High-fat diet regulation of cell cycle and senescence
Dungan, Cory Michael
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The combination of high-energy diets and sedentary lifestyles can lead to a reduction in skeletal muscle quality in obese individuals, impacting the body's ability to metabolize and store macronutrients. Additionally, aging associated muscle atrophy perpetuates the metabolic instability already present in older individuals. One possible mechanism for this is through increased cell cycle regulatory protein expression. Cell cycle regulatory proteins regulate the proliferative potential of cells and increases in their expression may cause cells to prematurely senesce. The aim of this study was to determine if cell cycle regulatory proteins p53, p21, p27, and Rb are altered in young and old animals on a high-fat diet. Three-month (young) and 22-month (old) mice were fed a 60% lard diet for 8 (young) and 6 (old) weeks. Mice were then sacrificed under 3% isoflurane anesthesia, where the gastrocnemius was removed, weighed, and frozen in liquid nitrogen. The tissue was later processed in order to obtain total, nuclear, and cytosolic fractions. Nuclear and cytosolic p21 expression was significantly reduced in the young, while nuclear p27 and Rb were dramatically increased. p53 expression was unchanged in the nucleus but was significantly reduced in the cytoplasm in the young mice. There was no significant change in nuclear p53, p21, or p27 expression in old animals but Rb expression was dramatically altered. Cytosolic p21 expression was significantly increased while p53 trended upwards. A high-fat diet significantly alters cell cycle regulatory proteins in both young and old animals suggesting potential mechanisms for reduced muscle function in obesity and aging. Furthermore, our data suggests there is limited ability for change cell cycle regulatory proteins in aged animals even when on a high-fat diet.