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

Journals of Gerontology - Series A Biological Sciences and Medical Sciences, ISSN: 1758-535X, Vol: 77, Issue: 2, Page: 268-275
2022
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Article Description

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.

Bibliographic Details

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; Rozalyn M Anderson

Oxford University Press (OUP)

Medicine

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