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The Role of Kynurenine Pathway Metabolites in the Development of Frailty in Older Adults

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Abstract

Frailty is the main geriatric syndrome, which is closely associated with age-related diseases and aging in general. Being considered the main pathogenetic mechanism of aging, low-grade chronic inflammation potentially contributes to increased degradation of the essential amino acid tryptophan through the kynurenine pathway. Active metabolites of the kynurenine pathway, when accumulated, implement their immunomodulatory, pro-inflammatory and cytotoxic properties, thereby supporting and enhancing the aging process. Over the past decade, data have been collected on the role of an unbalanced kynurenine pathway in the pathogenesis of frailty and age-related diseases. This review summarizes clinical and experimental data on the importance of kynurenine pathway analysis as a valuable tool for risk stratification and prognosis of frailty and age-related diseases.

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  1. Russian Gerontology Research and Clinical Center, Pirogov National Research Medical University, Institute for Aging Research, Moscow, Russia

    V. S. Pykhtina

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Developing the general concept of the review, literature search and analysis, writing the review text were performed by V.S. Pykhtina.

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Abbreviations: 3-HAA, 3-hydroxyanthranilic acid; 3-HK, 3‑hydroxykynurenine; IL-1, interleukin; IL-6, interleukin; TNF-atumor necrosis factor alpha; IDO, indoleamine 2,3-dioxygenase; KYN, kynurenine; KYNA, kynurenic acid; KMO, kynurenine-3-monooxygenase; TDO, tryptophan 2,3-dioxygenase; TRP, tryptophan; QUIN, quinolinic acid; CNS, central nervous system; CKD, chronic kidney disease; IHD ischemic heart disease; CVD, Cardiovascular disease; NAD+, nicotinamide adenine dinucleotide; NADP nicotinamide adenine dinucleotide phosphate; PA, picolinic acid; NMDA, N-methyl-d-aspartate.

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Pykhtina, V.S. The Role of Kynurenine Pathway Metabolites in the Development of Frailty in Older Adults. Adv Gerontol 13, 138–147 (2023). https://doi.org/10.1134/S2079057024600216

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