TY - JOUR
T1 - The kynurenine pathway in HIV, frailty and inflammaging
AU - Sultana, Shabiha
AU - Elengickal, Anthony
AU - Bensreti, Husam
AU - de Chantemèle, Eric Belin
AU - McGee-Lawrence, Meghan E.
AU - Hamrick, Mark W.
N1 - Publisher Copyright:
Copyright © 2023 Sultana, Elengickal, Bensreti, de Chantemèle, McGee-Lawrence and Hamrick.
PY - 2023
Y1 - 2023
N2 - Kynurenine (Kyn) is a circulating tryptophan (Trp) catabolite generated by enzymes including IDO1 that are induced by inflammatory cytokines such as interferon-gamma. Kyn levels in circulation increase with age and Kyn is implicated in several age-related disorders including neurodegeneration, osteoporosis, and sarcopenia. Importantly, Kyn increases with progressive disease in HIV patients, and antiretroviral therapy does not normalize IDO1 activity in these subjects. Kyn is now recognized as an endogenous agonist of the aryl hydrocarbon receptor, and AhR activation itself has been found to induce muscle atrophy, increase the activity of bone-resorbing osteoclasts, decrease matrix formation by osteoblasts, and lead to senescence of bone marrow stem cells. Several IDO1 and AhR inhibitors are now in clinical trials as potential cancer therapies. We propose that some of these drugs may be repurposed to improve musculoskeletal health in older adults living with HIV.
AB - Kynurenine (Kyn) is a circulating tryptophan (Trp) catabolite generated by enzymes including IDO1 that are induced by inflammatory cytokines such as interferon-gamma. Kyn levels in circulation increase with age and Kyn is implicated in several age-related disorders including neurodegeneration, osteoporosis, and sarcopenia. Importantly, Kyn increases with progressive disease in HIV patients, and antiretroviral therapy does not normalize IDO1 activity in these subjects. Kyn is now recognized as an endogenous agonist of the aryl hydrocarbon receptor, and AhR activation itself has been found to induce muscle atrophy, increase the activity of bone-resorbing osteoclasts, decrease matrix formation by osteoblasts, and lead to senescence of bone marrow stem cells. Several IDO1 and AhR inhibitors are now in clinical trials as potential cancer therapies. We propose that some of these drugs may be repurposed to improve musculoskeletal health in older adults living with HIV.
KW - IDO1
KW - aryl hydrocarbon receptor
KW - inflammation
KW - osteoporosis
KW - sarcopenia
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U2 - 10.3389/fimmu.2023.1244622
DO - 10.3389/fimmu.2023.1244622
M3 - Review article
C2 - 37744363
AN - SCOPUS:85171872180
SN - 1664-3224
VL - 14
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 1244622
ER -