Homeostatic dysregulation proceeds in parallel in multiple physiological systems

Qing Li, Shengrui Wang, Emmanuel Milot, Patrick Bergeron, Luigi Ferrucci, Linda P Fried, Alan A. Cohen

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1103-1112
Number of pages10
JournalAging Cell
Volume14
Issue number6
DOIs
StatePublished - Dec 1 2015

Fingerprint

Biomarkers
Health
Vitamins
Electrolytes
Immune System
Heart Diseases
Chronic Disease
Research Personnel
Oxygen
Lipids
Mortality
Liver
Datasets

Keywords

  • Aging
  • Biomarker
  • Homeostasis
  • Multi-system dysregulation
  • Physiology
  • Statistical distance

ASJC Scopus subject areas

  • Cell Biology
  • Aging

Cite this

Li, Q., Wang, S., Milot, E., Bergeron, P., Ferrucci, L., Fried, L. P., & Cohen, A. A. (2015). Homeostatic dysregulation proceeds in parallel in multiple physiological systems. Aging Cell, 14(6), 1103-1112. https://doi.org/10.1111/acel.12402

Homeostatic dysregulation proceeds in parallel in multiple physiological systems. / Li, Qing; Wang, Shengrui; Milot, Emmanuel; Bergeron, Patrick; Ferrucci, Luigi; Fried, Linda P; Cohen, Alan A.

In: Aging Cell, Vol. 14, No. 6, 01.12.2015, p. 1103-1112.

Research output: Contribution to journalArticle

Li, Q, Wang, S, Milot, E, Bergeron, P, Ferrucci, L, Fried, LP & Cohen, AA 2015, 'Homeostatic dysregulation proceeds in parallel in multiple physiological systems', Aging Cell, vol. 14, no. 6, pp. 1103-1112. https://doi.org/10.1111/acel.12402
Li, Qing ; Wang, Shengrui ; Milot, Emmanuel ; Bergeron, Patrick ; Ferrucci, Luigi ; Fried, Linda P ; Cohen, Alan A. / Homeostatic dysregulation proceeds in parallel in multiple physiological systems. In: Aging Cell. 2015 ; Vol. 14, No. 6. pp. 1103-1112.
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