DhHP-6 extends lifespan of Caenorhabditis elegans by enhancing nuclear translocation and transcriptional activity of DAF-16

Abstract

Earlier studies have demonstrated that Deuterohaemin-AlaHisThrValGluLys (DhHP-6), a novel porphyrin-peptide, increases lifespan and enhances stress resistance of Caenorhabditis elegans. To explore the possible mechanisms, in this study we investigated the roles of SIR-2.1 and DAF-16 in DhHP-6's function using wild-type and various other mutant strains of C. elegans. DhHP-6's effect was dependent upon DAF-16, and it did not extend the lifespan of the loss-of-function daf-16 mutant strain (daf-16(mu86) I). DhHP-6 enhanced DAF-16 translocation from cytoplasm to nuclei; and it increased DAF-16's transcriptional activity, likely by activating the SIR-2.1/DAF-16 complex. DhHP-6's effect was also dependent upon SIR-2.1, and it did not increase the lifespan of the worms with SIR-2.1 deacetylase activity inhibited by niacin amide (SIR-2.1 inhibitor) and SIR-2.1 RNA interference (RNAi). Niacin amide and RNAi increased DAF-16‘s nuclear localization; but they decreased DAF-16's transcriptional activity, likely by preventing the formation of the SIR-2.1/DAF-16 complex. These results suggest that DhHP-6 extends the lifespan of C. elegans via SIR 2.1 and DAF-16, and they provide new insights into the molecular mechanisms of aging.

Keywords::

• ROS
• daf-16
• sir-2.1
• nuclear translocation
• lifespan
• Caenorhabditis elegans

Acknowledgements

We thank Professor Xueqi Fu of College of Life Science of J.L.University for providing research materials and technical instructions. The GFP pictures of sod-3::gfp(muIs84) mutant were taken with the assistance of Professor Xuexun Fang from the Key Laboratory for Molecular Enzymology and Engineering. Fluorescence quantifications were assisted by Professor Yingjie Guo from College of Life Science of J.L.University. We thank Professor Yuhong Wang for helpful suggestions and critical review of the manuscript. A special thanks to the Caenorhabditis Genetics Center (CGC), which is funded by the National Institutes of Health – National Center for Research Resources, for some of the nematode strains.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

This study was supported by JL-NSFC 201015171? YYZX201150-2?201205017; 12SF23. Some nematode strains used in this work were provided by Caenorhabditis Genetics Center, which is funded by the National Institutes of Health (NIH) National Center for Research Resources.