Association Between Tryptophan Metabolites, Physical Performance, and Frailty in Older Persons

Ahmed Al Saedi; Sharron Chow; Sara Vogrin; Gilles J Guillemin; Gustavo Duque

doi:10.1177/11786469211069951

Association Between Tryptophan Metabolites, Physical Performance, and Frailty in Older Persons

Int J Tryptophan Res. 2022 Jan 31:15:11786469211069951. doi: 10.1177/11786469211069951. eCollection 2022.

Authors

Ahmed Al Saedi^{1

2}, Sharron Chow³, Sara Vogrin^{1

2}, Gilles J Guillemin³, Gustavo Duque^{1

2}

Affiliations

¹ Australian Institute for Musculoskeletal Science (AIMSS), Geroscience & Osteosarcopenia Research Program, The University of Melbourne and Western Health, St. Albans, VIC, Australia.
² Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, St. Albans, VIC, Australia.
³ Neuroinflammation Group, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.

Abstract

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.

Keywords: Tryptophan; frailty; kynurenine; osteosarcopenia; sarcopenia.