Trial reportMechanisms of ageing and development
Trajectories of physiological dysregulation predicts mortality and health outcomes in a consistent manner across three populations.
Trial report in Mechanisms of ageing and development. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 75 citations in OpenAlex.
- Association between essential trace elements, dietary patterns, and biological aging.European journal of nutrition · 2026Article
- Encouraging a move toward precision geromedicine.Geromedicine · 2026Article
- No winners or losers: clinical chemistry-based biological aging metrics perform similarly across cohorts and health outcomes.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Measuring the Interrelationships Between Cognitive Performance, Race/Ethnicity, Discrimination, Health Behaviors, and Physiological Dysregulation: A Path Analysis of the Multi-Ethnic Study of Atherosclerosis.Journal of aging and health · 2025Article
- Pilot application of an inflammation and physiological dysregulation index based on noninvasive salivary biomarkers.BMC research notes · 2025Article
- Physiological phenotypes have optimal values relevant to healthy aging: sweet spots deduced from the Canadian Longitudinal Study on Aging.GeroScience · 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
- Age-related physiological dysregulation progresses slowly in semi-free-ranging chimpanzees.Evolution, medicine, and public health · 2024Article
- Associating frailty and dynamic dysregulation between motor and cardiac autonomic systems.Frontiers in aging · 2024Article
- Application of early warning signs to physiological contexts: a comparison of multivariate indices in patients on long-term hemodialysis.Frontiers in network physiology · 2024Article
- 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
- Multidimensional associations between nutrient intake and healthy ageing in humans.BMC biology · 2022Article
- Synchrony of biomarker variability indicates a critical transition: Application to mortality prediction in hemodialysis.iScience · 2022Article
- An objective metric of individual health and aging for population surveys.Population health metrics · 2022Article
- A holistic approach to predicting diabetes risk via biomarkers.EBioMedicine · 2021Article
- Development and Validation of 2 Composite Aging Measures Using Routine Clinical Biomarkers in the Chinese Population: Analyses From 2 Prospective Cohort Studies.The journals of gerontology. Series A, Biological sciences and medical sciences · 2021Article
- Evidence from two cohorts for the frailty syndrome as an emergent state of parallel dysregulation in multiple physiological systems.Biogerontology · 2021Article
- Physiological Dysregulation, Frailty, and Impacts on Adverse Health and Functional Outcomes.Frontiers in medicine · 2021Article
- Prediction of Mortality in Hemodialysis Patients Using Moving Multivariate Distance.Frontiers in physiology · 2021Article
- Insights from evolutionarily relevant models for human ageing.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Mechanistic and evolutionary perspectives both agree that aging involves multiple integrated biochemical networks in the organism. In particular, the homeostatic physiological dysregulation (PD) hypothesis contends that aging is caused by the progressive breakdown of key regulatory processes. However, nothing is yet known about the specifics of how PD changes with age and affects health. Using a recently validated measure of PD involving the calculation of a multivariate distance (DM) from biomarker data, we show that PD trajectories predict mortality, frailty, and chronic diseases (cancer, cardiovascular diseases, and diabetes). Specifically, relative risks of outcomes associated with individual slopes in (i.e. rate of) dysregulation range 1.20-1.40 per unit slope. We confirm the results by replicating the analysis using two suites of biomarkers selected with markedly different criteria and, for mortality, in three longitudinal cohort-based studies. Overall, the consistence of effect sizes (direction and magnitude) across data sets, biomarker suites and outcomes suggests that the positive relationship between DM and health outcomes is a general phenomenon found across human populations. Therefore, the study of dysregulation trajectories should allow important insights into aging physiology and provide clinically meaningful predictors of outcomes.
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