Roles of Lipid Metabolism in Regulation of Longevity

脂质代谢在人类健康和长寿中起着关键作用。脂质代谢失调已经被 与许多与年龄有关的疾病有关。脂肪组织作为脂质代谢的主要部位， 内分泌对无脊椎动物和脊椎动物衰老的影响。脂肪储存的改变也 在许多长寿的动物身上观察到的。然而，人们对脂质代谢是如何影响 再加上寿命控制初步研究表明，脂肪酶和脂质伴侣发挥作用， 对秀丽隐杆线虫脂质代谢和寿命的精细控制。脂肪酶和脂质伴侣 在长寿的动物中是上调的，这是它们长寿所必需的。它们的功能也是关键， 野生型和长寿突变体中的脂肪动员。脂肪酶K04A8.5在脂肪中的组成型表达 储存组织促进脂解以及长寿，这与先前已知的在很大程度上不重叠。 长寿机制这些研究提示了脂质代谢控制的新机制， 衰老 本研究拟通过对血脂代谢的研究，探讨血脂代谢在长寿调节中的作用。 具体目标如下：1）研究脂肪酶过表达延长寿命的机制。（二） 描述脂质伴侣在寿命调节中的作用。3)识别脂质信使， 寿命我们将应用遗传学和生物化学技术来剖析细胞中的信号成分。 调节脂肪酶和脂质伴侣功能，特别是它们介导的寿命。此外，我们将 采用脂质组学方法，目的是鉴定特定的脂质种类和人类代谢物， 衰老的关键调节器这些研究将有助于深入了解脂质代谢影响 衰老过程，并提供新的治疗靶点，以改善老年人的代谢健康。

Lipid metabolism plays a key role in human health and longevity. Dysregulation of lipid metabolism has been implicated in many age-related diseases. As a major site of lipid metabolism, adipose tissue exerts crucial endocrine effects on aging in both invertebrate and vertebrate organisms. Altered fat storage has been also observed in a variety of long-lived animals. However, it remains poorly understood how lipid metabolism is coupled to lifespan control. Preliminary studies have suggested that lipases and lipid chaperones exert exquisite control over lipid metabolism and lifespan in Caenorhabditis elegans. Lipases and lipid chaperones are up-regulated in long-lived animals, and necessary for their longevity. Their functions are also pivotal for fat mobilization in wild type and long-lived mutants. Constitute expression ofthe lipase K04A8.5 in fat storage tissue promotes lipolysis as well as longevity, which is largely non-overlapping with previous known longevity mechanisms. These studies suggest novel mechanisms for lipid metabolism in the control of aging. This proposal seeks to dissect the function of lipid metabolism in the regulation of longevity through the following specific aims: 1) Study the mechanisms by which lipase overexpression extends lifespan. 2) Characterize the roles of lipid chaperones in lifespan regulation. 3) Identify lipid messengers that extend lifespan. We will apply genetic and biochemical techniques to dissect the signaling components in the regulation of lipase and lipid chaperone functions, especially their mediated longevity. Additionally, we will employ lipidomic approaches with the goal of identifying particular lipid species and human metabolites as key regulators of aging. These studies will yield insights to mechanisms by which lipid metabolism affects the aging process, and provide novel therapeutic targets to improve metabolic health in elderly.