Mammalian aging is associated with functional defects in numerous tissues that require replenishment of lost or damaged cells during life. Many observations in the literature provide evidence that stem cells and progenitor cells are altered with advancing age. However, the specific gene pathways that govern stem cell aging and the precise changes that occur in tissue progenitor cells during aging remain to be defined. We will use genetically engineered mice to study specific gene pathways implicated in stem cell aging. These include the Wnt pathway (Projects 1, 2 and 3), the telomerase pathway (Project 2) and the Insulin/Foxo pathway (Project 3). We will investigate stem cell function in several tissues with well defined stem cell populations, including muscle stem cells (Project 1), skin and intestinal stem cells (Project 2) and neural stem cells (Project 3). The Core will support the state-of-the-art mouse genetic approaches which focus on sophisticated loss-of-function studies in vivo using Cre-lox technologies.
The Aims of the Core are:
Specific Aim 1. To generate all the genetically engineered mouse cohorts and controls for analysis of stem cell biology and aging for sharing among the three laboratories of the Program Project.
Specific Aim 2. To provide histology services to support each project including tissue harvesting, fixation and tissue section preparation for analysis among the three laboratories of the Program Project.
Specific Aim 3. To procure and house wild-type mice from the NIA's Aging Mouse Colony for analysis of aging wild-type mice by the three laboratories of the Program Project.
Emerging evidence indicates that altered stem cell function can contribute to human aging. However, the precise changes that occur in stem cells with advancing age and the pathways that govern these changes remain obscure. Investigating the function of three pathways - Wnts, telomerase and Foxo3 - in stem cell biology and aging will greatly enhance our ability to intervene in the aging process..
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