CRISPR-activated expression of collagen col-120 increases lifespan and heat tolerance
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2023
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Journal Article
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Abstract
Transgenic overexpression of collagen col-120 increases the lifespan of C. elegans. However, whether post-developmental enhancement of collagen expression could also increase the lifespan is unknown. Recently, we described a method to induce the expression of a target gene using catalytically dead Cas9 (dCas9)-engineered C. elegans via ingestion of bacteria expressing a pair of promoter-specific single guide RNAs (sgRNA). Here, we cloned col-120 promoter-specific sgRNA oligo pair into L4440-Biobrick-sgRNA and fed these bacteria to dCas9::VP64 transgenic C. elegans. We observed a similar percentage of lifespan extension by post-developmentally dCas9-induced expression of col-120, as previously reported through transgenic overexpression of col-120. Consistent with this result is that induction of another previously shown longevity-promoting collagen, col-10, also increased lifespan. Furthermore, we found an enhanced resilience to heat stress and increased expression of hsp-16.2 upon dCas9-activated col-120 expression. Together, these results provide an orthogonal method to validate longevity by enhancing col-120 expression and point towards a potential role of collagen enhancement in thermotolerance.
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published
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Caltech Library
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09598 - Ewald, Collin Y. (ehemalig) / Ewald, Collin Y. (former)
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190072 - Protein homeostasis of extracellular proteins during aging (SNF)