Roles of Lipid Metabolism in Regulation of Longevity

脂代谢对人类的健康和长寿起着至关重要的作用。脂类代谢失调一直是 与许多与年龄有关的疾病有关。脂肪组织作为脂类代谢的主要部位，发挥着至关重要的作用。 无脊椎动物和脊椎动物的内分泌对衰老的影响。改变后的脂肪储存也被 在各种长寿动物身上观察到的。然而，人们对脂类代谢如何仍知之甚少。 与寿命控制相结合。初步研究表明，脂肪酶和脂质伴侣蛋白对 对秀丽线虫脂代谢和寿命的精细控制。脂肪酶和脂质伴侣 在长寿动物中上调，对它们的长寿是必要的。它们的功能也是 野生型和长寿突变体的脂肪动员。脂肪酶K04A8.5在脂肪中的组成表达 储存组织促进脂肪分解和长寿，这在很大程度上与先前已知的不重叠 长寿机制。这些研究提示脂代谢在控制糖尿病中的新机制 衰老。 这项建议试图剖析脂代谢在调节长寿中的作用，通过 具体目标如下：1)研究脂肪酶过表达延长寿命的机制。2) 描述脂质伴侣在寿命调节中的作用。3)确定延伸的脂质信使 寿命。我们将应用遗传和生化技术来剖析细胞中的信号成分。 调节脂肪酶和脂质伴侣的功能，特别是它们介导的长寿。此外，我们还将 使用脂质组学方法，目标是确定特定的脂质物种和人类代谢物 老龄化的关键调控因素。这些研究将对脂类代谢的影响机制有深入的了解。 为改善老年人的代谢健康提供了新的治疗靶点。

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.