Mid-Career Research and Mentorship in Metabolic Aging

项目摘要/摘要 糖脂代谢失调是人类衰老的主要特征，在 高度病态的心脏代谢疾病在老年人中很普遍，包括心血管疾病， 糖尿病和充血性心力衰竭。非酯化或游离脂肪酸(NEFAs)长期以来一直被认为是 作为新陈代谢受损的中心参与者，可能是新陈代谢老化的许多不利影响的基础， 包括认知能力下降和虚弱。 肯尼斯·穆卡马尔博士是一名普通内科医生，他进行了基础广泛的流行病学研究， 特别关注老年人心血管和认知结果的代谢决定因素。这 研究主要集中在心血管健康研究(CHS)上，这是一个由NHLBI和NIA资助的队列 对来自美国四个社区的5888名65岁及以上的成年人进行的研究，以及银杏记忆评估 研究(GEMS)，一项在CHS子集中进行额外痴呆症随访的随机试验 参与者。Mukamal博士是CHS指导委员会的成员，并担任其糖尿病主席 工作组。Mukamal博士正在进行的研究支持(R01-AG-053325)资助了总数的测量， 在独特的CHS队列中，个体和葡萄糖负荷后的NEFA。他最近的工作证明了 在CHS中，总的NEFA与认知能力下降和被判定为痴呆有关。由两个最近的 补充剂-一种支持穆卡马尔博士指导的少数族裔科学家和 第二，支持ADRD研究以回应NOT-AG-18-008-Mukamal博士现在正在积极调查 个体和负荷后的NEFA在社区卫生服务中心和其他地方的痴呆和脆弱中的作用。 穆卡马尔博士在指导年轻科学家方面有着长期、始终如一和卓越的记录，在 在各种环境中担任主要教育角色，并因其杰出的表现而获得正式认可 研究指导。以患者为中心的研究中的职业生涯中期研究员奖将使他能够 通过减少他的管理责任和提供 直接支持集中、密集的指导活动，特别是与代谢障碍有关的活动 衰老。此外，这一奖项将使穆卡马尔博士能够进一步发展自己的事业并获得 对他的工作进一步扩展到痴呆症至关重要的领域的知识、熟悉度和专业知识，如 随着认知评估和神经成像的进步。与卓越的环境相结合 在贝丝以色列女执事医学中心、哈佛医学院和哈佛大学 这一奖项将使Mukamal博士能够扩大和改进他的指导 经验，因此，有助于培训新陈代谢老化方面的下一代研究人员。

Project Summary/Abstract Dysregulation of glucose and lipid metabolism are central features of human aging and play major roles in the highly morbid cardiometabolic conditions prevalent among older adults, including cardiovascular disease, diabetes, and congestive heart failure. Non-esterified, or free, fatty acids (NEFAs) have long been implicated as central actors in impaired metabolism and may underlie many of the adverse effects of metabolic aging, including cognitive decline and frailty. Dr. Kenneth Mukamal, a general internist, has undertaken broad-based epidemiological research with a particular focus on metabolic determinants of cardiovascular and cognitive outcomes among older adults. This research has largely centered on the Cardiovascular Health Study (CHS), an NHLBI- and NIA-funded cohort study of 5,888 adults aged 65 and older from four U.S. communities, and the Ginkgo Evaluation of Memory Study (GEMS), a randomized trial that conducted additional dementia follow-up in a subset of CHS participants. Dr. Mukamal serves as a member of the CHS Steering Committee and chairs its Diabetes Working Group. Dr. Mukamal’s ongoing research support (R01-AG-053325) funds measurement of total, individual and post-glucose-load NEFAs in the unique CHS cohort. His recent work has demonstrated that total NEFAs are associated with cognitive decline and adjudicated dementia in CHS. Supported by two recent supplements – one to support an underrepresented minority scientist whom Dr. Mukamal mentors and a second to support ADRD research in response to NOT-AG-18-008 – Dr. Mukamal is now actively investigating the role of individual and post-load NEFAs in dementia and frailty in CHS and elsewhere. Dr. Mukamal has a long, consistent, and distinguished track record of mentoring young scientists, serving in major educational roles across a variety of settings and having received formal recognition for his outstanding research mentorship. A Midcareer Investigator Award in Patient-Oriented Research would enable him to expand and deepen his commitment to mentoring by reducing his administrative responsibilities and providing direct support for focused, intensive mentoring activities that specifically relate to metabolic impairment in aging. In addition, this award would enable Dr. Mukamal to further develop his own career and gain knowledge, familiarity, and expertise in domains crucial to the further extension of his work into dementia, such as advances in cognitive assessment and neuroimaging. In conjunction with the outstanding environments for training and mentoring at Beth Israel Deaconess Medical Center, Harvard Medical School, and the Harvard TH Chan School of Public Health, this award will enable Dr. Mukamal to expand and improve his mentoring experience and, as a result, help to train the next generation of investigators in metabolic aging.