A Study of Wnt and Notch Signaling in the Muscle Stem Cells of Accelerated-aging Mouse Model

INTRODUCTION: Over the last few years, the study of mouse model of progeria in which certain aspects of aging are manifested has expanded our knowledge of the molecular basis of aging. Such mouse models of accelerated-aging include XPF-ERCC1 deficient (ERCC-/Δ) mice, and Zmpste24 deficient mice (Z24-/-). Both of these mouse models demonstrate spontaneous premature onset of aging-related changes. The process of myogenic differentiation was reported to be regulated by an antagonistic balance between active Notch and Wnt/β-catenin signaling pathways, which both has been indicated to play important role in regulating stem cell proliferation and differentiation, and the regeneration of skeletal muscle (1, 2). Notch signaling was shown to potently repress myogenesis by affecting the function of MyoD and other myogenic factors (3, 4). In late stages of regeneration, a switch from Notch to Wnt signaling in muscle stem cells is necessary for normal myogenesis (2). Meanwhile, Wnt signaling was found to increase during aging and alter muscle stem cell fate and increases fibrosis (5), while Notch signaling was found to decrease during aging and contributes to a declined response of muscle stem cell to injury (2). However, the regulatory mechanism of Wnt and Notch signaling in the muscle derived stem cells (MDSCs) from mouse model of progeria is not know yet, and the current study has been conducted to provide more details in this field.