Journal
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
Volume 75, Issue 5, Pages 849-857Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glz113
Keywords
Protein synthesis; Proteomics; Deuterium oxide; Mouse; Metabolism
Categories
Funding
- National Institutes of Health [R01 AG042569, R00 AG51661, T32 AG052363]
- Oklahoma Nathan Shock Center of Excellence in the Basic Biology of Aging
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17 alpha-Estradiol (17 alpha-E2) is a non-feminizing estrogen that extends life span in male, but not female, mice. We recently reported that 17 alpha-E2 had robust beneficial effects on metabolic and inflammatory parameters in aged male mice. However, it remains unclear if 17 alpha-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 17 alpha-E2 treated male mice with the hypothesis that 17 alpha-E2 would increase protein synthesis for somatic maintenance. 17 alpha-E2 had no effect on protein synthesis or DNA synthesis in multiple tissues, including white adipose tissue. 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 17 alpha-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, 17 alpha-E2 and CR treatments elicit distinctly different proteostatic outcomes.
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