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J Gerontol A Biol Sci Med Sci. 2019 May 10. pii: glz113. doi: 10.1093/gerona/glz113. [Epub ahead of print]

Short-term calorie restriction and 17α-estradiol administration elicit divergent effects on proteostatic processes and protein content in metabolically active tissues.

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Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Health and Exercise Science Department, Colorado State University, Fort Collins, CO, USA.
Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Oklahoma City Veterans Affairs Medical Center, Oklahoma City, OK, USA.
Department of Nutritional Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.


17α-estradiol (17α-E2) is a 'non-feminizing' estrogen that extends lifespan in male, but not female, mice. We recently reported that 17α-E2 had robust beneficial effects on metabolic and inflammatory parameters in aged male mice. However, it remains unclear if 17α-E2 also delays other 'hallmarks' of aging, particularly maintaining proteostasis. Here we used isotope labeling methods in older mice to examine proteostatic mechanisms. We compared weight-matched mild calorie restricted (CR) and 17α-E2 treated male mice with the hypothesis that 17α-E2 would increase protein synthesis for somatic maintenance. 17α-E2 had no effect on protein synthesis or DNA synthesis in multiple tissues, including white adipose tissue (WAT). Conversely, mild short-term CR decreased DNA synthesis and increased the protein to DNA synthesis ratio in multiple tissues. Examination of individual protein synthesis and content did not differentiate treatments although it provided insight into the regulation of protein content between tissues. Contrary to our hypothesis we did not see the predicted differences in protein to DNA synthesis following 17α-E2 treatment. However, mild short-term CR elicited differences consistent with both lifelong CR and other treatments that curtail aging processes. These data indicated that despite similar maintenance of body mass, 17α-E2 and CR treatments elicit distinctly different proteostatic outcomes.


deuterium oxide; metabolism; mouse; proteomics; Protein synthesis


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