1. The mediating role of kynurenine pathway metabolites on the relationship between inflammation and muscle mass in oldest-old men.
- Author
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Hetherington-Rauth, Megan, Johnson, Eileen, Migliavacca, Eugenia, Langsetmo, Lisa, Hepple, Russell T, Ryan, Terence E, Ferrucci, Luigi, Breuillé, Denis, Corthesy, John, Lane, Nancy E, Feige, Jérôme N, Napoli, Nicola, Tramontana, Flavia, Orwoll, Eric S, and Cawthon, Peggy M
- Subjects
C-reactive protein ,D3-creatine ,biomarkers ,sarcopenia ,Clinical Sciences ,Gerontology ,Biomedical and clinical sciences ,Health sciences - Abstract
Tryptophan (TRP) metabolites along the kynurenine (KYN) pathway (KP) have been found to influence muscle. Pro-inflammatory cytokines are known to stimulate the degradation of TRP down the KP. Given that both inflammation and KP metabolites have been connected with loss of muscle, we assessed the potential mediating role of KP metabolites on inflammation and muscle mass in older men. 505 men (85.0±4.2yrs) from the Osteoporotic Fractures in Men cohort study with measured D3-creatine dilution (D3Cr) muscle mass, KP metabolites, and inflammation markers (C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP) and a subsample (n=305) with interleukin (IL-6, IL-1β, IL-17A) and tumor necrosis factor-α (TNF-α)) were included in the analysis. KP metabolites and inflammatory markers were measured using liquid chromatography-tandem mass spectrometry and immunoassays, respectively. 23-92% of the inverse relationship between inflammatory markers and D3Cr muscle mass was mediated by KP metabolites (indirect effect p0.05). KP metabolites, particularly higher ratios of KYN/TRP, 3-HK/XA, 3-HK/3-HAA, QA/3-HAA and a lower ratio of NAM/QA, mediated the relationship between inflammation and low muscle mass. Our preliminary cross-sectional data suggest that interventions to alter D3Cr muscle mass may focus on KP metabolites rather than inflammation per se.
- Published
- 2024