Plasma metabolomic markers underlying skeletal muscle mitochondrial function relationships with cognition and motor function.

Autor:	Tian Q; Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA., Greig EE; Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA., Walker KA; Laboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Baltimore, MD 21224, USA., Fishbein KW; Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD 21224, USA., Spencer RG; Laboratory of Clinical Investigation, National Institute on Aging, NIH, Baltimore, MD 21224, USA., Resnick SM; Laboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Baltimore, MD 21224, USA., Ferrucci L; Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Jazyk:	angličtina
Zdroj:	Age and ageing [Age Ageing] 2024 Apr 01; Vol. 53 (4).
DOI:	10.1093/ageing/afae079
Abstrakt:	Background: Lower skeletal muscle mitochondrial function is associated with future cognitive impairment and mobility decline, but the biological underpinnings for these associations are unclear. We examined metabolomic markers underlying skeletal muscle mitochondrial function, cognition and motor function. Methods: We analysed data from 560 participants from the Baltimore Longitudinal Study of Aging (mean age: 68.4 years, 56% women, 28% Black) who had data on skeletal muscle oxidative capacity (post-exercise recovery rate of phosphocreatine, kPCr) via 31P magnetic resonance spectroscopy and targeted plasma metabolomics using LASSO model. We then examined which kPCr-related markers were also associated with cognition and motor function in a larger sample (n = 918, mean age: 69.4, 55% women, 27% Black). Results: The LASSO model revealed 24 metabolites significantly predicting kPCr, with the top 5 being asymmetric dimethylarginine, lactic acid, lysophosphatidylcholine a C18:1, indoleacetic acid and triacylglyceride (17:1_34:3), also significant in multivariable linear regression. The kPCr metabolite score was associated with cognitive or motor function, with 2.5-minute usual gait speed showing the strongest association (r = 0.182). Five lipids (lysophosphatidylcholine a C18:1, phosphatidylcholine ae C42:3, cholesteryl ester 18:1, sphingomyelin C26:0, octadecenoic acid) and 2 amino acids (leucine, cystine) were associated with both cognitive and motor function measures. Conclusion: Our findings add evidence to the hypothesis that mitochondrial function is implicated in the pathogenesis of cognitive and physical decline with aging and suggest that targeting specific metabolites may prevent cognitive and mobility decline through their effects on mitochondria. Future omics studies are warranted to confirm these findings and explore mechanisms underlying mitochondrial dysfunction in aging phenotypes. (Published by Oxford University Press on behalf of the British Geriatrics Society 2024.)
Databáze:	MEDLINE
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