Department of Medicine, Augusta University, Augusta, GA, United States.
Center for Healthy Aging, Augusta University, Augusta, GA, United States; Universidad Central Del Caribe Laurel, Av. Sta. Juanita, Bayamón, 00960, Puerto Rico, United States.
Mech Ageing Dev. 2021 Apr;195:111464. doi: 10.1016/j.mad.2021.111464. Epub 2021 Feb 22.
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.
年龄增长是肌肉骨骼系统恶化的一个重要影响因素。尽管导致这种退化的确切机制尚不清楚，但已证实营养信号在肌肉骨骼病理生理学中起着至关重要的作用。我们的研究小组已经确定必需氨基酸色氨酸在衰老的肌肉骨骼健康中的重要作用。随着年龄的增长，炎症因子会激活吲哚胺 2,3-双加氧酶（IDO1），并积累过多的中间色氨酸代谢物，如犬尿氨酸（KYN）。随着年龄的增长，犬尿氨酸会积累并抑制成骨细胞分化，损害自噬，促进早期衰老，并改变骨髓间充质干细胞的细胞能量代谢。最近的研究表明，犬尿氨酸会对骨髓基质细胞（BMSCs）产生负面影响，从而导致骨丢失。总的来说，了解 BMSCs 失去成骨分化能力的机制可以深入了解骨质疏松症的预防和靶向治疗的发展。因此，本文综述了犬尿氨酸及其在 BMSC 功能障碍和年龄相关骨丢失中的重要作用。
