The candidate is a new investigator at Colorado State University (CSU). The candidate's long-term goal is to obtain independent funding to develop a research laboratory that uses an integrative and translational approach to investigate the interaction of energy and protein metabolism and their roles in the healthy aging of skeletal muscle. The immediate career goal is to obtain a protected period of research to develop skills for the assessment of potential tissue-specific mitochondrial turnover to changes in energy and with aging. Specifically, the proposed project addresses the protein turnover and mitochondrial theories of aging, and challenges the paradigm that protein turnover increases during periods of energy restriction (ER). The project will examine short and long- term changes in mitochondria turnover by redundant measurements to complete a comprehensive assessment of turnover. It is proposed that changes in mitochondria turnover will be mediated at the step of translation, since translation is an energetically expensive process. The mTOR and PGC-lot pathways, as well as AMPK activation will be explored as mediators of transcription and translation. The current proposal exploits the applicant's experience with stable isotopic tracers although new methods will be learned in the laboratory of Dr. Marc Hellerstein (UC-Berkeley, key consultant). Significant training aspects will be directed by Dr. Greg Cartee (University of Michigan, co-mentor) and Dr. Michael Pagliassotti (CSU, co- mentor) with instruction on the use of laboratory animals, ER methodology, tissue isolation techniques, and studies of cellular signaling. Study design, oversight and professional mentorship in aging research will be provided by Dr. Manfred Diehl (CSU, Director of the Center on Aging, co-mentor).

Public Health Relevance

Mitochondria deterioration has been proposed as causative to age-related decline in function. The current proposal seeks to understand how acute feeding, energy status (energy restricted (ER) or adequately fed), and tissue location effect age-induced changes in mitochondria turnover. It is hoped that the understanding of these processes will aid in safe and effective strategies for successful aging.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AG031829-05
Application #
8423764
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Finkelstein, David B
Project Start
2009-03-15
Project End
2014-02-28
Budget Start
2013-04-01
Budget End
2014-02-28
Support Year
5
Fiscal Year
2013
Total Cost
$122,364
Indirect Cost
$9,064
Name
Colorado State University-Fort Collins
Department
Type
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Drake, Joshua C; Bruns, Danielle R; Peelor 3rd, Frederick F et al. (2014) Long-lived crowded-litter mice have an age-dependent increase in protein synthesis to DNA synthesis ratio and mTORC1 substrate phosphorylation. Am J Physiol Endocrinol Metab 307:E813-21
Miller, Benjamin F; Drake, Joshua C; Naylor, Bradley et al. (2014) The measurement of protein synthesis for assessing proteostasis in studies of slowed aging. Ageing Res Rev 18:106-11
Kennedy, Amy L; Nelson, Tracy; Pettine, Stefan et al. (2014) Medication use following bariatric surgery: factors associated with early discontinuation. Obes Surg 24:696-704
Schmidt, Stacy L; Bessesen, Daniel H; Stotz, Sarah et al. (2014) Adrenergic control of lipolysis in women compared with men. J Appl Physiol (1985) 117:1008-19
Miller, Benjamin F; Robinson, Matthew M; Reuland, Danielle J et al. (2013) Calorie restriction does not increase short-term or long-term protein synthesis. J Gerontol A Biol Sci Med Sci 68:530-8
Miller, Benjamin F; Hamilton, Karyn L (2012) A perspective on the determination of mitochondrial biogenesis. Am J Physiol Endocrinol Metab 302:E496-9
Miller, Benjamin F; Robinson, Matthew M; Bruss, Matthew D et al. (2012) A comprehensive assessment of mitochondrial protein synthesis and cellular proliferation with age and caloric restriction. Aging Cell 11:150-61
Robinson, Matthew M; Bell, Christopher; Peelor 3rd, Frederick F et al. (2011) ?-Adrenergic receptor blockade blunts postexercise skeletal muscle mitochondrial protein synthesis rates in humans. Am J Physiol Regul Integr Comp Physiol 301:R327-34
Jordan, Leora Y; Melanson, Edward L; Melby, Christopher L et al. (2010) Nitrogen balance in older individuals in energy balance depends on timing of protein intake. J Gerontol A Biol Sci Med Sci 65:1068-76