- Cited by
- 221
- References
- 140
- Citations by year
- 2026: 53 · 2025: 61 · 2024: 60 · 2023: 44 · 2022: 3
- FWCI
- 3.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Aging (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Drexel University
- ZonMw (09120012010063)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (645.003.002, COMPL.21COV.001)
- National Institutes of Health
- Canadian Institutes of Health Research (153011)
- National Institute on Aging (R01AG056440, R01AG068112)
- National Institute of General Medical Sciences (R01GM111458)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Social Sciences › Arts and Humanities › History and Philosophy of Science › Philosophy of Biology and Scientific Explanation
- Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › Complex Systems and Dynamics
- Keywords
- biological aging, complex systems, emergence, interaction networks, resilience, homeostasis, hierarchical regulation, network theory, evolutionary theory, multiscale integration, geriatrics
- MeSH terms
- Biology, Geriatrics, Homeostasis, Systems Analysis
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