Temporal requirements of heat shock factor-1 for longevity assurance.
Temporal requirements of heat shock factor-1 for longevity assurance.
复制标题
DOI：
10.1111/j.1474-9726.2012.00811.x
复制
发表时间：
2012-06
期刊：
影响因子：
7.8
通讯作者：
Dillin A
中科院分区：
文献类型：
--
作者：
Volovik Y;Maman M;Dubnikov T;Bejerano-Sagie M;Joyce D;Kapernick EA;Cohen E;Dillin A
降低胰岛素/IGF-1信号通路（IIS）的活性可以改变发育，提高应激抵抗力，防止有毒蛋白质聚集（蛋白质毒性），并延长蠕虫、苍蝇和小鼠的寿命。秀丽隐杆线虫（C. elegans），通过IIS减少延长寿命完全依赖于转录因子β-16和热休克因子-1（HSF-1）的活性。虽然β-16仅在成年早期决定寿命，但在成年后期也需要蛋白毒性保护。相比之下，HSF-1在幼虫发育期间保护免受蛋白毒性。尽管对HSF-1的寿命延长的关键要求，该转录因子作为寿命决定因素的时间要求是未知的。为了确定HSF-1对长寿保证的时间要求，我们在幼虫发育和成虫期有条件地敲低了HSF-1。发现与DAF-16不同，HSF-1是在早期幼虫发育期间决定寿命所最需要的，在早期成年期间需要的程度较低，并且在成年后期对寿命也具有很小的影响。我们的研究结果表明，早期发育事件影响寿命，并表明HSF-1在发育过程中设置的条件，使β-16在生殖成年期促进长寿。这项研究提出了一种新的HSF-1和IIS的长寿功能之间的联系。
Reducing the activity of the Insulin/IGF-1 Signaling pathway (IIS) modifies development, elevates stress resistance, protects from toxic protein aggregation (proteotoxicity) and extends lifespan of worms, flies and mice. In the nematode Caenorhabditis elegans (C. elegans), lifespan extension by IIS reduction is entirely dependent upon the activity of the transcription factors DAF-16 and the Heat Shock Factor-1 (HSF-1). While DAF-16 determines lifespan exclusively during early adulthood it is required for proteotoxicity protection also during late adulthood. In contrast, HSF-1 protects from proteotoxicity during larval development. Despite the critical requirement for HSF-1 for lifespan extension the temporal requirements for this transcription factor as a lifespan determinant are unknown. To establish the temporal requirements of HSF-1 for longevity assurance we conditionally knocked down hsf-1 during larval development and adulthood of C. elegans and found that unlike daf-16, hsf-1 is foremost required for lifespan determination during early larval development, required for a lesser extent during early adulthood and has small effect on longevity also during late adulthood. Our findings indicate that early developmental events affect lifespan and suggest that HSF-1 sets during development the conditions that enable DAF-16 to promote longevity during reproductive adulthood. This study proposes a novel link between HSF-1 and the longevity functions of the IIS.
登录
查看更多内容
影响因子：
9.8
作者：
David DC;Ollikainen N;Trinidad JC;Cary MP;Burlingame AL;Kenyon C
通讯作者：
Kenyon C
影响因子：
56.9
作者：
Knight, SW;Bass, BL
通讯作者：
Bass, BL
影响因子：
56.9
作者：
Boehm, M;Slack, F
通讯作者：
Slack, F
影响因子：
56.9
作者：
RABINDRAN, SK;HAROUN, RI;WU, C
通讯作者：
WU, C
影响因子：
7.8
作者：
Giannakou, Maria E.;Goss, Martin;Partridge, Linda
通讯作者：
Partridge, Linda