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Data from multi-national aging cohorts show dysregulated metabolic pathways in people with physio-cognitive decline

Year: 2025

Type: article

Abstract: Physio-cognitive decline (PCD) represents a dual impairment of mobility and cognitive function in aging populations, significantly increasing risks of disability, dementia, and mortality. Despite its clinical importance, the underlying biological mechanisms driving PCD remain poorly understood. This study aimed to identify metabolomic biomarkers and pathways associated with PCD to elucidate potential mechanistic insights. We conducted a comparative metabolomic analysis using serum samples from aging cohorts in Taiwan and Japan. A total of 197 pairs of participants were selected, comparing individuals in the top quintile (robust) versus bottom quintile (PCD) for both mobility and cognitive performance. Untargeted metabolomic profiling was performed to identify differential metabolites and dysregulated pathways. Here, we show significant alterations in 606 differential metabolites and 17 metabolic pathways in PCD individuals compared to robust controls. Key dysregulated pathways include glutathione metabolism, tryptophan metabolism, urea cycle/amino group metabolism, and bile acid biosynthesis. Eleven metabolites are confirmed as potential biomarkers, including creatinine, pyroglutamic acid, melatonin, 3-hydroxykynurenine, 5-hydroxytryptophan, taurodeoxycholic acid, glycocholic acid and 7α-hydroxycholesterol. This study defines the comprehensive metabolomic signature of PCD, revealing disrupted metabolic pathways and identifying promising biomarker candidates for early detection and monitoring of physio-cognitive decline in aging populations. With advancing age, some individuals experience a concurrent decline in physical mobility and cognitive function, a status termed physio-cognitive decline (PCD), which increases the risk of severe health issues. This study aimed to investigate the underlying biological causes of this status by identifying specific markers in the bloodstream. We analyzed blood samples from older adults in Taiwan and Japan, comparing individuals with PCD to their robustly healthy counterparts. We found differences in eleven key components in the blood for which the biological function is well understood. These findings provide insight into the biological disruptions during PCD and may support the future development of a blood test for earlier identification of at-risk individuals. Huang et al. investigate serum metabolomic profiles from aging cohorts in Taiwan and Japan to identify biomarkers of physio-cognitive decline syndrome. They report significant alterations in glutathione, tryptophan, and bile acid pathways, with metabolites including creatinine and 3-hydroxykynurenine as potential indicators.

Source: Communications Medicine

DOI: 10.1038/s43856-025-01073-5