Amelioration of aged endothelial dysfunction by NAMPT and caloric restriction

描述（由申请人提供）：候选人。候选人安东尼·多纳托博士是犹他州大学内科的心血管生理学家。Donato博士的研究重点是介导动脉衰老的机制，以及热量限制可以随着衰老保持和恢复血管健康的机制。他的长期目标是指导一个独立的、由外部资助的研究实验室，该实验室可以在基因、细胞、组织和全身（全身）水平上综合研究血管衰老，并被公认为转化血管功能的国际领导者。拟议的K 02奖将为Donato博士提供必要的受保护的职业发展时间，以实现这一目标。职业发展计划。该奖项将支持Donato博士的进一步职业发展，使他能够完成分子遗传学和衰老基础生物学方面的全面课程，同时保持他在老年医学方面的培训。职业发展计划包含几个独立但协调的努力，以提高申请人的专业知识，包括与内皮激活和诱导型转基因小鼠创建相关的新实验技术的培训，教学课程工作，旨在促进更好地理解分子遗传学的应用，为研究人员与先进的学位，并继续参加定期老化和老年系列研讨会和其他血管和衰老生物学会议旨在教育和鼓励多纳托博士和其他研究人员在衰老生物学和老年医学研究领域的合作研究。Research.该研究项目的目的是双重的：首先，确定SIRT-1对衰老内皮激活的调节作用和长期热量限制诱导的血管保护作用;其次，确定遗传增强内皮NAMPT表达/活性是否可以改善年龄相关的内皮功能障碍。这些新的和重要的研究将确定NAMPT是否以及如何影响sirtuins和随后的炎症/氧化应激相关的血管老化。预期结果将提供临床 关于整体内皮功能障碍随着衰老而表达的综合生理机制以及NAMPT是否是潜在的治疗靶点的重要信息。

DESCRIPTION (provided by applicant): Candidate. The candidate, Anthony J. Donato Ph.D., is a cardiovascular physiologist in the Department of Internal Medicine at the University of Utah. Dr. Donato's research focuses on the mechanisms mediating arterial aging and the mechanisms by which caloric restriction can preserve and restore vascular health with aging. His long term goal is to direct an independent, extramurally-funded research laboratory that can integratively study vascular aging at the gene, cellular, tissue and systemic (whole-body) levels and to be recognized as an international leader in translational vascular function. The proposed K02 award will provide Dr. Donato the necessary protected career development time to achieve this goal. Career Development Plan. This award will support the further career development of Dr. Donato, allowing him to complete a well-rounded program in molecular genetics and the basic biology of aging while maintaining his training in Geriatrics. The career development plan contains several separate but coordinated efforts to enhance the expertise of the applicant including training in new experimental techniques related to endothelial activation and inducible transgenic mouse creation, didactic course work designed to facilitate better understanding of the application of molecular genetics for investigators with advanced degrees and continued attendance at regular aging and geriatric seminar series and other vascular and basic biology of aging meetings aimed to educate and encourage collaborative research between Dr. Donato and other investigators in the specialties of biology of aging and geriatric research. Research. The aim of the research project is twofold: first, determine the modulatory influence of SIRT-1 on endothelial activation with aging and the vasoprotection induced by long term caloric restriction; second, to determine if genetically augmenting endothelial NAMPT expression/activity can ameliorate age-related endothelial dysfunction. These novel and important studies will determine if, and how, NAMPT influences sirtuins and subsequent inflammation/oxidative stress- related vascular aging. The expected results will provide clinically important information regarding the integrative physiological mechanisms by which global endothelial dysfunction is expressed with aging and if NAMPT is a potential therapeutic target.