Abstract
BackgroundAging is affected by genetic and environmental factors, and cigarette smoking is strongly associated with accumulation of senescent cells. In this study, we wanted to identify genes that may potentially be beneficial for cell survival in response to cigarette smoke and thereby may contribute to development of cellular senescence.ResultsPrimary human bronchial epithelial cells from five healthy donors were cultured, treated with or without 1.5% cigarette smoke extract (CSE) for 24 h or were passaged into replicative senescence. Transcriptome changes were monitored using RNA-seq in CSE and non-CSE exposed cells and those passaged into replicative senescence. We found that, among 1534 genes differentially regulated during senescence and 599 after CSE exposure, 243 were altered in both conditions, representing strong enrichment. Pathways and gene sets overrepresented in both conditions belonged to cellular processes that regulate reactive oxygen species, proteasome degradation, and NF-κB signaling.ConclusionsOur results offer insights into gene expression responses during cellular aging and cigarette smoke exposure, and identify potential molecular pathways that are altered by cigarette smoke and may also promote airway epithelial cell senescence.
Highlights
Aging is affected by genetic and environmental factors, and cigarette smoking is strongly associated with accumulation of senescent cells
Identification of expression changes upon replicative senescence or cigarette smoke extract (CSE) exposure in Primary human bronchial epithelial cell (pHBEC) To investigate potential shared mechanisms connecting the effects of CSE and cellular senescence, we examined transcripts by RNA-seq from pHBECs cultured from five nonsmokers, as they were passaged into replicative senescence or when treated with CSE at an early passage (Fig. 1a; Additional file 1: Table S1)
Transcripts were measured after 24 h treatment in 1.5% CSE (n = 5), in equivalent unexposed cells, and in cells that had stopped cell proliferation for 2 weeks after nine to eleven passages (Senescence; n = 5)
Summary
Aging is affected by genetic and environmental factors, and cigarette smoking is strongly associated with accumulation of senescent cells. Increase in the number of senescent cells, which are metabolically active but unable to divide, may play a causative role in the development of tissue and organ. Normal human lung fibroblasts and pHBECs irreversibly lose proliferative capacity after roughly 50 and 10 population doublings, respectively [9, 10]. This process, referred to as replicative senescence, appears to be caused by attrition of telomeres, as telomerase activation increases the length of telomeres and life-span in normal human cells
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call