ArticleAging cell2015
Homeostatic dysregulation proceeds in parallel in multiple physiological systems.
Article in Aging cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed.
- Validation of a Deficit-Accumulation Frailty Index in the ASPirin in Reducing Events in the Elderly Study and Its Predictive Capacity for Disability-Free Survival.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Trial
- Effect of Diet, Exercise, or Both on Biological Age and Healthy Aging in Older Adults with Obesity: Secondary Analysis of a Randomized Controlled Trial.The journal of nutrition, health & aging · 2022Trial
- Trial
- Change in the Rate of Biological Aging in Response to Caloric Restriction: CALERIE Biobank Analysis.The journals of gerontology. Series A, Biological sciences and medical sciences · 2017Trial
- Physiological Age and Homeostatic Dysregulation Following Child Maltreatment in Youth.Molecular psychiatry · 2026Article
- A lipidomic based metabolic age score for monitoring the effects of lifestyle and diet on metabolic disease risk.Research square · 2026Article
- Biological age acceleration and extrahepatic multimorbidity in U.S. adults with metabolic dysfunction-associated steatotic liver disease: a national cross-sectional study.Clinical and experimental hepatology · 2026Article
- Mitochondria-targeted delivery strategies for age-related diseases.International journal of pharmaceutics: X · 2026Review
- Association between essential trace elements, dietary patterns, and biological aging.European journal of nutrition · 2026Article
- System-level clustering of testosterone-related biomarkers identifies high-risk aging profiles linked to inflammation and renal function.Communications medicine · 2026Article
- Entropy of Muscle Fiber Histology Predicts Mobility in Older Adults: The Study of Muscle, Mobility, and Aging.Aging cell · 2026Article
- Exploring frailty in the context of HIV and aging in Kazakhstan: findings from a pilot cross-sectional study.BMC public health · 2026Article
- Joint Association of Diet Index for Gut Microbiota and MVPA With Central Obesity: The Mediating Role of Biological Age.Food science & nutrition · 2026Article
- Association between dietary patterns and biological aging among Chinese middle-aged and older adults: evidence from a cross-sectional study.Frontiers in nutrition · 2026Article
- Associations of physical activity domains and delayed biological aging: assessing heterogeneity and interaction of effects.Biology of sport · 2026Article
- Frailty Meets Cardio-oncology: A New Frontier in Personalised Cancer Care.European cardiology · 2026Review
- Predictors of postoperative complications in elderly patients undergoing pulmonary lobectomy: a retrospective cohort study.Frontiers in medicine · 2026Article
- Aging as Entropy: A Quantifiable Framework.Endocrinology and metabolism (Seoul, Korea) · 2025Article
- Entropy, Assessed by Homeostatic Dysregulation on Electrocardiograms Predicts Fracture and Mortality.Aging cell · 2025Article
- Entropy and Human Aging.Aging cell · 2025Article
43 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
An increasing number of aging researchers believes that multi-system physiological dysregulation may be a key biological mechanism of aging, but evidence of this has been sparse. Here, we used biomarker data on nearly 33, 000 individuals from four large datasets to test for the presence of multi-system dysregulation. We grouped 37 biomarkers into six a priori groupings representing physiological systems (lipids, immune, oxygen transport, liver function, vitamins, and electrolytes), then calculated dysregulation scores for each system in each individual using statistical distance. Correlations among dysregulation levels across systems were generally weak but significant. Comparison of these results to dysregulation in arbitrary 'systems' generated by random grouping of biomarkers showed that a priori knowledge effectively distinguished the true systems in which dysregulation proceeds most independently. In other words, correlations among dysregulation levels were higher using arbitrary systems, indicating that only a priori systems identified distinct dysregulation processes. Additionally, dysregulation of most systems increased with age and significantly predicted multiple health outcomes including mortality, frailty, diabetes, heart disease, and number of chronic diseases. The six systems differed in how well their dysregulation scores predicted health outcomes and age. These findings present the first unequivocal demonstration of integrated multi-system physiological dysregulation during aging, demonstrating that physiological dysregulation proceeds neither as a single global process nor as a completely independent process in different systems, but rather as a set of system-specific processes likely linked through weak feedback effects. These processes--probably many more than the six measured here--are implicated in aging.
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