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HspB1 Overexpression Improves Life Span and Stress Resistance in an Invertebrate Model
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences ( IF 4.3 ) Pub Date : 2021-10-06 , DOI: 10.1093/gerona/glab296
Courtney Carroll Alexander 1, 2, 3 , Erin Munkáscy 1, 2 , Haven Tillmon 1 , Tamara Fraker 1, 2 , Jessica Scheirer 1, 2 , Deborah Holstein 2 , Damian Lozano 2 , Maruf Khan 2 , Tali Gidalevitz 4 , James D Lechleiter 2 , Alfred L Fisher 5 , Habil Zare 2, 6 , Karl A Rodriguez 1, 2
Affiliation  

To explore the role of the small heat shock protein beta 1 (HspB1, also known as Hsp25 in rodents and Hsp27 in humans) in longevity, we created a Caenorhabiditis elegans model with a high level of ubiquitous expression of the naked mole-rat HspB1 protein. The worms showed increased life span under multiple conditions and also increased resistance to heat stress. RNAi experiments suggest that HspB1-induced life extension is dependent on the transcription factors skn-1 (Nrf2) and hsf-1 (Hsf1). RNAseq from HspB1 worms showed an enrichment in several skn-1 target genes, including collagen proteins and lysosomal genes. Expression of HspB1 also improved functional outcomes regulated by SKN-1, specifically oxidative stress resistance and pharyngeal integrity. This work is the first to link a small heat shock protein with collagen function, suggesting a novel role for HspB1 as a hub between canonical heat response signaling and SKN-1 transcription.

中文翻译:

HspB1 过度表达可提高无脊椎动物模型的寿命和抗压能力

为了探索小热休克蛋白 beta 1(HspB1,在啮齿动物中也称为 Hsp25,在人类中也称为 Hsp27)在长寿中的作用,我们创建了一个高水平普遍表达裸鼹鼠 HspB1 蛋白的秀丽隐杆线虫模型. 这些蠕虫在多种条件下显示出更长的寿命,并且还增加了对热应激的抵抗力。RNAi 实验表明 HspB1 诱导的寿命延长依赖于转录因子 skn-1 (Nrf2) 和 hsf-1 (Hsf1)。来自 HspB1 蠕虫的 RNAseq 显示了几个 skn-1 靶基因的富集,包括胶原蛋白和溶酶体基因。HspB1 的表达还改善了由 SKN-1 调节的功能结果,特别是抗氧化应激和咽部完整性。这项工作是第一个将小热休克蛋白与胶原蛋白功能联系起来,
更新日期:2021-10-06
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