Comprehensive analysis of aging-related gene expression patterns and identification of potential intervention targets.

IF 3.6 4区 医学 Q1 MEDICINE, GENERAL & INTERNAL Postgraduate Medical Journal Pub Date : 2024-10-03 DOI:10.1093/postmj/qgae131
Sha Yang, Jianning Song, Min Deng, Si Cheng
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Abstract

Purpose: This study aims to understand the molecular mechanisms underlying the aging process and identify potential interventions to mitigate age-related decline and diseases.

Methods: This study utilized the GSE168753 dataset to conduct comprehensive differential gene expression analysis and co-expression module analysis. Machine learning and Mendelian randomization analyses were employed to identify core aging-associated genes and potential drug targets. Molecular docking simulations and mediation analysis were also performed to explore potential compounds and mediators involved in the aging process.

Results: The analysis identified 4164 differentially expressed genes, with 1893 upregulated and 2271 downregulated genes. Co-expression analysis revealed 21 modules, including both positively and negatively correlated modules between older age and younger age groups. Further exploration identified 509 aging-related genes with distinct biological functions. Machine learning and Mendelian randomization analyses identified eight core genes associated with aging, including DPP9, GNAZ, and RELL2. Molecular docking simulations suggested resveratrol, folic acid, and ethinyl estradiol as potential compounds capable of attenuating aging through modulation of RELL2 expression. Mediation analysis indicated that eosinophil counts and neutrophil count might act as mediators in the causal relationship between genes and aging-related indicators.

Conclusion: This comprehensive study provides valuable insights into the molecular mechanisms of aging and offers important implications for the development of anti-aging therapeutics. Key Messages What is already known on this topic - Prior research outlines aging's complexity, necessitating precise molecular targets for intervention. What this study adds - This study identifies novel aging-related genes, potential drug targets, and therapeutic compounds, advancing our understanding of aging mechanisms. How this study might affect research, practice, or policy - Findings may inform targeted therapies for age-related conditions, influencing future research and clinical practices.

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全面分析与衰老相关的基因表达模式,确定潜在的干预目标。
目的:本研究旨在了解衰老过程的分子机制,并确定潜在的干预措施,以缓解与衰老相关的衰退和疾病:本研究利用 GSE168753 数据集进行了全面的差异基因表达分析和共表达模块分析。方法:本研究利用 GSE168753 数据集进行了全面的差异基因表达分析和共表达模块分析,并采用机器学习和孟德尔随机分析来确定与衰老相关的核心基因和潜在的药物靶点。此外,还进行了分子对接模拟和中介分析,以探索参与衰老过程的潜在化合物和介质:结果:分析发现了 4164 个差异表达基因,其中上调基因 1893 个,下调基因 2271 个。共表达分析发现了 21 个模块,包括老年组和年轻组之间的正相关和负相关模块。进一步探索发现了 509 个具有不同生物学功能的衰老相关基因。机器学习和孟德尔随机分析确定了与衰老相关的 8 个核心基因,包括 DPP9、GNAZ 和 RELL2。分子对接模拟表明,白藜芦醇、叶酸和炔雌醇是能够通过调节 RELL2 的表达来延缓衰老的潜在化合物。中介分析表明,嗜酸性粒细胞计数和中性粒细胞计数可能是基因与衰老相关指标之间因果关系的中介:这项综合研究为了解衰老的分子机制提供了有价值的见解,对开发抗衰老疗法具有重要意义。关键信息 有关该主题的已知信息 - 先前的研究概述了衰老的复杂性,因此需要精确的分子靶点进行干预。本研究的新增内容 - 本研究确定了新的衰老相关基因、潜在药物靶点和治疗化合物,促进了我们对衰老机制的了解。本研究可能对研究、实践或政策产生的影响 - 研究结果可能为老年相关疾病的靶向治疗提供依据,从而影响未来的研究和临床实践。
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来源期刊
Postgraduate Medical Journal
Postgraduate Medical Journal 医学-医学:内科
CiteScore
8.50
自引率
2.00%
发文量
131
审稿时长
2.5 months
期刊介绍: Postgraduate Medical Journal is a peer reviewed journal published on behalf of the Fellowship of Postgraduate Medicine. The journal aims to support junior doctors and their teachers and contribute to the continuing professional development of all doctors by publishing papers on a wide range of topics relevant to the practicing clinician and teacher. Papers published in PMJ include those that focus on core competencies; that describe current practice and new developments in all branches of medicine; that describe relevance and impact of translational research on clinical practice; that provide background relevant to examinations; and papers on medical education and medical education research. PMJ supports CPD by providing the opportunity for doctors to publish many types of articles including original clinical research; reviews; quality improvement reports; editorials, and correspondence on clinical matters.
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