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.