Ahmed Al Saedi, Sharron Chow, Sara Vogrin, Gilles J Guillemin, Gustavo Duque
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In this study, we quantified 7 KP metabolites, including kynurenine (KYN), kynurenine acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), and anthranilic acid (AA) using ultra-high-performance liquid chromatography and gas chromatography-mass spectrometry in the serum of 85 participants (median age 75; 65% female; 28 non-frail, 29 pre-frail, and 28 frail) at the Nepean Osteoporosis and Frailty (NOF) Study. We looked at the association between TRP metabolites and physical performance, sarcopenia, and frailty. After adjusting for age and sex, our results showed that KYN and KYN/TRP were associated with higher interleukin (IL)-6 levels (<i>r</i> = .324 and <i>r</i> = .390, respectively). KYNA and its ratios to other products (mainly KYNA/KYN, KYNA/QUIN, and KYNA/PIC) were associated with a lower likelihood of frailty by Fried's criteria (OR 0.93 [0.88, 0.98], <i>P</i> = .009) and Rockwood index (<i>r</i> = -.241, <i>P</i> = .028) as well as a lower likelihood of sarcopenia (OR 0.88 [0.78, 1.00], <i>P</i> = .049). QUIN and QUIN/KYN showed an association with increased IL-6 (<i>r</i> = .293 and .204 respectively), higher likelihood of frailty (OR 1.02 [1.00, 1.04], <i>P</i> = .029 and OR 6.43 [2.23, 18.51], <i>P</i> = .001 respectively) and lower physical function (<i>r</i> = -.205 and <i>r</i> = -.292). In conclusion, different TRP metabolites have various associations with physical performance, frailty, and sarcopenia. Defining the underlying mechanisms may permit the development and validation of new biomarkers and therapeutics for frailty and musculoskeletal conditions targeting specific metabolites of the TRP catabolic pathway.</p>","PeriodicalId":520654,"journal":{"name":"International journal of tryptophan research : IJTR","volume":" ","pages":"11786469211069951"},"PeriodicalIF":4.1000,"publicationDate":"2022-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a9/2f/10.1177_11786469211069951.PMC8808031.pdf","citationCount":"5","resultStr":"{\"title\":\"Association Between Tryptophan Metabolites, Physical Performance, and Frailty in Older Persons.\",\"authors\":\"Ahmed Al Saedi, Sharron Chow, Sara Vogrin, Gilles J Guillemin, Gustavo Duque\",\"doi\":\"10.1177/11786469211069951\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Frailty is defined as a syndrome of physiological decline in late life, characterized by marked vulnerability to adverse health outcomes. A robust biomarker for frailty is still lacking. Tryptophan (TRP) metabolism through the kynurenine pathway (KP) plays essential roles in aging, the musculoskeletal system, and physical performance. In this study, we quantified 7 KP metabolites, including kynurenine (KYN), kynurenine acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), and anthranilic acid (AA) using ultra-high-performance liquid chromatography and gas chromatography-mass spectrometry in the serum of 85 participants (median age 75; 65% female; 28 non-frail, 29 pre-frail, and 28 frail) at the Nepean Osteoporosis and Frailty (NOF) Study. We looked at the association between TRP metabolites and physical performance, sarcopenia, and frailty. After adjusting for age and sex, our results showed that KYN and KYN/TRP were associated with higher interleukin (IL)-6 levels (<i>r</i> = .324 and <i>r</i> = .390, respectively). KYNA and its ratios to other products (mainly KYNA/KYN, KYNA/QUIN, and KYNA/PIC) were associated with a lower likelihood of frailty by Fried's criteria (OR 0.93 [0.88, 0.98], <i>P</i> = .009) and Rockwood index (<i>r</i> = -.241, <i>P</i> = .028) as well as a lower likelihood of sarcopenia (OR 0.88 [0.78, 1.00], <i>P</i> = .049). QUIN and QUIN/KYN showed an association with increased IL-6 (<i>r</i> = .293 and .204 respectively), higher likelihood of frailty (OR 1.02 [1.00, 1.04], <i>P</i> = .029 and OR 6.43 [2.23, 18.51], <i>P</i> = .001 respectively) and lower physical function (<i>r</i> = -.205 and <i>r</i> = -.292). In conclusion, different TRP metabolites have various associations with physical performance, frailty, and sarcopenia. 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引用次数: 5
摘要
虚弱被定义为晚年生理衰退的一种综合征，其特点是明显易受不利健康结果的影响。目前仍缺乏一种强有力的脆弱生物标志物。色氨酸(TRP)通过犬尿氨酸途径(KP)代谢在衰老、肌肉骨骼系统和身体表现中起着至关重要的作用。在这项研究中，我们使用超高效液相色谱和气相色谱-质谱法定量了85名参与者(中位年龄75岁;65%的女性;在Nepean骨质疏松和虚弱(NOF)研究中，28名非虚弱者，29名前期虚弱者和28名虚弱者。我们研究了TRP代谢物与身体表现、肌肉减少症和虚弱之间的关系。在调整了年龄和性别后，我们的结果显示KYN和KYN/TRP与较高的白细胞介素(IL)-6水平相关(r =。和r =。390年,分别)。根据Fried标准(OR 0.93 [0.88, 0.98]， P = 0.009)和Rockwood指数(r = -)， KYNA及其与其他产品(主要是KYNA/KYN、KYNA/QUIN和KYNA/PIC)的比值与较低的衰弱可能性相关。241, P = 0.028)，肌肉减少症的可能性较低(OR 0.88 [0.78, 1.00]， P = 0.049)。QUIN和QUIN/KYN与IL-6升高相关(r =。(分别为0.293和0.204)，体质虚弱的可能性较高(OR 1.02 [1.00, 1.04]， P = 0.99)。029和OR 6.43 [2.23, 18.51]， P =。001)和较低的物理功能(r = -。205, r = - 0.292)。总之，不同的色氨酸代谢物与体能、虚弱和肌肉减少症有不同的关联。确定潜在的机制可能允许开发和验证针对TRP分解代谢途径的特定代谢物的新的生物标志物和治疗虚弱和肌肉骨骼疾病的疗法。
Association Between Tryptophan Metabolites, Physical Performance, and Frailty in Older Persons.
Frailty is defined as a syndrome of physiological decline in late life, characterized by marked vulnerability to adverse health outcomes. A robust biomarker for frailty is still lacking. Tryptophan (TRP) metabolism through the kynurenine pathway (KP) plays essential roles in aging, the musculoskeletal system, and physical performance. In this study, we quantified 7 KP metabolites, including kynurenine (KYN), kynurenine acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), and anthranilic acid (AA) using ultra-high-performance liquid chromatography and gas chromatography-mass spectrometry in the serum of 85 participants (median age 75; 65% female; 28 non-frail, 29 pre-frail, and 28 frail) at the Nepean Osteoporosis and Frailty (NOF) Study. We looked at the association between TRP metabolites and physical performance, sarcopenia, and frailty. After adjusting for age and sex, our results showed that KYN and KYN/TRP were associated with higher interleukin (IL)-6 levels (r = .324 and r = .390, respectively). KYNA and its ratios to other products (mainly KYNA/KYN, KYNA/QUIN, and KYNA/PIC) were associated with a lower likelihood of frailty by Fried's criteria (OR 0.93 [0.88, 0.98], P = .009) and Rockwood index (r = -.241, P = .028) as well as a lower likelihood of sarcopenia (OR 0.88 [0.78, 1.00], P = .049). QUIN and QUIN/KYN showed an association with increased IL-6 (r = .293 and .204 respectively), higher likelihood of frailty (OR 1.02 [1.00, 1.04], P = .029 and OR 6.43 [2.23, 18.51], P = .001 respectively) and lower physical function (r = -.205 and r = -.292). In conclusion, different TRP metabolites have various associations with physical performance, frailty, and sarcopenia. Defining the underlying mechanisms may permit the development and validation of new biomarkers and therapeutics for frailty and musculoskeletal conditions targeting specific metabolites of the TRP catabolic pathway.
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