September 1, 2020 at 9:30 pm

Dissertation Defense by Silvana Duran Ortiz, Sept. 11

Silvana Duran-Ortiz, portrait

Silvana Duran-Ortiz (photo by Evan Leonard)

A public dissertation defense by Silvana Duran Ortiz is Friday, Sept. 11, at 10 a.m.

Duran Ortiz is a graduate student in Biological Sciences and Molecular Cellular Biology. Her adviser is Dr. John Kopchick.

Her dissertation is titled “Characterization and Lifespan Assessment of Inducible Growth Hormone Receptor Disrupted Mice at 6 Months of Age.”

Abstract: Reduction in growth hormone (GH) and insulin-like growth factor-1 (IGF-1) can enhance health and extend lifespan. Mice with a germline disruption in the GHR gene (GHRKO) have low levels of IGF-1 and insulin, high levels of GH, are resistant to cancer and diabetes, and hold the record for being the longest-lived laboratory mouse. Despite their healthy phenotype, the GHRKO mice are obese and have decreased body length. In order to determine if disruption of GHR after birth can also extend lifespan, we previously found that disruption of GHR during sexual maturity, at 6 weeks of age (1.5mGHRKO mice), decreases body size, improves insulin sensitivity, and increases maximum female lifespan. However, if a reduction of GH action is to be considered as a potential human therapeutic to extend healthy lifespan, it is important to elucidate the effects of disrupting GH induced signaling at a mature adult age; that is, disruption in adulthood would be more favorable and therapeutically relevant, as it would not affect growth. In the current study, we disrupted GH action at a mature-adult age (6 months) well after sexual maturation. These animals, referred as 6mGHRKO mice, have a normal body-size, with increased adiposity and circulating GH, but decreased IGF-1 levels. Circulating levels of inflammatory markers were unchanged between 6mGHRKO mice and controls. Experiments to evaluate the status of oxidative damage and mTOR activation in liver, skeletal muscle and subcutaneous adipose tissue of male and female 6mGHRKO mice showed a tissue-specificity and sexual dimorphism in these results. Importantly, male and female 6mGHRKO mice showed no change in body length, and mean, median and maximal lifespan were significantly extended in females. In conclusion, disruption of GH action well past sexual maturation produces beneficial effects on insulin sensitivity and aging in mice.

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