This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DHEA declines dramatically with age. Low DHEA levels have been found to correlate with sarcopenia and osteopenia. It is therefore postulated that many physiologic changes of aging are secondary to the decline in DHEA. Thus the objective of the proposed research is to evaluate the effect of DHEA replacement on age-related changes in body composition, muscle function and metabolism, and bone mass in healthy older adults.
The specific aims are to evaluate the effects of 10 months of DHEA replacement (50 mg/d) in combination with resistance exercise training on a) total body fat content and lean body mass, intra-abdominal fat volume and thigh muscle area, and muscle protein turnover and synthesis ; b) bone mineral density of the total body, lumbar spine and hip and biochemical markers of bone turnover; and c) insulin sensitivity. Muscle protein synthesis rate will be determined by the incorporation rate of 13C-leucine into skeletal muscle proteins. GC/quadrupole/MS and GC/combustion/MS will be used to quantify 13C-leucine abundance in plasma, muscle free amino acids, and structural muscle proteins. It is hypothesized that DHEA administration will increase muscle and bone mass, decrease visceral fat mass, and increase insulin sensitivity and that these effects will be additive or synergistic with exercise. Healthy but sedentary subjects, aged 65-78 yr. old will be randomized to receive either DHEA, 50 mg/d for ten months. All participants will participate in supervised exercise training programs for four months. The supervised exercise program will consist of resistance training designed to increase muscle mass, strength, and bone mass, and decrease fat mass. The goal of this research is to provide information on the potential role of DHEA replacement therapy in maintaining the physical health and functional capacity of older people.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000954-29
Application #
7355188
Study Section
Special Emphasis Panel (ZRG1-BPC-H (40))
Project Start
2006-02-01
Project End
2007-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
29
Fiscal Year
2006
Total Cost
$5,897
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Yue, Xuyi; Dhavale, Dhruva D; Li, Junfeng et al. (2018) Design, synthesis, and in vitro evaluation of quinolinyl analogues for ?-synuclein aggregation. Bioorg Med Chem Lett 28:1011-1019
Lin, Xiaobo; Racette, Susan B; Ma, Lina et al. (2017) Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans. Arterioscler Thromb Vasc Biol 37:2364-2369
Ovod, Vitaliy; Ramsey, Kara N; Mawuenyega, Kwasi G et al. (2017) Amyloid ? concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement 13:841-849
Cade, W Todd; Levy, Philip T; Tinius, Rachel A et al. (2017) Markers of maternal and infant metabolism are associated with ventricular dysfunction in infants of obese women with type 2 diabetes. Pediatr Res 82:768-775
Lucey, Brendan P; Mawuenyega, Kwasi G; Patterson, Bruce W et al. (2017) Associations Between ?-Amyloid Kinetics and the ?-Amyloid Diurnal Pattern in the Central Nervous System. JAMA Neurol 74:207-215
Ohlemacher, Shannon I; Giblin, Daryl E; d'Avignon, D André et al. (2017) Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria. J Clin Invest 127:4018-4030
Wei, Xiaochao; Song, Haowei; Yin, Li et al. (2016) Fatty acid synthesis configures the plasma membrane for inflammation in diabetes. Nature 539:294-298
Shields-Cutler, Robin R; Crowley, Jan R; Miller, Connelly D et al. (2016) Human Metabolome-derived Cofactors Are Required for the Antibacterial Activity of Siderocalin in Urine. J Biol Chem 291:25901-25910
Mertins, Philipp; Mani, D R; Ruggles, Kelly V et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534:55-62
Murata, Takahiro; Dietrich, Hans H; Horiuchi, Tetsuyoshi et al. (2016) Mechanisms of magnesium-induced vasodilation in cerebral penetrating arterioles. Neurosci Res 107:57-62

Showing the most recent 10 out of 696 publications