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

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

doi:10.1093/gerona/glab296

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

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

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

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.

Original language	English (US)
Pages (from-to)	268-275
Number of pages	8
Journal	Journals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume	77
Issue number	2
DOIs	https://doi.org/10.1093/gerona/glab296
State	Published - Feb 1 2022

Keywords

Caenorhabditis elegans
Collagen
Naked mole-rat
hspb1
skn-1

ASJC Scopus subject areas

General Medicine

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10.1093/gerona/glab296

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Alexander, C. C., Munkáscy, E., Tillmon, H., Fraker, T., Scheirer, J., Holstein, D., Lozano, D., Khan, M., Gidalevitz, T., Lechleiter, J. D., Fisher, A. L., Zare, H., & Rodriguez, K. A. (2022). HspB1 Overexpression Improves Life Span and Stress Resistance in an Invertebrate Model. Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 77(2), 268-275. https://doi.org/10.1093/gerona/glab296

Alexander, CC, Munkáscy, E, Tillmon, H, Fraker, T, Scheirer, J, Holstein, D, Lozano, D, Khan, M, Gidalevitz, T, Lechleiter, JD, Fisher, AL, Zare, H & Rodriguez, KA 2022, 'HspB1 Overexpression Improves Life Span and Stress Resistance in an Invertebrate Model', Journals of Gerontology - Series A Biological Sciences and Medical Sciences, vol. 77, no. 2, pp. 268-275. https://doi.org/10.1093/gerona/glab296

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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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AU - Khan, Maruf

AU - Gidalevitz, Tali

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

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