The effect of pro-inflammatory conditioning and/or high glucose on telomere shortening of aging fibroblasts.
UNLABELLED:Cardiovascular disease and diabetes have been linked to shorter telomeres, but it is not yet clear which risk factors contribute to shorter telomeres in patients. Our aim was to examine whether pro-inflammatory conditioning, in combination or not with high glucose, result in a higher rate...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3781104?pdf=render |
| _version_ | 1811276215054499840 |
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| author | Klelia D Salpea Cecilia G Maubaret Annegret Kathagen Gie Ken-Dror Derek W Gilroy Steve E Humphries |
| author_facet | Klelia D Salpea Cecilia G Maubaret Annegret Kathagen Gie Ken-Dror Derek W Gilroy Steve E Humphries |
| author_sort | Klelia D Salpea |
| collection | DOAJ |
| description | UNLABELLED:Cardiovascular disease and diabetes have been linked to shorter telomeres, but it is not yet clear which risk factors contribute to shorter telomeres in patients. Our aim was to examine whether pro-inflammatory conditioning, in combination or not with high glucose, result in a higher rate of telomere shortening during in vitro cellular ageing. Human fibroblasts from four donors were cultured for 90 days in: 1) medium lacking ascorbic acid only, 2) 10 mM buthionine sulphoximine (BSO) (pro-oxidant), 3) 25 mM D-glucose, 4) 1 ng/ml IL1B and 5) 25 mM D-glucose+1 ng/ml IL1B. Telomere length was measured with qPCR and intracellular reactive oxygen species (ROS) content and cell death with flow cytometry. Cultures treated with high glucose and BSO displayed a significantly lower growth rate, and cultures treated with IL1B showed a trend towards a higher growth rate, compared to the control [Glucose:0.14 PD/day, p<0.001, BSO: 0.11 PD/day, p = 0.006 and IL1B: 0.19 PD/day, p = 0.093 vs. CONTROL:0.16 PD/day]. Telomere shortening with time was significantly accelerated in cultures treated with IL1B compared to the control [IL1B:-0.8%/day (95%CI:-1.1, -0.5) vs. CONTROL:-0.6%/day (95%CI:-0.8, -0.3), p = 0.012]. The hastening of telomere shortening by IL1B was only in part attenuated after adjustment for the number of cell divisions [IL1B:-4.1%/PD (95%CI:-5.7, -2.4) vs. CONTROL:-2.5%/PD (95%CI:-4.4, -0.7), p = 0.067]. The intracellular ROS content displayed 69% increase (p = 0.033) in BSO compared to the control. In aging fibroblasts, pro-inflammatory conditioning aggravates the shortening of telomeres, an effect which was only in part driven by increased cell turnover. High glucose alone did not result in greater production of ROS or telomere shortening. |
| first_indexed | 2024-04-12T23:52:29Z |
| format | Article |
| id | doaj.art-55672c7781604960a6f763eae301e5c7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T23:52:29Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-55672c7781604960a6f763eae301e5c72022-12-22T03:11:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7375610.1371/journal.pone.0073756The effect of pro-inflammatory conditioning and/or high glucose on telomere shortening of aging fibroblasts.Klelia D SalpeaCecilia G MaubaretAnnegret KathagenGie Ken-DrorDerek W GilroySteve E HumphriesUNLABELLED:Cardiovascular disease and diabetes have been linked to shorter telomeres, but it is not yet clear which risk factors contribute to shorter telomeres in patients. Our aim was to examine whether pro-inflammatory conditioning, in combination or not with high glucose, result in a higher rate of telomere shortening during in vitro cellular ageing. Human fibroblasts from four donors were cultured for 90 days in: 1) medium lacking ascorbic acid only, 2) 10 mM buthionine sulphoximine (BSO) (pro-oxidant), 3) 25 mM D-glucose, 4) 1 ng/ml IL1B and 5) 25 mM D-glucose+1 ng/ml IL1B. Telomere length was measured with qPCR and intracellular reactive oxygen species (ROS) content and cell death with flow cytometry. Cultures treated with high glucose and BSO displayed a significantly lower growth rate, and cultures treated with IL1B showed a trend towards a higher growth rate, compared to the control [Glucose:0.14 PD/day, p<0.001, BSO: 0.11 PD/day, p = 0.006 and IL1B: 0.19 PD/day, p = 0.093 vs. CONTROL:0.16 PD/day]. Telomere shortening with time was significantly accelerated in cultures treated with IL1B compared to the control [IL1B:-0.8%/day (95%CI:-1.1, -0.5) vs. CONTROL:-0.6%/day (95%CI:-0.8, -0.3), p = 0.012]. The hastening of telomere shortening by IL1B was only in part attenuated after adjustment for the number of cell divisions [IL1B:-4.1%/PD (95%CI:-5.7, -2.4) vs. CONTROL:-2.5%/PD (95%CI:-4.4, -0.7), p = 0.067]. The intracellular ROS content displayed 69% increase (p = 0.033) in BSO compared to the control. In aging fibroblasts, pro-inflammatory conditioning aggravates the shortening of telomeres, an effect which was only in part driven by increased cell turnover. High glucose alone did not result in greater production of ROS or telomere shortening.http://europepmc.org/articles/PMC3781104?pdf=render |
| spellingShingle | Klelia D Salpea Cecilia G Maubaret Annegret Kathagen Gie Ken-Dror Derek W Gilroy Steve E Humphries The effect of pro-inflammatory conditioning and/or high glucose on telomere shortening of aging fibroblasts. PLoS ONE |
| title | The effect of pro-inflammatory conditioning and/or high glucose on telomere shortening of aging fibroblasts. |
| title_full | The effect of pro-inflammatory conditioning and/or high glucose on telomere shortening of aging fibroblasts. |
| title_fullStr | The effect of pro-inflammatory conditioning and/or high glucose on telomere shortening of aging fibroblasts. |
| title_full_unstemmed | The effect of pro-inflammatory conditioning and/or high glucose on telomere shortening of aging fibroblasts. |
| title_short | The effect of pro-inflammatory conditioning and/or high glucose on telomere shortening of aging fibroblasts. |
| title_sort | effect of pro inflammatory conditioning and or high glucose on telomere shortening of aging fibroblasts |
| url | http://europepmc.org/articles/PMC3781104?pdf=render |
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