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 six months DHEA replacement (50 mg/d) alone, or in combination with resistance exercise training on: a) total body fat content and lean body mass [evaluated by dual energy x-ray abosorptiometry (DEXA)], intraabdominal fat volume and thigh muscle area [measured by magnetic resonance imaging (MRI)], and muscle protein synthesis rate (assessed by stable isotopes); b) bone mineral density (BMD) of the total body, lumbar spine, and hip (evaluated by DEXA) and biochemical markers of bone turnover; and c) insulin sensitivity (evaluated by the euglycemic-hyperinsulinemic pancreatic clamp). 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 (60 men and 60 women), aged 65-78 years old, will be randomized to receive either DHEA, 50 mg/d, or placebo and to participate in either supervised or home exercise training programs. 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. It will serve as the basis for future studies of DHEA replacement as potential adjunct to the restoration of functional independence in frail older adults. This research and the proposed career development plan shall provide Dr. Villareal the opportunity to develop his capabilities in conducting patient-oriented research and independence as an investigator.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Mentored Patient-Oriented Research Career Development Award (K23)
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National Center for Research Resources Initial Review Group (RIRG)
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Wilde, David B
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Washington University
Internal Medicine/Medicine
Schools of Medicine
Saint Louis
United States
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Villareal, Dennis T; Miller 3rd, Bernard V; Banks, Marian et al. (2006) Effect of lifestyle intervention on metabolic coronary heart disease risk factors in obese older adults. Am J Clin Nutr 84:1317-23
Villareal, Dennis T; Holloszy, John O (2006) DHEA enhances effects of weight training on muscle mass and strength in elderly women and men. Am J Physiol Endocrinol Metab 291:E1003-8
Villareal, Dennis T; Steger-May, K; Schechtman, K B et al. (2004) Effects of exercise training on bone mineral density in frail older women and men: a randomised controlled trial. Age Ageing 33:309-12
Villareal, Dennis T; Holloszy, John O (2004) Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial. JAMA 292:2243-8
Villareal, Dennis T; Banks, Marian; Siener, Catherine et al. (2004) Physical frailty and body composition in obese elderly men and women. Obes Res 12:913-20
Spina, Robert J; Meyer, Timothy E; Peterson, Linda R et al. (2004) Absence of left ventricular and arterial adaptations to exercise in octogenarians. J Appl Physiol 97:1654-9
Villareal, Dennis T; Grant, Elizabeth; Miller, J Philip et al. (2003) Clinical outcomes of possible versus probable Alzheimer's disease. Neurology 61:661-7
Ehsani, Ali A; Spina, Robert J; Peterson, Linda R et al. (2003) Attenuation of cardiovascular adaptations to exercise in frail octogenarians. J Appl Physiol 95:1781-8
Villareal, Dennis T; Binder, Ellen F; Yarasheski, Kevin E et al. (2003) Effects of exercise training added to ongoing hormone replacement therapy on bone mineral density in frail elderly women. J Am Geriatr Soc 51:985-90
Villareal, Dennis T (2002) Effects of dehydroepiandrosterone on bone mineral density: what implications for therapy? Treat Endocrinol 1:349-57

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