Aging, Western Diet and Physiological Dysfunction: Exercise and Inflammation

描述（由申请人提供）：候选人Lisa a . Lesniewski博士，科罗拉多大学博尔德分校综合生理学系的生理学家。Lesniewski博士的研究重点是衰老过程中血管和代谢功能障碍的调节机制，以及习惯性有氧运动如何在衰老过程中保持生理功能。她的近期目标是获得新的研究和专业技能，这将帮助她实现她的长期职业目标，即在血管和代谢衰老的预防和治疗方面建立一个成功的独立的、校外资助的研究项目。拟议的KO1奖将为Lesniewski博士实现这一目标提供必要的支持。职业发展计划。Lesniewski博士的研究职业发展培训活动将包括：1)获得与拟议研究计划相关和补充的新研究技能；2)有组织的活动，包括正式的课程作业，参加每周的期刊俱乐部，大学系列研讨会和科学会议，以及与她的指导团队的定期互动。环境。Lesniewski博士的培训环境应该是优秀的。赞助人Douglas Seals博士是一位知名的校外资助科学家，在生物医学衰老研究方面有着成功的指导记录。他由一组由国际公认的调查人员组成的咨询导师补充，每个人都在Lesniewski博士的研究项目和整体培训计划的关键领域提供特定的专业知识。研究。该研究项目的目的是通过加剧慢性低度炎症来确定衰老是否会增加对高脂肪或西方饮食（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预防WD对血管和代谢功能的有害影响。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）方法来确定WD引起炎症相关的内皮和代谢功能障碍的细胞和分子机制，并与衰老和定期运动发挥保护作用。研究结果应提供以下方面的重要临床信息：1)衰老在改变对常见因素WD易感性方面的影响；2)WD引起和习惯性运动预防这些有害影响的机制。

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.