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Aging, frailty and complex networks

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Abstract

When people age their mortality rate increases exponentially, following Gompertz’s law. Even so, individuals do not die from old age. Instead, they accumulate age-related illnesses and conditions and so become increasingly vulnerable to death from various external and internal stressors. As a measure of such vulnerability, frailty can be quantified using the frailty index (FI). Larger values of the FI are strongly associated with mortality and other adverse health outcomes. This association, and the insensitivity of the FI to the particular health variables that are included in its construction, makes it a powerful, convenient, and increasingly popular integrative health measure. Still, little is known about why the FI works so well. Our group has recently developed a theoretical network model of health deficits to better understand how changes in health are captured by the FI. In our model, health-related variables are represented by the nodes of a complex network. The network has a scale-free shape or “topology”: a few nodes have many connections with other nodes, whereas most nodes have few connections. These nodes can be in two states, either damaged or undamaged. Transitions between damaged and non-damaged states are governed by the stochastic environment of individual nodes. Changes in the degree of damage of connected nodes change the local environment and make further damage more likely. Our model shows how age-dependent acceleration of the FI and of mortality emerges, even without specifying an age-damage relationship or any other time-dependent parameter. We have also used our model to assess how informative individual deficits are with respect to mortality. We find that the information is larger for nodes that are well connected than for nodes that are not. The model supports the idea that aging occurs as an emergent phenomenon, and not as a result of age-specific programming. Instead, aging reflects how damage propagates through a complex network of interconnected elements.

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Acknowledgements

The work was supported by the Nova Scotia Health Authority research fund (ABM), and by the Natural Sciences and Engineering Research Council of Canada (NSERC) with operating Grant RGPIN-2014-06245 (ADR) and with a CGSM fellowship (SF). KR is supported by the Dalhousie Medical Research Foundation as the Kathryn Allen Weldon Professor of Alzheimer Research.

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Authors and Affiliations

  1. Department of Medicine, Dalhousie University, Halifax, Canada

    A. B. Mitnitski & K. Rockwood

  2. Geriatric Medicine Research Unit, Halifax, Canada

    A. B. Mitnitski & K. Rockwood

  3. Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Canada

    A. D. Rutenberg & S. Farrell

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  1. A. B. Mitnitski
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  2. A. D. Rutenberg
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  3. S. Farrell
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  4. K. Rockwood
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ABM, ADR and KR conceived the study. SF carried out the coding, calculations, and figure preparation; this was done in close consultation with ADR. All authors contributed to, read, and approved the final manuscript.

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Correspondence to A. B. Mitnitski.

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Mitnitski, A.B., Rutenberg, A.D., Farrell, S. et al. Aging, frailty and complex networks. Biogerontology 18, 433–446 (2017). https://doi.org/10.1007/s10522-017-9684-x

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