Frailty is a state in geriatrics where individuals have age-associated decline and increased vulnerability to multiple physiological systems. Individuals with neuromuscular function decline with associated sarcopenia have a greater incidence of hip fractures, increasing their risk of death. Recent studies have shown kynurenine pathway alterations in other age-related diseases including neurodegenerative disorders. Therefore, it is not surprising that frail adults also have alterations in KP metabolite levels including increased 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN) (Westbrook et al., 2020). You can learn more about the kynurenine pathway and frailty from one of our previous keynote speakers, Prof Gustavo Duque in here (members only).
Since QUIN has been shown to be a neurotoxic metabolite, Dr. Tae Chung and colleagues wanted to further investigate its role in frailty. This follow-up study used an aging quinolinate phosphoribosyl transferase (QPRT) knock-out mouse model. QPRT null mice have increased QUIN levels in the brain compared to wild type mice making this model ideal for testing the impact that QUIN plays in neuromuscular decline. Here the authors show that QUIN is also elevated in the spinal cord of these mice. Aged male QPRT knock out animals had increased frailty scores compared to control animals which was not observed in females. Forelimb grip strength was significantly reduced in the aged QPRT null male mice. Additionally, neuromuscular denervation was shown in QRPT null animals, starting around 11-13 months of age. Taken together, motor neurons chronically exposed to QUIN may lead to degeneration and play a role in neuromuscular decline. Further research is needed to understand the overall impact that QUIN and the activity of the KP have on frailty.