Kynurenine induces an age-related phenotype in bone marrow stromal cells

Dhara Patel, Matthew Potter, Jordan Marcano Anaya, Meghan E. McGee-Lawrence, Mark W. Hamrick, William D Hill, Carlos M Isales, Sadanand T Fulzele

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number111464
JournalMechanisms of Ageing and Development
Volume195
DOIs
StatePublished - Apr 2021

Keywords

  • Aging
  • Bone marrow stromal cells
  • Kynurenine

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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