Ether lipid biosynthesis promotes lifespan extension and enables diverse prolongevity paradigms in Caenorhabditis elegans

Biguanides, including the world’s most prescribed drug for type 2 diabetes, metformin, not only lower blood sugar but also promote longevity in preclinical models. Epidemiologic studies in humans parallel these findings, indicating favorable effects of metformin on longevity and on reducing the incidence and morbidity associated with aging-related diseases. Despite this promise, the full spectrum of molecular effectors responsible for these health benefits remains elusive. Through unbiased screening in C. elegans, we uncovered a role for genes necessary for ether lipid biosynthesis in the favorable effects of biguanides. We demonstrate that biguanides prompt lifespan extension by stimulating ether lipid biogenesis. Loss of the ether lipid biosynthetic machinery also mitigates lifespan extension attributable to dietary restriction, target of rapamycin (TOR) inhibition, and mitochondrial electron transport chain inhibition. A possible mechanistic explanation for this finding is that ether..., Supplementary file 2 for Cedillo, L., Ahsan, F.M., et al., Ether Lipid Biosynthesis Promotes Lifespan Extension and Enables Diverse Prolongevity Paradigms in Caenorhabditis elegans.
This file contains a dataset from the above manuscript in Microsoft Excel format where C. elegans nematodes (wild type and 3 mutants: fard-1, ads-1, and acl-7) were treated with vehicle or phenformin. Data on 3 biological replicates are included. The file has 3 tabs: 1) Raw mass counts for each identified ether lipid  2) Normalized mass counts for each identified ether lipid 3) Normalized and log10 transformed mass counts for each identified ether lipid The means by which data were normalized are described in the associated methods. , This file can be opened in Microsoft Excel (all versions). ,

双胍类（Biguanides）药物涵盖全球处方量最高的2型糖尿病治疗药物二甲双胍（metformin），不仅可降低血糖水平，还能在临床前模型中促进寿命延长。人群流行病学研究与上述发现相契合，提示二甲双胍对寿命具有积极影响，并可降低衰老相关疾病的发病率与病死率。尽管具备此类健康获益潜力，介导其完整分子效应因子谱仍未明确。本研究通过对秀丽隐杆线虫（C. elegans）开展无偏筛选，发现醚脂（ether lipid）生物合成必需基因在双胍类药物的有益效应中发挥关键作用。我们证实，双胍类药物可通过刺激醚脂生物合成实现寿命延长。醚脂生物合成通路的缺失同样会削弱饮食限制、雷帕霉素靶蛋白（TOR）抑制以及线粒体电子传递链抑制所带来的寿命延长效应。针对该发现的潜在机制解释为……，相关内容详见Cedillo L.、Ahsan F.M.等人发表的研究论文《醚脂生物合成促进秀丽隐杆线虫寿命延长并支持多种延寿范式》的补充材料2。

本数据集文件为上述论文的补充材料2，采用Microsoft Excel格式存储。实验对象为秀丽隐杆线虫（野生型及3种突变体：fard-1、ads-1与acl-7），分别经溶剂对照或苯乙双胍（phenformin）处理。数据集包含3次生物学重复的数据。该Excel文件包含3个工作表：1）各鉴定出的醚脂的原始质量计数；2）各鉴定出的醚脂的标准化质量计数；3）各鉴定出的醚脂经标准化并log10转换后的质量计数。数据标准化的具体方式详见关联的方法学部分。本文件可在所有版本的Microsoft Excel软件中打开。