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Kristine Erlandson，MD。她提议的研究将集中在生长激素轴的干扰作为人类免疫缺陷病毒（HIV）感染的成年人身体功能下降的潜在机制。候选人：Erlandson博士是一名董事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/代谢和传染病学科的研究培训，以便她能够发展调查艾滋病毒感染中衰老并发症所需的技能。培训内容：Erlandson的K23职业发展计划将侧重于：1）发展前瞻性纵向临床研究的设计和实施技能; 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）提高老龄化研究的知识和技能，包括进行身体功能评估，运动测试和肌肉活检;以及4）加强研究领导能力和扩大研究合作。导师/环境：Erlandson博士组建了一个由导师和顾问组成的团队，以弥合有效调查艾滋病毒老化所需的多个研究学科。作为导师，坎贝尔、施瓦茨和布朗博士将提供艾滋病毒研究（坎贝尔）、衰老研究（施瓦茨）、生长激素和内分泌学其他方面的专业知识和职业指导（布朗、施瓦茨），以及纵向临床试验的设计和实施（施瓦茨、坎贝尔、布朗）。睡眠（伯吉斯），激素分泌模式的统计分析（卡尔森）和频繁的激素采样（赖特）的合作者将支持Erlandson博士在拟议的培训和研究活动。此外，艾滋病临床试验组的临床研究基础设施、数据管理和统计支持将提供给Erlandson博士，以实施艾滋病临床试验组申办的临床试验。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储存样本和可靠数据将提供具有类似人口统计学和艾滋病毒风险获得因素的对照组。科罗拉多大学将通过科罗拉多临床和转化科学研究所提供研究支持（由美国国立卫生研究院临床转化科学奖支持），研究生院，公共卫生学院，辅导，领导和教学的众多机会，为1500多名患者提供护理的艾滋病毒诊所，一个强大的多学科门诊高级诊所，和哈特福德老年医学中心研究：与类似的艾滋病毒阴性人群相比，艾滋病毒阳性者，即使在接受有效的抗逆转录病毒治疗时，发病率和死亡率也过高。接受抗逆转录病毒疗法的人很少死于艾滋病并发症，但却有早期的衰老并发症，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与某些衰老队列中的虚弱、肌肉减少症（低肌肉质量和力量）和死亡率相关。在我们接受有效ART的中年HIV+成年人队列中，较低的IGF-I与功能障碍的可能性显着增加相关。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。使用五个独特的现有队列，拟议的项目将评估IGF-I与HIV+和HIV-成人之间144周内功能损害的纵向关联（目标1）;随机开始ART的IGF-I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）。总结：这将是第一项评估1）IGF-I与老年HIV+成人身体功能轨迹的关联，2）ART启动对HIV感染者IGF-I的影响，以及3）有或无HIV感染的老年人24小时GH分泌模式的研究。Erlandson博士实施这项指导性研究和培训建议“艾滋病毒和衰老对身体功能和躯体疾病的影响”，将促进她发展成为艾滋病毒，成功衰老和身体功能领域的独立调查员和领导者。