The Impact of HIV and Aging on Physical Function and the Somatopause.

艾滋病毒和衰老对身体功能和躯体更年期的影响。

• 批准号: 9064699
• 负责人: Kristine Mace Erlandson
• 金额: $ 17.94万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9064699
• 关键词: 20 year old; AIDS clinical trial group; Acquired Immunodeficiency Syndrome; Adult; Age; Age-Years; Aging; Biopsy; Body Composition; Caring; Cessation of life; Chronic; Clinic; Clinical Research; Clinical Sciences; Clinical Trials; Clinical and Translational Science Awards; Cohort Studies; Collaborations; Colorado; Communicable Diseases; Control Groups; Cross-Sectional Studies; Data; Development; Development Plans; Discipline; Educational process of instructing; Elderly; Endocrinology; Environment; Exercise stress test; Frequencies; Geriatrics; Goals; HIV; HIV Envelope Protein gp120; HIV-1; Health; Heterogeneity; Hormones; Hospitalization; Hour; Hypothalamic structure; Immune; Immunosuppression; Impairment; Infection; Inflammation; Injection of therapeutic agent; Institutes; Insulin-Like Growth Factor I; Internist; K-Series Research Career Programs; Knowledge; Leadership; Learning; Life; Life Style; Lipodystrophy; Measures; Mediator of activation protein; Medical; Medicine; Mentors; Morbidity - disease rate; Muscle; Nucleosides; Nursing Homes; Observational Study; Outpatients; Pathogenesis; Pathway interactions; Patients; Pattern; Persons; Phenotype; Physical Function; Physical Performance; Physiologic pulse; Population; Public Health Schools; Quality of life; Randomized; Regimen; Research; Research Activity; Research Infrastructure; Research Personnel; Research Support; Research Training; Reverse Transcriptase Inhibitors; Risk; Rodent Model; Role; Sampling; Schools; Serum; Sleep; Social isolation; Somatotropin; Specialist; Statistical Data Interpretation; Tenofovir; Training; Training Activity; Translational Research; United States; United States National Institutes of Health; Universities; Virus Diseases; Vocational Guidance; Woman; Zidovudine; aged; antiretroviral therapy; base; bone; career development; co-infection; cohort; data management; design; disability; early onset; env Gene Products; experience; frailty; functional decline; functional disability; growth hormone deficiency; hormone resistance; improved; medical schools; middle age; mortality; muscle strength; patient oriented; professor; prospective; reconstitution; reduced muscle mass; research study; sarcopenia; skills; success; symposium; virus envelope; wasting

DESCRIPTION (provided by applicant): This is a revised application for a K23 Patient-Oriented Mentored Career Development award by Kristine Erlandson, MD. Her proposed research will focus on disturbance in the growth hormone axis as a potential mechanism for physical function decline among human immunodeficiency virus (HIV)-infected adults. Candidate: Dr. Erlandson is a board-certified internist and infectious disease specialist. She is currently an Assistant Professor of Medicine in the Divisions of Infectious Diseases and Geriatric Medicine at the University of Colorado Denver-Anschutz Medical Campus School of Medicine. Dr. Erlandson seeks research training in the disciplines of geriatric medicine, endocrinology/metabolism, and infectious diseases so she can develop the skills needed to investigate complications of aging in HIV infection. Training: Through hands-on mentored research, formal coursework, and conferences/seminars, Dr. Erlandson's K23 career development plan will focus on: 1) developing skills in design and implementation of prospective longitudinal clinical research studies; 2) learning to conduct, analyze and interpret studies of th growth hormone axis, including effects of sleep; 3) improving knowledge & skills for aging research including conduct of physical function assessments, exercise testing, and muscle biopsies; and 4) strengthening research leadership abilities and expanding research collaborations. Mentors/Environment: Dr. Erlandson has assembled a team of mentors and consultants to bridge the multiple research disciplines necessary to effectively investigate aging in HIV. As mentors, Drs. Campbell, Schwartz, and Brown will provide expertise and career guidance in HIV research (Campbell), aging research (Schwartz), growth hormone and other aspects of endocrinology (Brown, Schwartz), design and conduct of longitudinal clinical trials (Schwartz, Campbell, Brown). Collaborators in sleep (Burgess), statistical analysis of hormone secretion patterns (Carlson), and frequent hormone sampling (Wright) will support Dr. Erlandson in the proposed training and research activities. Additionally, clinical research infrastructure, data management, and statistical support of the AIDS Clinical Trials Group will be available to Dr. Erlandson for the implementation of AIDS Clinical Trials Group-sponsored clinical trials. The stored samples and robust data from HIV-uninfected persons from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study will provide a control group with similar demographic and HIV risk acquisition factors. The University of Colorado will provide research support through the Colorado Clinical and Translational Science Institute (supported by the NIH Clinical Translational Sciences Award), the Graduate School, School of Public Health, numerous opportunities for mentoring, leadership, and teaching, an HIV clinic that provides care for over 1500 patients, a robust multi-disciplinary outpatient Senior's Clinic, and the Hartford Center for Geriatric Excellence. Research: In comparison to similar HIV- populations, HIV+ persons, even when on effective antiretroviral therapy, experience an excess of morbidity and mortality. Persons on ART rarely die from complications of AIDS, but instead have early onset of aging complications including impaired physical function5,16,17, frailty18-22, and falls4. Insulin-like growth factor (IGF)-I is the primary mediator of growth hormone (GH) on muscle and bone. Low IGF-I is associated with frailty, sarcopenia (low muscle mass and strength), and mortality in some aging cohorts. In our cohort of middle-aged HIV+ adults on effective ART, lower IGF-I was associated with a significantly greater odds of functional impairment. Based on our data, we believe impairment in the GH/IGF-I axis may be an important pathway leading to aging complications in HIV. Using five unique, existing cohorts, the proposed project will evaluate the longitudinal association of IGF-I with functional impairment over 144 weeks between HIV+ and HIV- adults (Aim 1); the change in IGF-I with randomized initiation of ART (Aim 2); and the impact of both HIV and age on 24-hour GH secretory patterns (Aim 3). Summary: This will be the first study to evaluate 1) an association of IGF-I with the physical function trajectory among older HIV+ adults, 2) the impact of ART initiation on IGF-I among persons with HIV, and 3) the 24-hour GH secretion patterns in older adults with or without HIV infection. Dr. Erlandson's implementation of this mentored research and training proposal "The Impact of HIV and Aging on Physical Function and the Somatopause," will facilitate her development into an independent investigator and leader in the fields of HIV, successful aging, and physical function.

描述（由申请人提供）：这是 K23 以患者为导向的指导职业发展奖的修订申请，由医学博士 Kristine Erlandson 提出。她提出的研究将重点关注生长激素轴的紊乱，这是人类免疫缺陷病毒（HIV）感染的成年人身体功能下降的潜在机制。候选人：Erlandson 博士是一位经过委员会认证的内科医生和传染病专家。她目前是科罗拉多大学丹佛-安舒茨医学院医学院传染病和老年医学系的医学助理教授。 Erlandson 博士寻求老年医学、内分泌学/代谢学和传染病等学科的研究培训，以便培养研究艾滋病毒感染引起的衰老并发症所需的技能。培训：通过实践指导研究、正式课程和会议/研讨会，Erlandson 博士的 K23 职业发展计划将重点关注：1）培养设计和实施前瞻性纵向临床研究的技能； 2) 学习进行、分析和解释生长激素轴的研究，包括睡眠的影响； 3）提高衰老研究的知识和技能，包括进行身体功能评估、运动测试和肌肉活检； 4）加强研究领导能力并扩大研究合作。导师/环境：Erlandson 博士组建了一支导师和顾问团队，以桥接有效研究艾滋病毒衰老所需的多个研究学科。作为导师，博士。坎贝尔、施瓦茨和布朗将在艾滋病毒研究（坎贝尔）、衰老研究（施瓦茨）、生长激素和内分泌学其他方面（布朗、施瓦茨）、纵向临床试验的设计和实施（施瓦茨、坎贝尔、棕色的）。睡眠方面的合作者 (Burgess)、激素分泌模式的统计分析 (Carlson) 和频繁的激素采样 (Wright) 将支持 Erlandson 博士拟议的培训和研究活动。此外，Erlandson 博士还将获得艾滋病临床试验小组的临床研究基础设施、数据管理和统计支持，以实施艾滋病临床试验小组赞助的临床试验。来自多中心艾滋病队列研究和妇女机构间艾滋病毒研究的未感染艾滋病毒者的存储样本和可靠数据将为对照组提供类似的人口统计和艾滋病毒风险获取因素。科罗拉多大学将通过科罗拉多临床和转化科学研究所（由 NIH 临床转化科学奖支持）、研究生院、公共卫生学院、大量指导、领导和教学机会以及艾滋病毒诊所提供研究支持，为超过 1500 名患者提供护理，设有强大的多学科门诊老年诊所和哈特福德老年卓越中心。研究：与类似的艾滋病毒感染者相比，艾滋病毒感染者即使接受有效的抗逆转录病毒治疗，其发病率和死亡率也会较高。接受抗逆转录病毒疗法的人很少死于艾滋病并发症，而是早期出现衰老并发症，包括身体功能受损5,16,17、虚弱18-22和跌倒4。胰岛素样生长因子 (IGF)-I 是生长激素 (GH) 对肌肉和骨骼的主要介质。低 IGF-I 与某些老龄群体的虚弱、肌肉减少症（肌肉质量和力量低）和死亡率有关。在我们接受有效 ART 治疗的中年 HIV+ 成年人队列中，较低的 IGF-I 与功能障碍的几率显着增加相关。根据我们的数据，我们认为 GH/IGF-I 轴的损伤可能是导致 HIV 衰老并发症的重要途径。拟议的项目将利用五个独特的现有队列，评估 HIV+ 和 HIV- 成人之间 144 周内 IGF-I 与功能障碍的纵向关联（目标 1）；随机开始 ART 后 IGF-I 的变化（目标 2）；以及 HIV 和年龄对 24 小时 GH 分泌模式的影响（目标 3）。摘要：这将是第一项评估 1) IGF-I 与老年 HIV+ 成年人身体机能轨迹之间关系的研究，2) 开始 ART 对 HIV 感染者中 IGF-I 的影响，以及 3) 24-感染或未感染 HIV 的老年人每小时 GH 分泌模式。埃尔兰森博士实施了这项指导性研究和培训计划“艾滋病毒和衰老对身体功能和躯体停经的影响”，这将有助于她发展成为艾滋病毒、成功衰老和身体功能领域的独立研究者和领导者。