Mechanisms of ageing and developmentAug 23, 2026

Body’s balance problems and internal clocks from a distance-based view

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 24, 2026

Abstract

Aging may involve a departure from physiological balance, which could be assessed through homeostatic dysregulation and supervised aging measures.

Homeostatic dysregulation summarizes deviations from a defined reference distribution related to aging.
Supervised aging measures are model outputs designed to predict various outcomes, including age and health status.
The correlation between homeostatic dysregulation and supervised aging measures is often modest.
Joint assessment of these measures may be useful for specific risk stratification and monitoring.
Prospective validation and calibration are necessary to confirm the additional value of these measures over chronological age.

Simplified

Aging can be viewed as a progressive departure from physiological homeostasis accompanied by increasing morbidity and mortality risk. This perspective motivates two complementary but non-equivalent approaches. The first is homeostatic dysregulation (HD), which summarizes multivariate deviation from a prespecified reference distribution. The second comprises supervised aging measures, which are target-dependent model outputs trained to predict outcomes such as chronological age, mortality, morbidity, functional status, or pace of aging. Their outputs are often only modestly correlated and do not represent the same latent biological age or a geometric distance. We propose that their joint value should be tested for outcome-specific risk stratification, longitudinal monitoring, and gerotherapeutic trials. Such applications require prospective validation, calibration, and evidence that each measure adds information beyond chronological age and established clinical predictors.

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Body’s balance problems and internal clocks from a distance-based view

Abstract

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