使用综合生物信息学和机器学习方法鉴定脂肪组织中与衰老相关的生物标志物：发现ELN、MXD1和FGF21为关键基因。

Identifying aging-related biomarkers in adipose tissue using integrative bioinformatics and machine-learning approaches: discovery of ELN, MXD1, and FGF21 as key genes.

作者信息

Xie Xin, Wang Hongyan, Xiao Fugang, Jiang Xiaoyan, Chen Yan, Huang Chenghu, Tang Dongfeng, Wang Yanzhong, Rui Shunli, Cheng Xi, Deng Bo, Yang Gangyi, Deng Wuquan

机构信息

Department of Endocrinology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Department of Endocrinology and Metabolism, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, Chongqing, China.

出版信息

Front Endocrinol (Lausanne). 2025 Sep 1;16:1638343. doi: 10.3389/fendo.2025.1638343. eCollection 2025.

DOI:10.3389/fendo.2025.1638343

PMID:40958908

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12433875/

Abstract

BACKGROUND

Adipose tissue plays a critical role in aging and age-related diseases. However, the specific molecular and cellular alterations associated with aging in adipose tissue remain incompletely understood.

METHODS

Aging-related differentially expressed genes (DEARGs) were identified by intersecting differentially expressed genes (DEGs) in adipose tissue, age-related genes (ARGs), and human genes linked to aging. Functional enrichment analysis was conducted to explore the potential roles of these DEARGs. Protein-protein interaction (PPI) networks were analyzed using STRING, and hub DEARGs were identified via least absolute shrinkage and selection operator (LASSO) analysis. Oil Red O staining was used to confirm adi-pocyte differentiation, and D-galactose treatment induced cellular senescence. Validation of hub DEARG expression was conducted in an independent dataset and confirmed using quantitative polymerase chain reaction (qPCR) both and .

RESULTS

Forty-nine DEARGs were identified, with functional enrichment analyses revealing significant roles in glucose homeostasis and key aging pathways, including the FoxO and JAK-STAT signaling pathways, Th17 cell dif-ferentiation, growth hormone signaling, the adiponectin pathway, and AMPK pathway. Five hub genes (PCK1, ELN, MXD1, STAT3, and FGF21) were selected through interaction network anal-ysis and LASSO regression. Expression levels of three DEARGs (ELN, MXD1, and FGF21) were validated by qPCR and an independent dataset.

CONCLUSIONS

This study identified three DEARGs (ELN, MXD1, and FGF21) as potential biomarkers of adipose tissue aging, suggesting their role in organismal aging and age-related disease pathways.

摘要

背景

脂肪组织在衰老及与年龄相关的疾病中起关键作用。然而，与脂肪组织衰老相关的具体分子和细胞改变仍未完全明确。

方法

通过将脂肪组织中的差异表达基因（DEGs）、年龄相关基因（ARGs）以及与衰老相关的人类基因进行交叉分析，确定与衰老相关的差异表达基因（DEARGs）。进行功能富集分析以探索这些DEARGs的潜在作用。使用STRING分析蛋白质-蛋白质相互作用（PPI）网络，并通过最小绝对收缩和选择算子（LASSO）分析确定枢纽DEARGs。采用油红O染色确认脂肪细胞分化，D-半乳糖处理诱导细胞衰老。在独立数据集中对枢纽DEARG表达进行验证，并分别使用定量聚合酶链反应（qPCR）进行确认。

结果

共鉴定出49个DEARGs，功能富集分析显示其在葡萄糖稳态及关键衰老途径中起重要作用，包括FoxO和JAK-STAT信号通路、Th17细胞分化、生长激素信号传导、脂联素途径和AMPK途径。通过相互作用网络分析和LASSO回归选择了5个枢纽基因（PCK1、ELN、MXD1、STAT3和FGF21）。通过qPCR和独立数据集验证了3个DEARGs（ELN、MXD1和FGF21）的表达水平。