Physiological Dysregulation Proceeds and Predicts Health Outcomes Similarly in Chinese and Western Populations

J Gerontol A Biol Sci Med Sci. 2024 Jan 1;79(1):glad146. doi: 10.1093/gerona/glad146.


Background: A decade ago, we proposed an index of physiological dysregulation based on Mahalanobis distance (DM) that measures how far from the norm an individual biomarker profile is. While extensive validation has been performed, focus was mostly on Western populations with little comparison to developing countries, particularly at a physiological system level. The degree to which the approach would work in other sociocultural contexts and the similarity of dysregulation signatures across diverse populations are still open questions.

Methods: Using 2 data sets from China and 3 from Western countries (United States, United Kingdom, and Italy), we calculated DM globally and per physiological system. We assessed pairwise correlations among systems, difference with age, prediction of mortality and age-related diseases, and sensitivity to interchanging data sets with one another as the reference in DM calculation.

Results: Overall, results were comparable across all data sets. Different physiological systems showed distinct dysregulation processes. Association with age was moderate and often nonlinear, similarly for all populations. Mahalanobis distance predicted most health outcomes, although differently by physiological system. Using a Chinese population as the reference when calculating DM for Western populations, or vice versa, led to similar associations with health outcomes, with a few exceptions.

Conclusions: While small differences were noticeable, they did not systematically emerge between Chinese and Western populations, but rather diffusively across all data sets. These findings suggest that DM presents similar properties, notwithstanding sociocultural backgrounds, and that it is equally effective in capturing the loss of homeostasis that occurs during aging in diverse industrial human populations.

Keywords: Aging; Homeostatic dysregulation; Mahalanobis distance; Mortality; Physiological systems.

MeSH terms

  • Aging* / physiology
  • Biomarkers
  • China
  • Homeostasis
  • Humans
  • Outcome Assessment, Health Care*
  • United States


  • Biomarkers