title: 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.
authors: College of Life Science, Jilin University, Changchun, China.
authors: Lei
authors: L
authors: Huang
authors: Pengfei
authors: P
authors: Li
authors: Guan
authors: G
authors: Wang
authors: Shuwen
authors: S
authors: Guan
authors: Xiaoli
authors: X
authors: Sun
authors: Liping
authors: L
authors: Wang
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors; D006427:Hemin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008136:Longevity / Q000187:drug effects*; D009842:Oligopeptides / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D037761:Sirtuins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D009842:Oligopeptides; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C552681:deuterohemin-alanyl-histidyl-threonyl-valyl-glutamyl-lysine; D006427:Hemin; C507014:SIR-2.1 protein, C elegans; D037761:Sirtuins