Interdisciplinary Research Program of Bioinformatics and Longevity Science, Pusan National University.
Department of Pharmacy, College of Pharmacy, Pusan National University.
Biol Pharm Bull. 2023;46(4):552-562. doi: 10.1248/bpb.b22-00601.
Aging leads to the functional decline of an organism, which is associated with age and sex. To understand the functional change of kidneys depending on age and sex, we carried out a transcriptome analysis using RNA sequencing (RNA-Seq) data from rat kidneys. Four differentially expressed gene (DEG) sets were generated according to age and sex, and Gene Ontology analysis and overlapping analysis of Kyoto Encyclopedia of Genes and Genomes pathways were performed for the DEG sets. Through the analysis, we revealed that inflammation- and extracellular matrix (ECM)-related genes and pathways were upregulated in both males and females during aging, which was more prominent in old males than in old females. Furthermore, quantitative real-time PCR analysis confirmed that the expression of tumor necrosis factor (TNF) signaling-related genes, Birc3, Socs3, and Tnfrsf1b, and ECM-related genes, Cd44, Col3a1, and Col5a2, which showed that the genes were markedly upregulated in males and not females during aging. Also, hematoxylin-eosin (H&E) staining for histological analysis showed that renal damage was highly shown in old males rather than old females. In conclusion, in the rat kidney, the genes involved in TNF signaling and ECM accumulation are upregulated in males more than in females during aging. These results suggest that the upregulation of the genes may have a higher contribution to age-related kidney inflammation and fibrosis in males than in females.
衰老是导致生物体功能下降的原因，这种功能下降与年龄和性别有关。为了了解肾脏随年龄和性别而发生的功能变化，我们利用来自大鼠肾脏的 RNA 测序 (RNA-Seq) 数据进行了转录组分析。根据年龄和性别生成了四个差异表达基因 (DEG) 集，并对 DEG 集进行了基因本体论分析和京都基因与基因组百科全书通路的重叠分析。通过分析，我们揭示了在衰老过程中，雄性和雌性大鼠的炎症和细胞外基质 (ECM) 相关基因和途径均上调，且老年雄性大鼠比老年雌性大鼠更为明显。此外，实时定量 PCR 分析证实，肿瘤坏死因子 (TNF) 信号相关基因 Birc3、 Socs3 和 Tnfrsf1b 以及 ECM 相关基因 Cd44、Col3a1 和 Col5a2 的表达在衰老过程中雄性显著上调，而雌性则没有。此外，用于组织学分析的苏木精-伊红 (H&E) 染色显示，老年雄性大鼠的肾脏损伤明显高于老年雌性大鼠。总之，在大鼠肾脏中，TNF 信号和 ECM 积累相关基因在衰老过程中雄性的上调程度高于雌性。这些结果表明，这些基因的上调可能对雄性与年龄相关的肾脏炎症和纤维化的贡献高于雌性。
