Comprehensive study of W06A7.4 and TMEM144 mediated pathways in aging: insights from Caenorhabditis elegans to human.

IF 2.1 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Genetics and Genomics Pub Date : 2025-09-30 DOI:10.1007/s00438-025-02299-7

Li Fang Wang, Xiaorong Liu, Sisi Li, Rong Li, Ran Li, Fengxia Yan, Xi Jing

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引用次数: 0

Abstract

Aging is a major biological process underlying increased risk of chronic and neurodegenerative diseases, yet its molecular mechanisms remain incompletely defined. Our study systematically investigates the conserved functions and pathways of W06A7.4 in Caenorhabditis elegans and its human homolog TMEM144 in the regulation of aging, combining genetic manipulation in model organisms, analysis of human clinical samples, and functional assays in cell lines. The results demonstrate that W06A7.4 promotes longevity in C. elegans through synergistic effects with dietary restriction, reduction of oxidative damage, modulation of IIS and mTOR signaling, and maintenance of mitochondrial membrane potential. In human samples and cellular models, TMEM144 expression increases with age and in Alzheimer's disease. Our results suggest that TMEM144 may be involved in the regulation of glucose transport and mitochondrial respiration via the downstream protein TIMMDC1. These findings advance our understanding of evolutionarily conserved aging pathways and identify W06A7.4/TMEM144 as promising molecular targets for anti-aging and neurodegenerative disease interventions.

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W06A7.4和TMEM144介导的衰老途径的综合研究：从秀丽隐杆线虫到人类的见解

衰老是慢性和神经退行性疾病风险增加的主要生物学过程，但其分子机制仍未完全确定。本研究结合模式生物遗传操作、人类临床样本分析和细胞系功能分析，系统探讨了秀丽隐杆线虫W06A7.4及其人类同源物TMEM144在衰老调控中的保守功能和途径。结果表明，W06A7.4通过与饮食限制、减少氧化损伤、调节IIS和mTOR信号以及维持线粒体膜电位的协同作用，促进线虫的寿命。在人类样本和细胞模型中，TMEM144的表达随着年龄和阿尔茨海默病的增长而增加。我们的研究结果表明，TMEM144可能通过下游蛋白TIMMDC1参与葡萄糖转运和线粒体呼吸的调节。这些发现促进了我们对进化保守的衰老途径的理解，并确定W06A7.4/TMEM144是抗衰老和神经退行性疾病干预的有希望的分子靶点。

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

Molecular Genetics and Genomics 生物-生化与分子生物学

CiteScore

5.10

自引率

3.20%

发文量

134

审稿时长

1 months

期刊介绍： Molecular Genetics and Genomics (MGG) publishes peer-reviewed articles covering all areas of genetics and genomics. Any approach to the study of genes and genomes is considered, be it experimental, theoretical or synthetic. MGG publishes research on all organisms that is of broad interest to those working in the fields of genetics, genomics, biology, medicine and biotechnology. The journal investigates a broad range of topics, including these from recent issues: mechanisms for extending longevity in a variety of organisms; screening of yeast metal homeostasis genes involved in mitochondrial functions; molecular mapping of cultivar-specific avirulence genes in the rice blast fungus and more.