Data from multi-national aging cohorts show dysregulated metabolic pathways in people with physio-cognitive decline
Abstract Background 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 poo...
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Nature Portfolio
2025-08-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-01073-5 |
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| author | Yi-Long Huang Wei-Ju Chang Chao-Hsiung Lin Shu Zhang Yukiko Nishita Rei Otsuka Wei-Ju Lee Chih-Kuang Liang Ming-Yueh Chou Li-Ning Peng Hidenori Arai Luigi Ferrucci Liang-Kung Chen |
| author_facet | Yi-Long Huang Wei-Ju Chang Chao-Hsiung Lin Shu Zhang Yukiko Nishita Rei Otsuka Wei-Ju Lee Chih-Kuang Liang Ming-Yueh Chou Li-Ning Peng Hidenori Arai Luigi Ferrucci Liang-Kung Chen |
| author_sort | Yi-Long Huang |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| format | Article |
| id | doaj-art-d1793bd753bc404e96df0e4804815fd6 |
| institution | DOAJ |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-d1793bd753bc404e96df0e4804815fd62025-08-20T03:06:04ZengNature PortfolioCommunications Medicine2730-664X2025-08-01511910.1038/s43856-025-01073-5Data from multi-national aging cohorts show dysregulated metabolic pathways in people with physio-cognitive declineYi-Long Huang0Wei-Ju Chang1Chao-Hsiung Lin2Shu Zhang3Yukiko Nishita4Rei Otsuka5Wei-Ju Lee6Chih-Kuang Liang7Ming-Yueh Chou8Li-Ning Peng9Hidenori Arai10Luigi Ferrucci11Liang-Kung Chen12Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung UniversityCenter for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung UniversityCenter for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung UniversityDepartment of Epidemiology of Aging, National Center for Geriatrics and GerontologyDepartment of Epidemiology of Aging, National Center for Geriatrics and GerontologyDepartment of Epidemiology of Aging, National Center for Geriatrics and GerontologyDepartment of Family Medicine, Taipei Veterans General Hospital Yuanshan BranchCenter for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung UniversityCenter for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung UniversityCenter for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung UniversityNational Center for Geriatrics and GerontologyLongitudinal Studies Section, National Institute on AgingCenter for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung UniversityAbstract Background 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. Methods 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. Results 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. Conclusions 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.https://doi.org/10.1038/s43856-025-01073-5 |
| spellingShingle | Yi-Long Huang Wei-Ju Chang Chao-Hsiung Lin Shu Zhang Yukiko Nishita Rei Otsuka Wei-Ju Lee Chih-Kuang Liang Ming-Yueh Chou Li-Ning Peng Hidenori Arai Luigi Ferrucci Liang-Kung Chen Data from multi-national aging cohorts show dysregulated metabolic pathways in people with physio-cognitive decline Communications Medicine |
| title | Data from multi-national aging cohorts show dysregulated metabolic pathways in people with physio-cognitive decline |
| title_full | Data from multi-national aging cohorts show dysregulated metabolic pathways in people with physio-cognitive decline |
| title_fullStr | Data from multi-national aging cohorts show dysregulated metabolic pathways in people with physio-cognitive decline |
| title_full_unstemmed | Data from multi-national aging cohorts show dysregulated metabolic pathways in people with physio-cognitive decline |
| title_short | Data from multi-national aging cohorts show dysregulated metabolic pathways in people with physio-cognitive decline |
| title_sort | data from multi national aging cohorts show dysregulated metabolic pathways in people with physio cognitive decline |
| url | https://doi.org/10.1038/s43856-025-01073-5 |
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