HspB1 Overexpression Improves Life Span and Stress Resistance in an Invertebrate Model

HspB1 过表达可延长无脊椎动物的寿命并提高其抗逆性

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作者:Courtney Carroll Alexander, Erin Munkáscy, Haven Tillmon, Tamara Fraker, Jessica Scheirer, Deborah Holstein, Damian Lozano, Maruf Khan, Tali Gidalevitz, James D Lechleiter, Alfred L Fisher, Habil Zare, Karl A Rodriguez

Abstract

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.

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