Enhanced Branched-Chain Amino Acid Metabolism Improves Age-Related Reproduction in C. elegans.

IF 4 2区文学 Q1 EDUCATION & EDUCATIONAL RESEARCH

Language Teaching Pub Date : 2024-02-09 DOI:10.1101/2023.02.09.527915

Chen Lesnik, Rachel Kaletsky, Jasmine M Ashraf, Salman Sohrabi, Vanessa Cota, Titas Sengupta, William Keyes, Shijing Luo, Coleen T Murphy

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引用次数: 0

Abstract

Reproductive aging is one of the earliest human aging phenotypes, and mitochondrial dysfunction has been linked to oocyte quality decline. However, it is not known which mitochondrial metabolic processes are critical for oocyte quality maintenance with age. To understand how mitochondrial processes contribute to C. elegans oocyte quality, we characterized the mitochondrial proteomes of young and aged wild-type and long-reproductive daf-2 mutants. Here we show that the mitochondrial proteomic profiles of young wild-type and daf-2 worms are similar and share upregulation of branched-chain amino acid (BCAA) metabolism pathway enzymes. Reduction of the BCAA catabolism enzyme BCAT-1 shortens reproduction, elevates mitochondrial reactive oxygen species levels, and shifts mitochondrial localization. Moreover, bcat-1 knockdown decreases oocyte quality in daf-2 worms and reduces reproductive capability, indicating the role of this pathway in the maintenance of oocyte quality with age. Importantly, oocyte quality deterioration can be delayed, and reproduction can be extended in wild-type animals both by bcat-1 overexpression and by supplementing with Vitamin B1, a cofactor needed for BCAA metabolism.

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增强支链氨基酸代谢可改善秀丽隐杆线虫与年龄相关的生殖能力

生殖衰老是人类最早出现的衰老表型之一，线粒体功能障碍与卵母细胞质量下降有关。然而，目前还不知道哪些线粒体代谢过程对卵母细胞质量的维持至关重要。为了了解线粒体过程是如何影响秀丽隐杆线虫卵母细胞质量的，我们对年轻和衰老的野生型和长生殖期的daf-2突变体的线粒体蛋白质组进行了表征。我们在这里发现，野生型幼虫和 daf-2 突变体的线粒体蛋白质组图谱相似，支链氨基酸（BCAA）代谢途径酶的上调程度相同。BCAA分解酶BCAT-1的减少会缩短繁殖期、提高线粒体活性氧水平并改变线粒体定位。此外，敲除 BCAT-1 会降低 daf-2 蠕虫的卵母细胞质量并降低生殖能力，这表明随着年龄的增长，该途径在维持卵母细胞质量方面发挥作用。重要的是，通过过表达 bcat-1 和补充维生素 B1（BCAA 代谢所需的辅助因子），野生型动物的卵母细胞质量恶化可以被延迟，繁殖能力也可以延长。

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来源期刊

Language Teaching Multiple-

CiteScore

7.10

自引率

2.80%

发文量

期刊介绍： Language Teaching is the essential research resource for language professionals providing a rich and expert overview of research in the field of second-language teaching and learning. It offers critical survey articles of recent research on specific topics, second and foreign languages and countries, and invites original research articles reporting on replication studies and meta-analyses. The journal also includes regional surveys of outstanding doctoral dissertations, topic-based research timelines, theme-based research agendas, recent plenary conference speeches, and research-in-progress reports. A thorough peer-reviewing procedure applies to both the commissioned and the unsolicited articles.