Klotho, stem cells, and aging.
Aging is an inevitable and progressive biological process involving dysfunction and eventually destruction of every tissue and organ. This process is driven by a tightly regulated and complex interplay between genetic and acquired factors. Klotho is an antiaging gene encoding a single-pass transmembrane protein, klotho, which serves as an aging suppressor through a wide variety of mechanisms, such as antioxidation, antisenescence, antiautophagy, and modulation of many signaling pathways, including insulin-like growth factor and Wnt. Klotho deficiency activates Wnt expression and activity contributing to senescence and depletion of stem cells, which consequently triggers tissue atrophy and fibrosis. In contrast, the klotho protein was shown to suppress Wnt-signaling transduction, and inhibit cell senescence and preserve stem cells. A better understanding of the potential effects of klotho on stem cells could offer novel insights into the cellular and molecular mechanisms of klotho deficiency-related aging and disease. The klotho protein may be a promising therapeutic agent for aging and aging-related disorders.
Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA ; Department of Nephrology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
Ao
A
Bian
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.
Javier A
JA
Neyra
Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX, USA.
Ming
M
Zhan
Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA ; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.
Ming Chang
MC
Hu
D000375:Aging / Q000235:genetics / Q000502:physiology*; D019588:Aging, Premature / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000090265:Klotho Proteins; D013234:Stem Cells / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*
D005966:Glucuronidase; D000090265:Klotho Proteins
Wnt; aging; cell senescence; klotho; stem cells