Date of Award

12-1-2016

Degree Name

Master of Science

Department

Molecular Biology Microbiology and Biochemistry

First Advisor

Yuan, Rong

Second Advisor

Ran, Sophia

Abstract

Previous studies have found Nrip1 as a novel aging related gene. Global deletion of Nrip1 in mice can benefit systematic metabolism. For example, enhanced resistance to high fat diet-induced obesity, lower body weight, leaner body composition, increased insulin sensitivity, enhanced mitochondrial biogenesis and increased longevity in female. At the same time deletion of Nrip1 has negative effects for metabolism, like infertile in female and impaired memory. With these facts, we decided to invested the function of Nrip1 in a tissue specific manner to maximize the positive effects of Nrip1 in aging. To select the tissue target of knocking out Nrip1, I carried out a systematic study to measure the expression of Nrip1 expression in aging process and under diet restriction condition. From these results, we generated liver, white adipose tissue and skeletal muscle specific knockout mice model. My project focused on the skeletal muscle specific Nrip1 knockout model. Results showing, skeletal muscle specific deletion of Nrip1 can increase lean body weight in female, reduce insulin sensitivity and suggestively increase circulating IGF1. Longevity study showing skeletal muscle specific knockout Nrip1 can shorten longevity in male mice but showing no difference in female. The cellular and molecular studies in Nrip1 knockout mouse embryonic fibroblast and global knockout mice indicating the effects of Nrip1 on aging and longevity might be related to the regulation of pro-inflammation, cell senescence and cell growth, as well as autophagy.

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