The translation initiation factor eIF2α regulates lipid homeostasis and metabolic aging.

IF 8 1区 医学 Q1 CELL BIOLOGY
Aging Cell Pub Date : 2024-10-15 DOI:10.1111/acel.14348
Haipeng Huang, Yilie Liao, Ning Li, Xingfan Qu, Chaocan Li, Jiaqi Hou
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Abstract

Aging is usually accompanied by excessive body fat gain, leading to increased susceptibility to comorbidities. This study aimed to explore an unexpected function for the eukaryotic initiation factor-2α (eIF2α) during aging. Reducing the eIF2α dose led to a reconfiguration of the metabolic equilibrium, promoting catabolism, facilitating lipolysis, and decreasing body fat accumulation while maintaining healthy glucose and lipid metabolism during aging. Specifically, eIF2α enhanced the expression of distinct messenger RNAs encoding mitochondrial electron transport chain proteins at the translation level. The mitochondrial respiration increased in eIF2α heterozygotes, even during aging. Deceleration of translation was demonstrated as a conserved mechanism for promoting longevity across various species. Our findings demonstrated that the restriction of translation by reducing eIF2α expression could fend off multiple tissue damage and improve metabolic homeostasis during aging. Hence, eIF2α was a crucial target for benefiting mammalian aging achieving delayed mammalian aging.

翻译起始因子 eIF2α 调节脂质平衡和代谢衰老。
衰老通常伴随着身体脂肪的过度增加,从而导致更容易患上合并症。这项研究旨在探索真核生物起始因子-2α(eIF2α)在衰老过程中的一种意想不到的功能。减少 eIF2α 的剂量会导致代谢平衡的重新配置,促进分解代谢,促进脂肪分解,减少体内脂肪积累,同时在衰老过程中保持健康的葡萄糖和脂质代谢。具体来说,eIF2α 在翻译水平上增强了编码线粒体电子传递链蛋白的不同信使 RNA 的表达。即使在衰老过程中,eIF2α杂合子的线粒体呼吸也会增加。翻译减速被证明是促进不同物种长寿的一种保守机制。我们的研究结果表明,通过减少 eIF2α 的表达来限制翻译,可以在衰老过程中抵御多种组织损伤并改善代谢平衡。因此,eIF2α是有益于哺乳动物衰老实现延缓哺乳动物衰老的关键靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Aging Cell
Aging Cell Biochemistry, Genetics and Molecular Biology-Cell Biology
自引率
2.60%
发文量
212
期刊介绍: Aging Cell is an Open Access journal that focuses on the core aspects of the biology of aging, encompassing the entire spectrum of geroscience. The journal's content is dedicated to publishing research that uncovers the mechanisms behind the aging process and explores the connections between aging and various age-related diseases. This journal aims to provide a comprehensive understanding of the biological underpinnings of aging and its implications for human health. The journal is widely recognized and its content is abstracted and indexed by numerous databases and services, which facilitates its accessibility and impact in the scientific community. These include: Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Academic Search Premier (EBSCO Publishing) Biological Science Database (ProQuest) CAS: Chemical Abstracts Service (ACS) Embase (Elsevier) InfoTrac (GALE Cengage) Ingenta Select ISI Alerting Services Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) Natural Science Collection (ProQuest) PubMed Dietary Supplement Subset (NLM) Science Citation Index Expanded (Clarivate Analytics) SciTech Premium Collection (ProQuest) Web of Science (Clarivate Analytics) Being indexed in these databases ensures that the research published in Aging Cell is discoverable by researchers, clinicians, and other professionals interested in the field of aging and its associated health issues. This broad coverage helps to disseminate the journal's findings and contributes to the advancement of knowledge in geroscience.
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