کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8284782 | 1535601 | 2016 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
C. elegans lifespan extension by osmotic stress requires FUdR, base excision repair, FOXO, and sirtuins
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
Moderate stress can increase lifespan by hormesis, a beneficial low-level induction of stress response pathways. 5â²-fluorodeoxyuridine (FUdR) is commonly used to sterilize Caenorhabditis elegans in aging experiments. However, FUdR alters lifespan in some genotypes and induces resistance to thermal and proteotoxic stress. We report that hypertonic stress in combination with FUdR treatment or inhibition of the FUdR target thymidylate synthase, TYMS-1, extends C. elegans lifespan by up to 30%. By contrast, in the absence of FUdR, hypertonic stress decreases lifespan. Adaptation to hypertonic stress requires diminished Notch signaling and loss of Notch co-ligands leads to lifespan extension only in combination with FUdR. Either FUdR treatment or TYMS-1 loss induced resistance to acute hypertonic stress, anoxia, and thermal stress. FUdR treatment increased expression of DAF-16 FOXO and the osmolyte biosynthesis enzyme GPDH-1. FUdR-induced hypertonic stress resistance was partially dependent on sirtuins and base excision repair (BER) pathways, while FUdR-induced lifespan extension under hypertonic stress conditions requires DAF-16, BER, and sirtuin function. Combined, these results demonstrate that FUdR, through inhibition of TYMS-1, activates stress response pathways in somatic tissues to confer hormetic resistance to acute and chronic stress. C. elegans lifespan studies using FUdR may need re-interpretation in light of this work.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mechanisms of Ageing and Development - Volume 154, March 2016, Pages 30-42
Journal: Mechanisms of Ageing and Development - Volume 154, March 2016, Pages 30-42
نویسندگان
Edward N. Anderson, Mark E. Corkins, Jia-Cheng Li, Komudi Singh, Sadé Parsons, Tim M. Tucey, Altar Sorkaç, Huiyan Huang, Maria Dimitriadi, David A. Sinclair, Anne C. Hart,