Human Aging and B-adrenergic Modulation of Thermogenesis

人类衰老和 B 肾上腺素能对产热的调节

• 批准号: 7572854
• 负责人: DOUGLAS R SEALS
• 金额: $ 26.63万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7572854
• 关键词: Accounting; Acute; Adenylate Cyclase; Adipose tissue; Adrenergic Agents; Adrenergic Agonists; Adrenergic Receptor; Adult; Affinity; Age; Aging; Agonist; Alleles; Area; Basal metabolic rate; Body Composition; Catecholamines; Chronic; Clinical; Disease; Eating; Elderly; Energy Intake; Energy Metabolism; Exercise; Expenditure; Exposure to; Food; Genetic; Genetic Determinism; Genetic Variation; Human; Individual; Individual Differences; Intervention; Isoproterenol; Link; Measures; Mediating; Metabolic; Molecular; Molecular Genetics; Obesity; Physiological; Placebo Control; Plasma; Prevention; Property; Receptor Activation; Receptor Gene; Receptor Signaling; Regulation; Research; Resources; Rest; Role; Signal Pathway; Signal Transduction; Skeletal Muscle; Stimulus; Sympathetic Nervous System; System; Testing; Thermogenesis; Variant; Very Light Exercise; Withdrawal; Woman; Work; adrenergic; age effect; base; desensitization; insight; men; middle age; novel; older men; receptor density; response; sedentary

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：这种竞争性更新寻求支持，以继续我们对与初级人类衰老的静息和急性食品相关能量支出（EE）进行A肾上腺素能调节的工作。 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.在第二组具体目的中，我们建议确定负责较大的rmradj的综合交感神经A-肾上腺素机制：在习惯性地行使与久坐的中年和老年人中，在第三组特定目标中，我们建议我们在解释A2-辅助受体基因变化中的作用方面的作用，从而互相差异，以构建差异。总体上，特别是随着年龄的增长。为了检验这些假设并实现相关的特定目的，我们将使用一种新型的翻译实验方法，该方法试图将EE年龄和习惯性运动相关的群体差异（rmradj; tef）与全身性的（补体A-肾上腺素能调节）的代谢速度； A-辅助性刺激的辅助性刺激；辅助性刺激A a-sypthial-Systement; sypatherric in-Pathorencation;健康成年人的细胞/分子（A-肾上腺素能受体和受体信号传导特性）以及遗传（A2-肾上腺素能受体基因变异）。拟议的研究应为衰老和习惯运动对EE的肾上腺素能调节的单独和互动效应提供新的和临床上重要的见解，对预防与年龄相关的肥胖具有重要意义。拟议的研究还将提供有关这些作用背后的综合性（分子/遗传）生理机制的新颖见解。