title: PAK1-deficiency/down-regulation reduces brood size, activates HSP16.2 gene and extends lifespan in Caenorhabditis elegans.
abstract: There is an increasing evidence that the oncogenic kinase PAK1 is responsible not only for malignant transformation, but also for several other diseases such as inflammatory diseases (asthma and arthritis), infectious diseases including malaria, AIDS, and flu, as well as a series of neuronal diseases/disorders (neurofibromatosis, tuberous sclerosis, Alzheimer's diseases, Huntington's disease, epilepsy, depression, learning deficit, etc.) which often cause premature death. Interestingly, a few natural PAK1-blockers such as curcumin, caffeic acid (CA) and rosmarinic acid (RA) extend the lifespan of the nematode Caenorhabditis elegans or fruit flies. Here, to explore the possibility that C. elegans could provide us with a quick and inexpensive in vivo screening system for a series of more potent but safe (non-toxic) PAK1-blocking therapeutics, we examined the effects of PAK1-deficiency or down-regulation on a few selected functions of this worm, including reproduction, expression of HSP16.2 gene, and lifespan. In short, we found that PAK1 promotes reproduction, whereas it inactivates HSP16.2 gene and shortens lifespan, as do PI-3 kinase (AGE-1), TOR, and insulin-like signalling /ILS (Daf-2) in this worm. These findings not only support the "trade-off" theory on reproduction versus lifespan, but also suggest the possibility that the reduced reproduction (or HSP16.2 gene activation) of this worm could be used as the first indicator of extended lifespan for a quick in vivo screening for PAK1-blockers.
authors.affiliation: Daito-Bunka University, Saitama, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yanase
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.forename: H
authors.initials: H
authors.lastname: Maruta
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002109:Caffeic Acids / Q000494:pharmacology; D015536:Down-Regulation; D049452:Green Fluorescent Proteins / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics*; D008136:Longevity / Q000187:drug effects / Q000235:genetics*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D010666:Phenylpropionates / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012098:Reproduction / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D054462:p21-Activated Kinases / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D002109:Caffeic Acids; D006360:Heat-Shock Proteins; D010666:Phenylpropionates; D047428:Protein Kinase Inhibitors; D011993:Recombinant Fusion Proteins; C108431:hsp-16.2 protein, C elegans; D049452:Green Fluorescent Proteins; C102259:artepillin C; D054462:p21-Activated Kinases; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol