ArticleBiogerontology2021
Evidence from two cohorts for the frailty syndrome as an emergent state of parallel dysregulation in multiple physiological systems.
Article in Biogerontology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 55 citations in OpenAlex.
- Frailty and outcomes in older adults hospitalized for epilepsy: a nationwide inpatient sample study.BMC geriatrics · 2026Article
- Association between frailty and MACE and all-cause mortality in Chinese maintenance haemodialysis patients: a retrospective cohort study.BMC nephrology · 2026Article
- Characterization of Dynamic Adaptation to Stressors Using Multisystem Stimulus-Response Data: The Study of Physical Resilience in Aging Pilot.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Frailty and comorbidities among young adult cancer survivors enrolled in an mHealth physical activity intervention trial.Journal of cancer survivorship : research and practice · 2025Article
- Associating frailty and dynamic dysregulation between motor and cardiac autonomic systems.Frontiers in aging · 2024Article
- Physiological Dysregulation Proceeds and Predicts Health Outcomes Similarly in Chinese and Western Populations.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
- Frailty detection in older adults via fractal analysis of acceleration signals from wrist-worn sensors.Health information science and systems · 2023Article
- [Frailty phenotype and risk factor for disturbed sleep].Zeitschrift fur Gerontologie und Geriatrie · 2023Review
- Aging-Related Multisystem Dysregulation Over the Adult Life Span and Physical Function in Later Life: The Atherosclerosis Risk in Communities (ARIC) Study.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- Frailty and Comorbidities Among Young Adult Cancer Survivors Enrolled in an mHealth Physical Activity Intervention Trial.Research square · 2023Article
- Multisystem physiological perspective of human frailty and its modulation by physical activity.Physiological reviews · 2023Review
- Intercorrelated variability in blood and hemodynamic biomarkers reveals physiological network in hemodialysis patients.Scientific reports · 2023Article
- Assessment of Physical Resilience Using Residual Methods and Its Association With Adverse Outcomes in Older Adults.Innovation in aging · 2023Article
- Multidimensional associations between nutrient intake and healthy ageing in humans.BMC biology · 2022Article
- Chronotropic Response and Heart Rate Variability before and after a 160 m Walking Test in Young, Middle-Aged, Frail, and Non-Frail Older Adults.International journal of environmental research and public health · 2022Article
- Synchrony of biomarker variability indicates a critical transition: Application to mortality prediction in hemodialysis.iScience · 2022Article
- Frailty Risks of Prescription Analgesics and Sedatives across Frailty Models: the Health and Retirement Study.Drugs & aging · 2022Article
- An objective metric of individual health and aging for population surveys.Population health metrics · 2022Article
- Frailty assessment using a novel approach based on combined motor and cardiac functions: a pilot study.BMC geriatrics · 2022Article
- Immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in older residents of a long-term care facility: relation with age, frailty and prior infection status.Biogerontology · 2022Observational
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Frailty is a clinical syndrome often present in older adults and characterized by a heightened vulnerability to stressors. The biological antecedents and etiology of frailty are unclear despite decades of research: frailty is associated with dysregulation in a wide range of physiological systems, but no specific cause has been identified. Here, we test predictions stemming from the hypothesis that there is no specific cause: that frailty is an emergent property arising from the complex systems dynamics of the broad loss of organismal homeostasis. Specifically, we use dysregulation of six physiological systems using the Mahalanobis distance approach in two cohorts of older adults to test the breadth, diffuseness, and nonlinearity of associations between frailty and system-specific dysregulation. We find clear support for the breadth of associations between frailty and physiological dysregulation: positive associations of all systems with frailty in at least some analyses. We find partial support for diffuseness: the number of systems or total amount of dysregulation is more important than the identity of the systems dysregulated, but results only partially replicate across cohorts. We find partial support for nonlinearity: trends are exponential but not always significantly so, and power is limited for groups with very high levels of dysregulation. Overall, results are consistent with-but not definitive proof of-frailty as an emergent property of complex systems dynamics. Substantial work remains to understand how frailty relates to underlying physiological dynamics across systems.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.