Probing the network structure of health deficits in human aging

@article{Farrell2018ProbingTN,
  title={Probing the network structure of health deficits in human aging},
  author={Spencer G. Farrell and Arnold Mitnitski and Olga Theou and Kenneth Rockwood and Andrew D. Rutenberg},
  journal={bioRxiv},
  year={2018}
}
Human aging leads to the stochastic accumulation of damage. We model an aging population using a stochastic network model. Individuals are modeled as a network of interacting nodes, representing health attributes. Nodes in the network stochastically damage and repair, with rates dependent on the state of their neighbors. Damaged nodes represent health deficits. The Frailty Index (FI) assesses age-related damage as the proportion of health deficits an individual has accumulated, from a selection… 
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References

SHOWING 1-10 OF 155 REFERENCES
Dynamical network model for age-related health deficits and mortality.
TLDR
A dynamical network model of deficits is used to explore the effects of interactions between deficits, deficit damage and repair processes, and the connection between the F and mortality, and qualitatively reproduce Gompertz's law of increasing human mortality with age.
Network model of human aging: Frailty limits and information measures.
TLDR
Mutual information I is used to provide a nonparametric measure of the predictive value of the FI with respect to individual mortality and it is found that I is only modestly degraded by q<1, and this degradation is mitigated when increasing number of deficits are included in the FI.
Assessing biological aging: the origin of deficit accumulation
TLDR
A stochastic dynamics framework is applied to illustrate that the average number of deficits present in an individual is the product of the average intensity of the environmental stresses and the average recovery time, and suggests that targeting the recovery rate will decrease the number of deficit that individuals accumulate and thereby benefit life expectancy.
Accumulation of Deficits as a Proxy Measure of Aging
TLDR
The formula for estimating an individual's life span given the frailty index value is presented and it is proposed that it may be used as a proxy measure of aging.
Evolution of networks
TLDR
The recent rapid progress in the statistical physics of evolving networks is reviewed, and how growing networks self-organize into scale-free structures is discussed, and the role of the mechanism of preferential linking is investigated.
Heterogeneity of Human Aging and Its Assessment
TLDR
The performance of five measures of health heterogeneity are analyzed, judging them by their ability to predict mortality, and it is found that the FI-combined showed the best mortality prediction in an age-adjusted model.
A Frailty Index Based On Deficit Accumulation Quantifies Mortality Risk in Humans and in Mice
TLDR
Quantifying deficit accumulation in individual mice provides a powerful new tool that can facilitate translation of research on ageing, including in relation to disease.
The architecture of complex weighted networks.
TLDR
This work studies the scientific collaboration network and the world-wide air-transportation network, which are representative examples of social and large infrastructure systems, respectively, and defines appropriate metrics combining weighted and topological observables that enable it to characterize the complex statistical properties and heterogeneity of the actual strength of edges and vertices.
The application of information theory for the research of aging and aging-related diseases
...
...