The kynurenine pathway in HIV, frailty and inflammaging

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, osteo...

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Published inFrontiers in immunology Vol. 14; p. 1244622
Main Authors Sultana, Shabiha, Elengickal, Anthony, Bensreti, Husam, de Chantemèle, Eric Belin, McGee-Lawrence, Meghan E., Hamrick, Mark W.
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 08.09.2023
Subjects
Aged
aryl hydrocarbon receptor
Cytokines
Frailty
HIV Infections - drug therapy
Humans
IDO1
Immunology
inflammation
Kynurenine
osteoporosis
sarcopenia
Tryptophan
osteoporosis
inflammation
IDO1
aryl hydrocarbon receptor
sarcopenia
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Abstract 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.
AbstractList 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.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.
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.
Author Sultana, Shabiha
Bensreti, Husam
de Chantemèle, Eric Belin
McGee-Lawrence, Meghan E.
Hamrick, Mark W.
Elengickal, Anthony
AuthorAffiliation Medical College of Georgia, Augusta University , Augusta, GA , United States
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Copyright Copyright © 2023 Sultana, Elengickal, Bensreti, de Chantemèle, McGee-Lawrence and Hamrick.
Copyright © 2023 Sultana, Elengickal, Bensreti, de Chantemèle, McGee-Lawrence and Hamrick 2023 Sultana, Elengickal, Bensreti, de Chantemèle, McGee-Lawrence and Hamrick
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Keywords osteoporosis
inflammation
IDO1
aryl hydrocarbon receptor
sarcopenia
Language English
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Snippet Kynurenine (Kyn) is a circulating tryptophan (Trp) catabolite generated by enzymes including IDO1 that are induced by inflammatory cytokines such as...
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SubjectTerms Aged
aryl hydrocarbon receptor
Cytokines
Frailty
HIV Infections - drug therapy
Humans
IDO1
Immunology
inflammation
Kynurenine
osteoporosis
sarcopenia
Tryptophan
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Title The kynurenine pathway in HIV, frailty and inflammaging
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