Aging, Western Diet and Physiological Dysfunction: Exercise and Inflammation

描述(由申请人提供)：候选人丽莎·A·莱斯涅夫斯基博士是科罗拉多大学博尔德分校综合生理学系的生理学家。莱斯涅夫斯基博士的研究重点是随着年龄的增长调节血管和代谢功能障碍的机制，以及习惯性有氧运动如何在年龄增长的情况下保持生理功能。她的眼前目标是获得新的研究和专业技能，帮助她实现长期的职业目标，即开发一个成功的独立的、由外部资金资助的预防和治疗血管和代谢衰老的研究计划。拟议的KO1奖项将为莱斯涅夫斯基博士实现这一目标提供必要的支持。职业发展计划。莱斯涅夫斯基博士的研究职业发展培训活动将包括：1)获得与拟议的研究计划相关和补充的新的研究技能；2)有组织的活动，包括正式的课程工作、每周期刊俱乐部、大学系列研讨会和科学会议的出席和报告，以及与她的指导团队的定期互动。环境。莱斯涅夫斯基博士的培训环境应该很好。发起人道格拉斯·西尔斯博士是一位知名的外部资助科学家，在生物医学衰老研究方面有着成功的指导记录。与他相辅相成的是一组咨询导师，他们由国际公认的研究人员组成，每个人都在莱斯涅夫斯基博士的研究项目和整体培训计划的一个关键领域提供具体的专业知识。研究。该研究项目的目的是确定衰老是否通过加剧慢性低度炎症而增加对高脂肪或西式饮食(WD)有害影响的易感性，并确定习惯性运动是否可以通过减少炎症来防止WD对血管和代谢功能的有害影响。这项拟议的研究将在年轻、中年和老年小鼠中使用“整合”(系统到基因)方法，以确定WD导致炎症相关的内皮和代谢功能障碍与衰老和定期运动发挥保护作用的细胞和分子机制。这些结果应该提供临床上重要的信息：1)衰老对改变对常见因素WD易感性的影响；2)WD引起WD的机制和习惯性运动阻止这些有害影响的机制。 公共卫生相关性：WD的高龄和消费与血管和代谢功能障碍及疾病相关。然而，目前尚不清楚WD的不利影响是否会随着年龄的增长而变得更大，发生这种情况的机制，以及这些影响是否可以通过习惯性有氧运动来预防。

DESCRIPTION (provided by applicant): The candidate, Lisa A. Lesniewski Ph.D., is a physiologist in the Department of Integrative Physiology at the University of Colorado at Boulder. Dr. Lesniewski's research focuses on the mechanisms mediating vascular and metabolic dysfunction with aging and how habitual aerobic exercise can preserve physiological function with aging. Her immediate goal is to acquire new research and professional skills that will help her to achieve her long-term career goal of developing a successful independent, extramurally-funded research program on the prevention and treatment of vascular and metabolic aging. The proposed KO1 award will provide Dr. Lesniewski the necessary support to achieve this goal. CAREER DEVELOPMENT PLAN. Dr. Lesniewski's research career development training activities will consist of: 1) acquiring new research skills associated with and complementary to the proposed research plan; and 2) structured activities including formal course-work, attendance and presentations at weekly journal clubs, university seminar series and scientific meetings, and regular interactions with her mentoring team. ENVIRONMENT. The environment for Dr. Lesniewski's training should be outstanding. The sponsor, Dr. Douglas Seals, is a well-established extramurally-funded scientist with a strong record of successful mentoring in biomedical aging research. He is complemented by a group of consulting mentors that consist of internationally- recognized investigators, each providing specific expertise in a key area of Dr. Lesniewski's research project and overall training plan. RESEARCH. The aims of the research project are to establish if aging increases susceptibility to the deleterious effects of a high fat, or Western diet (WD) by exacerbating chronic low grade inflammation and to determine if habitual exercise can prevent the deleterious effects of WD on vascular and metabolic function by reducing inflammation. The proposed research will use an "integrative" (system to gene) approach in young, middle-aged, and older mice to identify the cellular and molecular mechanisms by which WD causes inflammation-associated endothelial and metabolic dysfunction with aging and regular exercise exerts protective effects. The results should provide clinically important information regarding: 1) the influence of aging in altering vulnerability to a commonly encountered factor, WD and 2) the mechanisms by which WD causes and habitual exercise prevents these deleterious effects. PUBLIC HEALTH RELEVANCE: Advancing age and consumption of a WD are associated with vascular and metabolic dysfunction and disease. However, it is unknown if the adverse effects of WD become greater with aging, the mechanisms by which this occurs, and if these effects can be prevented by habitual aerobic exercise.