Mid-Career Research and Mentorship in Metabolic Aging

项目概要/摘要 葡萄糖和脂质代谢失调是人类衰老的核心特征，在衰老过程中发挥着重要作用。 老年人中普遍存在的高度病态的心脏代谢疾病，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 (NEFA) 长期以来一直受到牵连 作为新陈代谢受损的核心因素，可能是代谢衰老的许多不利影响的根源， 包括认知能力下降和虚弱。 肯尼思·穆卡马尔 (Kenneth Mukamal) 博士是一名普通内科医生，他进行了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。这个 研究主要集中在心血管健康研究 (CHS)，这是一项由 NHLBI 和 NIA 资助的队列 对来自美国四个社区的 5,888 名 65 岁及以上成年人进行的研究，以及 Ginkgo 记忆力评估 研究 (GEMS)，一项随机试验，对部分中枢性低通气综合症 (CHS) 患者进行了额外的痴呆症随访 参与者。 Mukamal 博士担任 CHS 指导委员会成员并担任糖尿病委员会主席 工作组。 Mukamal 博士正在进行的研究支持 (R01-AG-053325) 资助了总额的测量， 独特的 CHS 队列中的个体和葡萄糖负荷后 NEFA。他最近的工作表明 总 NEFA 与中枢性低通气综合症 (CHS) 患者的认知能力下降和判定的痴呆有关。最近有两个支持 补充剂——用于支持 Mukamal 博士指导的一位代表性不足的少数族裔科学家和一位 第二个支持针对 NOT-AG-18-008 的 ADRD 研究 – Mukamal 博士目前正在积极调查 个体和负荷后 NEFA 在中枢性低通气综合症 (CHS) 和其他地方的痴呆和虚弱中的作用。 Mukamal 博士在指导年轻科学家方面有着长期、一致和杰出的记录，服务于 在各种环境中担任重要的教育角色，并因其杰出的表现而受到正式认可 研究指导。以患者为导向的研究中的职业生涯中期研究员奖将使他能够 通过减少行政职责并提供指导，扩大和深化他对指导的承诺 直接支持专门针对代谢障碍的集中、密集的指导活动 老化。此外，该奖项将使Mukamal博士能够进一步发展自己的职业生涯并获得 对于进一步将其工作扩展到痴呆症领域至关重要的领域的知识、熟悉度和专业知识，例如 随着认知评估和神经影像学的进步。结合优越的环境 在贝斯以色列女执事医疗中心、哈佛医学院和哈佛 TH 接受培训和指导 陈公共卫生学院，该奖项将使 Mukamal 博士能够扩大和改进他的指导 经验，从而有助于培训下一代代谢衰老研究人员。

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.