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

• Published in: The journals of gerontology. Series A, Biological sciences and medical sciences Vol. 77; no. 2; pp. 268 - 275
• Main Authors: Alexander, Courtney Carroll, Munkáscy, Erin, Tillmon, Haven, Fraker, Tamara, Scheirer, Jessica, Holstein, Deborah, Lozano, Damian, Khan, Maruf, Gidalevitz, Tali, Lechleiter, James D, Fisher, Alfred L, Zare, Habil, Rodriguez, Karl A
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 03-02-2022
• Subjects: Animals; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Collagen; Gene expression; Genes; Heat shock proteins; Heat transfer; Heat-Shock Response - genetics; HSF1 protein; Hsp25 protein; Hsp27 protein; Life span; Longevity - genetics; Oxidative stress; Oxidative Stress - physiology; Pharynx; Proteins; RNA-mediated interference; Stress; THE JOURNAL OF GERONTOLOGY: Biological Sciences; Transcription factors; Naked mole-rat; hspb1; skn-1; Collagen; Caenorhabditis elegans
• ISSN: 1079-5006; 1758-535X
• DOI: 10.1093/gerona/glab296

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.