AGE AND CONTROL OF HUMAN SKIN BLOOD-FLOW

人类皮肤血流的年龄和控制

• 批准号: 7268780
• 负责人: W. LARRY KENNEY
• 金额: $ 33.51万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7268780
• 关键词: Address; Adrenergic Receptor; Affinity; Age; Age-Years; Aging; Arts; Attenuated; Blood; Blood Vessels; Blood flow; Body Composition; Body Temperature; Cardiovascular system; Characteristics; Classification; Clinical; Condition; Cutaneous; Data; Dose; Efferent Pathways; Elderly; Elderly man; Environment; Equation; Equilibrium; Exhibits; Frequencies; Funding; Heat Losses; Heating; Human; Hypothalamic structure; Incidence; Investigation; Laboratories; Localized; Mediating; Metabolic; Microdialysis; Modeling; Muscle; Nerve; Neurotransmitter Receptor; Neurotransmitters; Norepinephrine; Organ; Outcome; Pathway interactions; Physiological; Purpose; Rate; Reflex action; Relative (related person); Research Personnel; Resistance; Risk; Role; Series; Site; Skin; Skin Aging; Solutions; Stimulus; Stress; System; Techniques; Temperature; Testing; Time; Tissues; Vasodilation; Woman; age difference; age effect; age group; age related; aged; attenuation; base; design; follow-up; heat stimulus; in vivo; men; natural hypothermia; neuromechanism; neuropeptide Y; neurotransmission; noradrenergic; older men; programs; research study; response; sarcopenia; size; vasoconstriction

DESCRIPTION (provided by applicant): This competitive renewal of R01 AG07004 continues our systematic investigations into mechanisms underlying altered thermoregulatory control of skin blood flow (SkappaBF) with primary human aging, and the consequences thereof. Both cutaneous vasodilation (VD) in response to hyperthermic stimuli and cutaneous vasoconstriction (VC) in response to hypothermic stimuliare significantlyattenuated in aged skin. The previous funding cycle involved a systematic investigation of the mechanisms related to altered cutaneous VD in older men and women (briefly summarized in Section C of this proposal). The next sequence of proposed studies is the logical extension of this line of investigation, i.e., examining the mechanisms and consequences of altered cutaneous VC in aged skin, since (1) primary aging is associated with both a larger decrease in core temperature with cold stress and an increased incidence of clinical hypothermia, (2) these untoward outcomes are primarily the result of a relative inability to vasoconstrict the skin vasculature leading to an increased core-to-skin heat transfer, (3) several plausible sites of age-related changes exist in the efferent VC control pathway which have not been tested in vivo. Furthermore, older men and women with a low body mass and lean muscle mass are at ever) greater risk of hypothermia because of the combined effects of reduced VC and decreased core-to-skin thermal resistance. Specific Aims 1-3 examine basic efferent mechanisms of attenuated reflex VC in aged skin at the sympathetic nerve transmission, neurotransmitter/receptor, and end-organ response levels, respectively. These studies make use of new and recently refined techniques that allow for the in vivo examination of age-related changes in human skin. Specific Aim 1 quantifies the skin sympathetic nerve activity (SSNA) during progressive skin cooling in older vs. young men and women and its relation to VC. Specific Aim 2 addresses the relative contributionsof noradrenergic and nonnoradrenergic mechanisms in reflexVC inyoung and older subjects. Follow-up experiments are described that will determine the potential role of neuropeptide Y in this age-specific VC response. Specific Aim 3 will examine the dose response characteristics of noradrenergicVC to assess the responsiveness of the aged cutaneous vasculature to norepinephrine. Finally, Specific Aim 4 involves a series of whole-body chamber experiments designed to determine and model the effects of altered VC on the resistance to core-to-skin heat transfer, i.e., tissue resistance (insulation) in the fully vasoconstricted state. Resistance to heat loss is a function of both physiological adjustments (VC) and characteristics of the passive system (e.g., muscle mass). Because a common sequelae of human aging is a progressive loss of muscle mass (sarcopenia), sarcopenic elderly men and women may be at even greater risk of hypothermia and hypothermia-related problems. Therefore, the proposed studies under Specific Aim 4 will include differences in muscle mass within age groups.

描述（由申请人提供）：R 01 AG 07004的竞争性更新继续我们对原发性人类衰老皮肤血流（SkappaBF）的温度调节控制改变的机制及其后果的系统研究。 皮肤对高温刺激的血管舒张反应（VD）和对低温刺激的血管收缩反应（VC）均明显减弱。 上一个资助周期涉及对老年男性和女性皮肤VD改变相关机制的系统性研究（简要总结见本提案的C节）。 下一个拟议的研究序列是这一调查路线的逻辑延伸，即，检查老化皮肤中改变的皮肤VC的机制和后果，因为（1）原发性老化与冷应激引起的核心温度的较大降低和临床体温过低的发生率增加两者相关，（2）这些不利后果主要是相对不能收缩皮肤脉管系统导致核心到皮肤的热传递增加的结果，（3）在传出VC控制通路中存在几个可能的年龄相关变化位点，这些位点尚未在体内测试。 此外，由于VC降低和核心-皮肤热阻降低的综合作用，体重和瘦肌肉质量较低的老年男性和女性患低体温症的风险更大。 具体目标1-3分别在交感神经传递、神经递质/受体和终末器官反应水平检查老年皮肤中衰减反射VC的基本传出机制。 这些研究利用新的和最近改进的技术，允许在体内检查与年龄有关的变化，在人类皮肤。 特定目标1量化了老年与年轻男性和女性进行性皮肤冷却期间的皮肤交感神经活动（SSNA）及其与VC的关系。 具体目标2阐述了年轻和老年受试者反射VC中去甲肾上腺素能和非去甲肾上腺素能机制的相对贡献。 后续实验将确定神经肽Y在这个年龄特异性VC反应的潜在作用。 具体目标3将检查去甲肾上腺素能VC的剂量反应特征，以评估老年皮肤血管对去甲肾上腺素的反应性。 最后，具体目标4涉及一系列全身腔室实验，旨在确定和模拟改变的VC对核心到皮肤传热阻力的影响，即，在完全血管收缩状态下的组织电阻（绝缘）。 对热损失的抵抗力是生理调节（VC）和被动系统的特性（例如，肌肉质量）。 由于人类衰老的常见后遗症是肌肉质量的进行性损失（肌肉减少症），肌肉减少症的老年男性和女性可能处于体温过低和低血糖相关问题的更大风险中。 因此，具体目标4下的拟议研究将包括年龄组内肌肉质量的差异。