AGE AND CONTROL OF HUMAN SKIN BLOOD-FLOW

人类皮肤血流的年龄和控制

• 批准号: 6726359
• 负责人: W. LARRY KENNEY
• 金额: $ 34.18万
• 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 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6726359
• 关键词: age difference; baroreceptors; body temperature; body temperature regulation; clinical research; environmental stressor; exercise; gender difference; human old age (65+); human subject; neural transmission; neuropeptide Y; neurotransmitter receptor; psychometrics; skin circulation; sympathetic nervous system; ultrasound blood flow measurement; vasoconstriction; vasodilation; young adult human (21-34)

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）：R01 AG07004的这种竞争性更新继续我们对具有人类衰老及其后果的皮肤血流（Skappabf）的影响改变的机制的系统研究。 对高温刺激和皮肤血管收缩（VC）的响应，两种皮肤血管舒张（VD）响应于衰老的皮肤中的低温刺激作用。 先前的资金周期涉及对年龄较大的男女皮肤VD改变的机制进行系统的研究（在本提案的C节中简要概述）。 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核心对皮肤传热，（3）在未在体内测试的传出VC控制途径中存在几种与年龄相关变化的合理位点。 此外，由于VC降低和核心对皮肤的热耐药性的综合作用，体温下的老年男性和女性的体温过低，体温过低的风险更高。 具体目的1-3分别检查了在交感神经传播，神经递质/受体和最终器官反应水平的老年皮肤中减弱反射VC的基本传出机制。 这些研究利用了新的和最近精致的技术，可以在体内检查与年龄相关的人皮肤变化。 特定的目标1量化了在年龄较大的男女及其与VC的关系中，在进行性皮肤冷却过程中，皮肤交感神经活动（SSNA）量化。 具体目的2解决了反射和较旧受试者中去甲肾上腺素能和非肾上腺素能机制的相对贡献。 描述了随访实验，该实验将确定神经肽Y在该年龄特异性VC反应中的潜在作用。 具体目标3将检查去甲肾上腺素能的剂量反应特征，以评估年龄皮肤脉管系统对去甲肾上腺素的反应性。 最后，特定的目标4涉及一系列全身室实验，旨在确定和模拟VC改变的影响对核心对皮肤传热的耐药性，即完全血管收缩状态下的组织耐药性（绝缘）。 对热量损失的抵抗力是生理调整（VC）和被动系统（例如肌肉质量）的特征的函数。 由于人类衰老的常见后遗症是肌肉质量（肌肉减少症）的逐渐丧失，因此肌肉减少症的老年男性和女性可能会面临低温和与低温相关的问题的更大风险。 因此，在特定目标4下提出的研究将包括年龄组内肌肉质量的差异。