INVESTIGATING THE ROLE OF NRIP1 IN SKIN AGING: DEPLETION OF NRIP1 DELAYS SENESCENCE, REDUCES INFLAMMATION AND ENHANCES AUTOPHAGY IN ADIPOCYTES

Author

Skyler Dawnelle Gerber, Southern Illinois University CarbondaleFollow

Date of Award

8-1-2018

Degree Name

Master of Science

Department

Molecular Biology Microbiology and Biochemistry

First Advisor

Ran, Sophia

Abstract

Skin aging is the most easily identifiable type of aging and is characterized by symptoms including wrinkling, pigmentation spots and thinning. The skin is a complex structure made up of many different cells types that form three main layers: the epidermis, dermis and subdermis. Previous studies have focused on the dermis by studying the MMP/Collagen axis to predict the outcomes of skin aging, however, recent studies have targeted the subdermis. The subdermis is composed of subdermal adipocytes that are responsible for the secretion of a variety of pro-inflammatory cytokines. Phenotypes such as accumulated senescent cells, altered lipid accumulation and reduced adipocyte size have also been associated with adipose aging. Previous studies have linked skin aging to metabolic aging by metabolic syndrome, which increases the risk of skin diseases such as psoriasis, alopecia, acne and cancer by reducing adiponectin and insulin sensitivity, and increasing pro-inflammatory cytokine and oxidative stress production. Using gene mapping and bioinformatics analysis, our lab identified NRIP1 as a candidate gene that can regulate the evolutionary theory of aging, which suggests a tradeoff between female reproduction and aging. Nrip1-null mice have reduced body weight, increased insulin sensitivity and longevity in females, however, global depletion also causes infertility and mammary gland dysfunction. Also, NRIP1 is an important metabolic regulator involved in many biological processes such as glycolysis, fatty acid oxidation, mitochondrial biogenesis and oxidative phosphorylation. Our lab uses Nrip1 KO mouse models to test the biological and pathological role of NRIP1 and has found that deletion of Nrip1 extends longevity in female mice. We have also reported that depletion of Nrip1 reduces breast cancer tumor onset and psoriatic-like phenotypes by studying the underlying cellular and molecular mechanisms of inflammation, senescence and autophagy. In the current study, we evaluated the subdermal, visceral and subcutaneous adipose depots from Nrip1 KO mice and have seen reduced senescent accumulation and NFκB/p-NFκB activity. We also seen delayed senescence, reduced pro-inflammatory cytokine production and enhanced autophagy in preadipocytes in vitro.