Using Physiological System Networks to Elaborate Resilience Across Frailty States

Author:

Hao Meng12,Zhang Hui13ORCID,Li Yi14ORCID,Hu Xiaoxi15,Hu Zixin15,Jiang Xiaoyan36,Wang Jiucun15,Sun Xuehui13,Liu Zuyun7ORCID,Davis Daniel8ORCID,Jin Li15,Wang Xiaofeng19

Affiliation:

1. State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University , Shanghai , China

2. Fudan Zhangjiang Institute , Shanghai , China

3. Fudan University People’s Hospital of Rugao Joint Research Institute of Longevity and Aging , Rugao, Jiangsu Province , China

4. International Human Phenome Institutes , Shanghai , China

5. Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University , Shanghai , China

6. Key Laboratory of Arrhythmias, Ministry of Education, Department of Pathology and Pathophysiology, School of Medicine, Tongji University , Shanghai , China

7. School of Public Health, Zhejiang University School of Medicine , Hangzhou, Zhejiang , China

8. MRC Unit for Lifelong Health and Ageing at UCL , London , UK

9. National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University , Shanghai , China

Abstract

Abstract Background Aging is characterized by loss of resilience, the ability to resist or recover from stressors. Network analysis has shown promise in investigating dynamic relationships underlying resilience. We aimed to use network analysis to measure resilience in a longitudinal cohort of older adults and quantify whole-system vulnerabilities associated with frailty. Methods We used data from the Rugao Longitudinal Ageing Study, including 71 biomarkers from participants classified as robust, prefrail, or frail. We quantified biomarker correlations and topological parameters. Additionally, we proposed propagation models to simulate damage and recovery dynamics, investigating network resilience under various conditions. Results We classified 1 754 individuals into robust (n = 369), prefrail (n = 1 103), and frail (n = 282) groups with 71 biomarkers. Several biomarkers were linked to frailty, including those related to blood pressure, electrocardiogram (ECG), kidney function, platelets, and white blood cells. Each frailty stage was associated with increased network correlations. The frail network showed increased average degree and connectance, decreased average path length and diameter, and reduced modularity compared to robust and prefrail networks. Hub biomarkers, particularly β2-microglobulin and platelet count, played a significant role, potentially propagating dysfunction across physiological systems. Simulations revealed that damage to critical hubs led to longer recovery times in the frail network than robust and prefrail networks. Conclusions Network analysis could serve as a valuable tool for quantifying resilience and identifying vulnerabilities in older adults with frailty. Our findings contribute to understanding frailty-related physiological disturbances and offer potential for personalized healthcare interventions targeting resilience in older populations.

Funder

National Natural Science Foundation of China

Shanghai Sailing Program

Shanghai Municipal Science and Technology Major Project

Medical Research Council

Publisher

Oxford University Press (OUP)

Subject

Geriatrics and Gerontology,Aging

Reference40 articles.

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