Knockout of longevity gene Sirt1 in zebrafish leads to oxidative injury, chronic inflammation, and reduced life span

PloS One
Do Hee KimSeung Woo Park

Abstract

Sirt1, a member of the sirtuin gene family, encodes the most conserved mammalian NAD+-dependent deacetylase enzyme responsible for removing acetyl groups from many proteins. The Sirt1 gene is known as a longevity gene whose knockout in mice leads to decreased lifespan relative to the wild type. This study aimed to explore phenotypic changes in zebrafish Sirt1-knockouts and to investigate the function of the Sirt1 gene. Targeted knockout of Sirt1 in zebrafish (Danio rerio) was achieved using the CRISPR-Cas9 genome editing system. We created a 4-bp insertion-homozygote Sirt1-knockout zebrafish. Although there was no evident difference in appearance in the early stages of development, a significant increase in reactive oxygen species and in the extent of apoptosis in Sirt1-knockout zebrafish was observed. Sirt1 knockout caused inflammatory genes, including IL-1b, IL-6 and TNF-α to be highly expressed. Additionally, the lack of Sirt1 caused chronic inflammation and intestinal atrophy, thereby increasing pro-apoptotic events, which ultimately reduced the lifespan of transgenic zebrafish. Overall, our data demonstrate that lack of Sirt1 caused a significantly increased generation of reactive oxygen species that resulted in chronic in...Continue Reading

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Citations

May 28, 2020·The Journal of Biological Chemistry·Eden A DejeneEdward Seto
Oct 6, 2020·Oxidative Medicine and Cellular Longevity·Fangzhou Jiao, Zuojiong Gong
Jun 3, 2021·Npj Aging and Mechanisms of Disease·Nicholas HolzscheckLars Kaderali
Feb 23, 2020·Mechanisms of Ageing and Development·Cui ChenXiaobo Wang
Aug 19, 2021·Npj Aging and Mechanisms of Disease·Sophie VanhunselLieve Moons
Dec 8, 2020·ACS Chemical Neuroscience·Keng Yoon YeongYuin Chang

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Methods Mentioned

BETA
in vitro transcription
PCR

Software Mentioned

TINA

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