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 journalArticlepeer-review

6 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 languageEnglish (US)
Pages (from-to)268-275
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume77
Issue number2
DOIs
StatePublished - Feb 1 2022

Keywords

  • Caenorhabditis elegans
  • Collagen
  • Naked mole-rat
  • hspb1
  • skn-1

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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