Oxidative stress-induced gene expression changes in prostate epithelial cells in vitro reveal a robust signature of normal prostatic senescence and aging.

IF 4.4 4区 医学 Q1 GERIATRICS & GERONTOLOGY
Biogerontology Pub Date : 2024-11-01 Epub Date: 2024-08-20 DOI:10.1007/s10522-024-10126-6
Samael Olascoaga, Jorge I Castañeda-Sánchez, Mina Königsberg, Humberto Gutierrez, Norma Edith López-Diazguerrero
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引用次数: 0

Abstract

Oxidative stress has long been postulated to play an essential role in aging mechanisms, and numerous forms of molecular damage associated with oxidative stress have been well documented. However, the extent to which changes in gene expression in direct response to oxidative stress are related to actual cellular aging, senescence, and age-related functional decline remains unclear. Here, we ask whether H2O2-induced oxidative stress and resulting gene expression alterations in prostate epithelial cells in vitro reveal gene regulatory changes typically observed in naturally aging prostate tissue and age-related prostate disease. While a broad range of significant changes observed in the expression of non-coding transcripts implicated in senescence-related responses, we also note an overrepresentation of gene-splicing events among differentially expressed protein-coding genes induced by H2O2. Additionally, the collective expression of these H2O2-induced DEGs is linked to age-related pathological dysfunction, with their protein products exhibiting a dense network of protein-protein interactions. In contrast, co-expression analysis of available gene expression data reveals a naturally occurring highly coordinated expression of H2O2-induced DEGs in normally aging prostate tissue. Furthermore, we find that oxidative stress-induced DEGs statistically overrepresent well-known senescence-related signatures. Our results show that oxidative stress-induced gene expression in prostate epithelial cells in vitro reveals gene regulatory changes typically observed in naturally aging prostate tissue and age-related prostate disease.

Abstract Image

氧化应激诱导的体外前列腺上皮细胞基因表达变化揭示了正常前列腺衰老和老化的强大特征。
长期以来,人们一直认为氧化应激在衰老机制中扮演着重要角色,与氧化应激相关的多种分子损伤形式也已被充分记录。然而,对氧化应激直接反应的基因表达变化在多大程度上与实际的细胞衰老、衰老和与年龄相关的功能衰退有关仍不清楚。在这里,我们提出了一个问题:H2O2 诱导的氧化应激以及由此导致的体外前列腺上皮细胞基因表达改变是否揭示了在自然衰老的前列腺组织和与年龄相关的前列腺疾病中观察到的典型基因调控变化。我们观察到与衰老相关反应有牵连的非编码转录本的表达发生了广泛的显著变化,同时我们还注意到在 H2O2 诱导的不同表达蛋白编码基因中,基因剪接事件的比例过高。此外,这些由 H2O2 诱导的 DEGs 的集体表达与年龄相关的病理功能障碍有关,其蛋白产物表现出密集的蛋白-蛋白相互作用网络。与此相反,对现有基因表达数据的共表达分析表明,在正常衰老的前列腺组织中,H2O2 诱导的 DEGs 自然存在高度协调的表达。此外,我们还发现氧化应激诱导的 DEGs 在统计学上超过了众所周知的衰老相关特征。我们的研究结果表明,氧化应激诱导的体外前列腺上皮细胞基因表达揭示了在自然衰老的前列腺组织和与年龄相关的前列腺疾病中观察到的典型基因调控变化。
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来源期刊
Biogerontology
Biogerontology 医学-老年医学
CiteScore
8.00
自引率
4.40%
发文量
54
审稿时长
>12 weeks
期刊介绍: The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments. Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.
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