Measuring Aging’s Biological Disorganization

A New Metric Quantifies Systemic Disorganization as We Age

A preprint posted to medRxiv introduces a new method to measure the progressive loss of biological order during aging. An international team of researchers led by Menglan Hao and Xiaoqian Wang has developed a computational tool, called Distance of Covariance (DISCO), to calculate “entropy” across the body’s organ systems. The study analyzed data from over 500,000 individuals across five large cohorts, including the UK Biobank and the US National Health and Nutrition Examination Survey.

DISCO Predicts Mortality and Frailty by Measuring Systemic Noise

The researchers validated DISCO across four types of biological data: standard clinical blood biomarkers, blood proteomics, metabolomics, and gut microbiome profiles. In each case, DISCO scores increased with age. Critically, these scores were not just a correlate of time. In the UK Biobank, a high DISCO score calculated from 19 routine blood tests was a stronger predictor of all-cause mortality over a 14-year period than established metrics of biological dysregulation like the “homeostatic dysregulation” index.

DISCO performed comparably to the best epigenetic clocks, such as GrimAge, in mortality prediction. It also strongly correlated with and predicted the onset of frailty. The tool was effective across diverse populations, showing consistent results in British, American, and Chinese cohorts.

Entropy Spreads Freely Across Organ Systems

A central finding came from applying DISCO to organ-specific proteins. The team created entropy scores for 11 major organ systems, including the brain, heart, kidney, and liver, based on protein levels in blood plasma. The analysis revealed that entropy is not confined. Instead, it shows high interconnectivity across all organ networks.

“We observed little to no specificity of a given organ predicting its own diseases and mortality,” the authors note. High entropy in the liver system, for example, was as predictive of future heart disease as it was of liver disease. This suggests that while clinical disease manifests in a specific organ, the underlying state of disorganization is a whole-body phenomenon.

Network analysis identified which organ systems were most central to this web of dysfunction. The brain emerged as a critical hub. For nearly every cause of mortality analyzed—from cardiovascular disease to cancer—a high brain entropy score was among the top predictors. This indicates that the brain’s systemic connectedness may make its functional integrity especially important for overall organismal aging.

Implications for Measuring and Understanding Aging

The study proposes that successful aging is less about the state of individual parts and more about the quality of communication and coordination between them. The DISCO metric frames aging as a rise in systemic entropy, where the complex, ordered relationships between biological components break down into noise.

This has practical implications. A blood test measuring a panel of organ-specific proteins could one day provide a personalized map of systemic entropy, highlighting which interconnected networks are most disrupted. Therapeutically, the findings argue against approaches that target single organs in isolation. Instead, they support interventions aimed at improving system-wide coordination and resilience, such as exercise or therapies that enhance metabolic or vascular health.

The work is currently a preprint and has not undergone peer review. A key limitation is its observational nature; it identifies associations but cannot prove causality. The biological mechanisms by which entropy spreads between organs remain to be determined. Furthermore, while DISCO is a powerful statistical tool, its clinical utility requires prospective validation in independent populations.

“Our findings challenge current notions of independent organ-specific aging signatures,” the authors conclude. Health during aging, they argue, requires integrated homeostatic coordination across the entire organism.

Source:
Human aging reflects increases in entropy across organ networks (medRxiv preprint, 2026-04-26)