Abstract

This competitive renewal seeks support to continue our work on a-adrenergic modulation of resting and acute food-intake related energy expenditure (EE) with primary human aging. In the first set of specific aims we propose to establish the integrative sympathoadrena1 a-adrenergic mechanisms responsible for the reductions in body composition-adjusted resting metabolic rate (RMRadj) and the thermic effect of food (TEF-the postprandial increase in EE in response to acute energy intake) that occur with advancing age. In the second set of specific aims we propose to determine the integrative sympathoadrenal a-adrenergic mechanisms responsible for the greater RMRadj: and TEF in habitually exercising vs. sedentary middle-aged and older adults?In the third set of specific aims we propose to determine the role of a2-adrenergic receptor gene variants in explaining inter-individual differences in a-adrenergic modulation of RMRadj and TEF in general, and specifically with advancing age. To test these hypotheses and achieve the associated specific aims we will use a novel translational experimental approach that attempts to link age- and habitual exercise-related group differences in EE (RMRadj;TEF) with systemic (tonic a-adrenergic modulation of metabolic rate;a-adrenergic stimulation of postprandial thermogenesis;sympathoadrenal system activity;metabolic responsiveness to a- adrenergic stimulation), cellular/molecular (a-adrenergic receptor and post-receptor signaling properties), and genetic (a2-adrenergic receptor gene variants) in healthy adult humans. The proposed research should provide new and clinically important insight into the separate and interactive effects of aging and habitual exercise on a- adrenergic modulation of EE, with important implications for the prevention of age-associated obesity. The proposed research also will provide novel insight into the integrative (whole-body to molecular/genetic) physiological mechanisms underlying these effects.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG015897-10
Application #
7572854
Study Section
Special Emphasis Panel (ZRG1-ASG (01))
Program Officer
Dutta, Chhanda
Project Start
2000-02-01
Project End
2012-01-31
Budget Start
2009-05-15
Budget End
2012-01-31
Support Year
10
Fiscal Year
2009
Total Cost
$266,341
Indirect Cost

  Institution

Name
University of Colorado at Boulder
Department
Physiology
Type
Schools of Arts and Sciences
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309

  Publications

Christou, Demetra D; Pierce, Gary L; Walker, Ashley E et al. (2012) Vascular smooth muscle responsiveness to nitric oxide is reduced in healthy adults with increased adiposity. Am J Physiol Heart Circ Physiol 303:H743-50
Jablonski, Kristen L; Chonchol, Michel; Pierce, Gary L et al. (2011) 25-Hydroxyvitamin D deficiency is associated with inflammation-linked vascular endothelial dysfunction in middle-aged and older adults. Hypertension 57:63-9
Gano, Lindsey B; Donato, Anthony J; Pierce, Gary L et al. (2011) Increased proinflammatory and oxidant gene expression in circulating mononuclear cells in older adults: amelioration by habitual exercise. Physiol Genomics 43:895-902
Walker, Ashley E; Seibert, Sara Marian; Donato, Anthony J et al. (2010) Vascular endothelial function is related to white blood cell count and myeloperoxidase among healthy middle-aged and older adults. Hypertension 55:363-9
LaRocca, Thomas J; Seals, Douglas R; Pierce, Gary L (2010) Leukocyte telomere length is preserved with aging in endurance exercise-trained adults and related to maximal aerobic capacity. Mech Ageing Dev 131:165-7
Seals, Douglas R; Walker, Ashley E; Pierce, Gary L et al. (2009) Habitual exercise and vascular ageing. J Physiol 587:5541-9
Lesniewski, Lisa A; Connell, Melanie L; Durrant, Jessica R et al. (2009) B6D2F1 Mice are a suitable model of oxidative stress-mediated impaired endothelium-dependent dilation with aging. J Gerontol A Biol Sci Med Sci 64:9-20
Pierce, Gary L; Lesniewski, Lisa A; Lawson, Brooke R et al. (2009) Nuclear factor-{kappa}B activation contributes to vascular endothelial dysfunction via oxidative stress in overweight/obese middle-aged and older humans. Circulation 119:1284-92
Stob, Nicole R; Seals, Douglas R; Jorgen, Jensen et al. (2007) Increased thermogenic responsiveness to intravenous beta-adrenergic stimulation in habitually exercising humans is not related to skeletal muscle beta2-adrenergic receptor density. Exp Physiol 92:823-30
Stob, Nicole R; Bell, Christopher; van Baak, Marleen A et al. (2007) Thermic effect of food and beta-adrenergic thermogenic responsiveness in habitually exercising and sedentary healthy adult humans. J Appl Physiol 103:616-22

Showing the most recent 10 out of 17 publications