Proteo-metabolomic insights for early dual physical and cognitive impairments: A search for biomarkers of healthy aging based on muscle-brain crosstalk.

Yi-Long Huang, Wei-Ju Chang, Chen-Hua Huang, Chao-Hsiung Lin, Li-Ning Peng, Chih-Ping Chung, Liang-Kung Chen, Wei-Ju Lee

Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan. · pubmed

Paper

Abstract

We employed an untargeted proteo-metabolomic approach to profile circulating biomarkers in plasma samples from the I-Lan Longitudinal Aging Study, aiming to identify biomarkers and pathways associated with physio-cognitive decline syndrome (PCDS). In 115 propensity score-matched PCDS case-control pairs, pathway analyses implicated dysregulation of fatty acid metabolism and inflammation in PCDS pathogenesis. Sex-specific associations were observed, with disruptions in central carbon metabolism (elevated PKM, MDH1, and GAPDH; decreased MINPP1) and tyrosine metabolism (decreased MIF, DBH; increased thyroxine) characterizing in men. In contrast, perturbations in glutathione and phenylalanine metabolism, including increased ANPEP, GSTP1, and decreased pyroglutamic acid, were identified in women. Results suggest that dysregulated energy and redox homeostasis likely contribute to PCDS development. Notably, ANPEP, PKM, and MIF emerged as potential biomarkers, elucidating the muscle-brain crosstalk framework. Our findings provide insights into potential molecular mechanisms underlying PCDS and the muscle-brain crosstalk, marking progress toward elucidating biomarkers in the journey of healthy aging.

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Research summary

The paper investigates biomarkers associated with physio-cognitive decline syndrome (PCDS) and explores the underlying molecular mechanisms, which are relevant to understanding aging processes. However, while it provides insights into potential biomarkers and metabolic pathways, the findings appear to be more focused on symptomatology rather than addressing the root causes of aging or lifespan extension. Thus, while it contributes solid research to the field, its overall impact is limited.

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