年龄依赖性核脂滴沉积是秀丽隐杆线虫衰老的细胞标志,Aging Cell

当前位置： X-MOL 学术 › Aging Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

年龄依赖性核脂滴沉积是秀丽隐杆线虫衰老的细胞标志
Aging Cell ( IF 8.0 ) Pub Date : 2023-01-31 , DOI: 10.1111/acel.13788
Konstantinos Palikaras ₁ , Meropi Mari ₂ , Christina Ploumi _{3,

4} , Andrea Princz ₃ , George Filippidis ₂ , Nektarios Tavernarakis _{3,

4}

Affiliation

衰老是多种危及生命的病理的主要危险因素，并且会损害多个细胞区室和细胞器的功能。核形态的年龄依赖性退化是进化不同的生物体的一个共同特征。脂滴已被证明定位于大多数核室，它们会影响基因组结构和完整性。然而，进行性核脂质积累的意义及其对机体稳态的影响仍然不清楚。在这里，我们实施非线性成像模式来监测和量化秀丽隐杆线虫中依赖于年龄的核脂质沉积。我们发现，在衰老过程中，脂滴越来越多地积聚在核膜中。促进长寿的干预措施，例如低胰岛素信号和热量限制，可以消除核脂质累积的速度并减小脂滴的大小。皮下和肠核中脂毒性脂质积累的抑制取决于转录因子 HLH-30/TFEB 和甘油三酯脂肪酶 ATGL-1。HLH-30 调节 ATGL-1 的表达以减少核脂滴丰度以响应延长寿命的条件。值得注意的是，ATGL-1 定位于核膜并在衰老过程中调节长寿突变线虫的脂质含量。我们的研究结果表明，ATGL-1 活性降低会导致核脂质过度积累，扰乱核稳态并破坏机体生理学，

"点击查看英文标题和摘要"

Age-dependent nuclear lipid droplet deposition is a cellular hallmark of aging in Caenorhabditis elegans

Aging is the major risk factor for several life-threatening pathologies and impairs the function of multiple cellular compartments and organelles. Age-dependent deterioration of nuclear morphology is a common feature in evolutionarily divergent organisms. Lipid droplets have been shown to localize in most nuclear compartments, where they impinge on genome architecture and integrity. However, the significance of progressive nuclear lipid accumulation and its impact on organismal homeostasis remain obscure. Here, we implement non-linear imaging modalities to monitor and quantify age-dependent nuclear lipid deposition in Caenorhabditis elegans. We find that lipid droplets increasingly accumulate in the nuclear envelope, during aging. Longevity-promoting interventions, such as low insulin signaling and caloric restriction, abolish the rate of nuclear lipid accrual and decrease the size of lipid droplets. Suppression of lipotoxic lipid accumulation in hypodermal and intestinal nuclei is dependent on the transcription factor HLH-30/TFEB and the triglyceride lipase ATGL-1. HLH-30 regulates the expression of ATGL-1 to reduce nuclear lipid droplet abundance in response to lifespan-extending conditions. Notably, ATGL-1 localizes to the nuclear envelope and moderates lipid content in long-lived mutant nematodes during aging. Our findings indicate that the reduced ATGL-1 activity leads to excessive nuclear lipid accumulation, perturbing nuclear homeostasis and undermining organismal physiology, during aging.

更新日期：2023-01-31

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南