Marron Megan M, Harris Tamara B, Boudreau Robert M, Clish Clary B, Moore Steven C, Murphy Rachel A, Murthy Venkatesh L, Sanders Jason L, Shah Ravi V, Tseng George C, Wendell Stacy G, Zmuda Joseph M, Newman Anne B
Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, MD 20814, USA.
Metabolites. 2019 Apr 30;9(5):83. doi: 10.3390/metabo9050083.
Black versus white older Americans are more likely to experience frailty, a condition associated with adverse health outcomes. To reduce racial disparities in health, a complete understanding of the pathophysiology of frailty is needed. Metabolomics may further our understanding by characterizing differences in the body during a vigorous versus frail state. We sought to identify metabolites and biological pathways associated with vigor to frailty among 287 black men ages 70-81 from the Health, Aging, and Body Composition study. Using liquid chromatography-mass spectrometry, 350 metabolites were measured in overnight-fasting plasma. The Scale of Aging Vigor in Epidemiology (SAVE) measured vigor to frailty based on weight change, strength, energy, gait speed, and physical activity. Thirty-seven metabolites correlated with SAVE scores ( < 0.05), while adjusting for age and site. Fourteen metabolites remained significant after multiple comparisons adjustment (false discovery rate < 0.30). Lower values of tryptophan, methionine, tyrosine, asparagine, C14:0 sphingomyelin, and 1-methylnicotinamide, and higher values of glucoronate, N-carbamoyl-beta-alanine, isocitrate, creatinine, C4-OH carnitine, cystathionine, hydroxyphenylacetate, and putrescine were associated with frailer SAVE scores. Pathway analyses identified nitrogen metabolism, aminoacyl-tRNA biosynthesis, and the citric acid cycle. Future studies need to confirm these SAVE-associated metabolites and pathways that may indicate novel mechanisms involved in the frailty syndrome.
美国老年黑人比老年白人更容易出现身体虚弱的情况，而身体虚弱与不良健康后果相关。为了减少健康方面的种族差异，需要全面了解身体虚弱的病理生理学。代谢组学可以通过描述身体在活力状态与虚弱状态下的差异，进一步增进我们的理解。我们试图在“健康、衰老和身体成分”研究中，从287名年龄在70至81岁的黑人男性中，找出与从活力到虚弱相关的代谢物和生物途径。使用液相色谱-质谱联用技术，对空腹过夜血浆中的350种代谢物进行了测量。流行病学衰老活力量表（SAVE）基于体重变化、力量、能量、步速和身体活动来衡量从活力到虚弱的程度。在调整年龄和研究地点后，有37种代谢物与SAVE评分相关（P<0.05）。经过多重比较调整（错误发现率<0.30）后，14种代谢物仍然显著。色氨酸、蛋氨酸、酪氨酸、天冬酰胺、C14:0鞘磷脂和1-甲基烟酰胺水平较低，以及葡糖醛酸、N-氨甲酰基-β-丙氨酸、异柠檬酸、肌酐、C4-羟基肉碱、胱硫醚、羟基苯乙酸和腐胺水平较高，与更虚弱的SAVE评分相关。通路分析确定了氮代谢、氨酰-tRNA生物合成和柠檬酸循环。未来的研究需要证实这些与SAVE相关的代谢物和途径，它们可能揭示了身体虚弱综合征中涉及的新机制。
