TY - JOUR
T1 - Kynurenine induces an age-related phenotype in bone marrow stromal cells
AU - Patel, Dhara
AU - Potter, Matthew
AU - Anaya, Jordan Marcano
AU - McGee-Lawrence, Meghan E.
AU - Hamrick, Mark W.
AU - Hill, William D.
AU - Isales, Carlos M.
AU - Fulzele, Sadanand
N1 - Funding Information:
This publication is based upon work supported in part by the National Institutes of Health AG036675 (National Institute on Aging-AG036675 S.F, MML., W.D.H., M.H., C.S.,) and R56AG062647 (S.F.). The funding mentioned above did not lead to any conflict of interest regarding the publication of this manuscript.
Funding Information:
This publication is based upon work supported in part by the National Institutes of HealthAG036675 (National Institute on Aging-AG036675 S.F, MML., W.D.H., M.H., C.S.,) and R56AG062647 (S.F.). The funding mentioned above did not lead to any conflict of interest regarding the publication of this manuscript.
Publisher Copyright:
© 2021
PY - 2021/4
Y1 - 2021/4
N2 - Advanced age is one of the important contributing factors for musculoskeletal deterioration. Although the exact mechanism behind this degeneration is unknown, it has been previously established that nutritional signaling plays a vital role in musculoskeletal pathophysiology. Our group established the vital role of the essential amino acid, tryptophan, in aging musculoskeletal health. With advanced age, inflammatory factors activate indoleamine 2,3-dioxygenase (IDO1) and accumulate excessive intermediate tryptophan metabolites such as Kynurenine (KYN). With age, Kynurenine accumulates and suppresses osteogenic differentiation, impairs autophagy, promotes early senescence, and alters cellular bioenergetics of bone marrow stem cells. Recent studies have shown that Kynurenine negatively impacts bone marrow stromal cells (BMSCs) and, consequently, promotes bone loss. Overall, understanding the mechanism behind BMSCs losing their ability for osteogenic differentiation can provide insight into the prevention of osteoporosis and the development of targeted therapies. Therefore, in this article, we review Kynurenine and how it plays a vital role in BMSC dysfunction and bone loss with age.
AB - Advanced age is one of the important contributing factors for musculoskeletal deterioration. Although the exact mechanism behind this degeneration is unknown, it has been previously established that nutritional signaling plays a vital role in musculoskeletal pathophysiology. Our group established the vital role of the essential amino acid, tryptophan, in aging musculoskeletal health. With advanced age, inflammatory factors activate indoleamine 2,3-dioxygenase (IDO1) and accumulate excessive intermediate tryptophan metabolites such as Kynurenine (KYN). With age, Kynurenine accumulates and suppresses osteogenic differentiation, impairs autophagy, promotes early senescence, and alters cellular bioenergetics of bone marrow stem cells. Recent studies have shown that Kynurenine negatively impacts bone marrow stromal cells (BMSCs) and, consequently, promotes bone loss. Overall, understanding the mechanism behind BMSCs losing their ability for osteogenic differentiation can provide insight into the prevention of osteoporosis and the development of targeted therapies. Therefore, in this article, we review Kynurenine and how it plays a vital role in BMSC dysfunction and bone loss with age.
KW - Aging
KW - Bone marrow stromal cells
KW - Kynurenine
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U2 - 10.1016/j.mad.2021.111464
DO - 10.1016/j.mad.2021.111464
M3 - Review article
C2 - 33631183
AN - SCOPUS:85101924188
SN - 0047-6374
VL - 195
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
M1 - 111464
ER -