Samael Olascoaga, Jorge I Castañeda-Sánchez, Mina Königsberg, Humberto Gutierrez, Norma Edith López-Diazguerrero
{"title":"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。","authors":"Samael Olascoaga, Jorge I Castañeda-Sánchez, Mina Königsberg, Humberto Gutierrez, Norma Edith López-Diazguerrero","doi":"10.1007/s10522-024-10126-6","DOIUrl":null,"url":null,"abstract":"<p><p>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 H<sub>2</sub>O<sub>2</sub>-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 H<sub>2</sub>O<sub>2</sub>. Additionally, the collective expression of these H<sub>2</sub>O<sub>2</sub>-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 H<sub>2</sub>O<sub>2</sub>-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.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":" ","pages":"1145-1169"},"PeriodicalIF":4.4000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486819/pdf/","citationCount":"0","resultStr":"{\"title\":\"Oxidative stress-induced gene expression changes in prostate epithelial cells in vitro reveal a robust signature of normal prostatic senescence and aging.\",\"authors\":\"Samael Olascoaga, Jorge I Castañeda-Sánchez, Mina Königsberg, Humberto Gutierrez, Norma Edith López-Diazguerrero\",\"doi\":\"10.1007/s10522-024-10126-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 H<sub>2</sub>O<sub>2</sub>-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 H<sub>2</sub>O<sub>2</sub>. Additionally, the collective expression of these H<sub>2</sub>O<sub>2</sub>-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 H<sub>2</sub>O<sub>2</sub>-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.</p>\",\"PeriodicalId\":8909,\"journal\":{\"name\":\"Biogerontology\",\"volume\":\" \",\"pages\":\"1145-1169\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486819/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biogerontology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10522-024-10126-6\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/20 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"GERIATRICS & GERONTOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biogerontology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10522-024-10126-6","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/20 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
Oxidative stress-induced gene expression changes in prostate epithelial cells in vitro reveal a robust signature of normal prostatic senescence and aging.
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.
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.