title: Mutation of C. elegans demethylase spr-5 extends transgenerational longevity.
abstract: Complex organismal properties such as longevity can be transmitted across generations by non-genetic factors. Here we demonstrate that deletion of the C. elegans histone H3 lysine 4 dimethyl (H3K4me2) demethylase, spr-5, causes a trans-generational increase in lifespan. We identify a chromatin-modifying network, which regulates this lifespan extension. We further show that this trans-generational lifespan extension is dependent on a hormonal signaling pathway involving the steroid dafachronic acid, an activator of the nuclear receptor DAF-12. These findings suggest that loss of the demethylase SPR-5 causes H3K4me2 mis-regulation and activation of a known lifespan-regulating signaling pathway, leading to trans-generational lifespan extension.
authors.affiliation: Division of Newborn Medicine, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Eric Lieberman
authors.initials: EL
authors.lastname: Greer
authors.affiliation: Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors.forename: Ben
authors.initials: B
authors.lastname: Becker
authors.affiliation: Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Latza
authors.affiliation: Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Ageing Associated Diseases, University of Cologne, D-50674 Cologne, Germany.
authors.forename: Adam
authors.initials: A
authors.lastname: Antebi
authors.affiliation: Division of Newborn Medicine, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA.|Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002782:Cholestenes / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D056466:Histone Demethylases / Q000235:genetics*; D006657:Histones / Q000235:genetics; D008136:Longevity / Q000235:genetics*; D008745:Methylation; D009154:Mutation / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D002782:Cholestenes; D002843:Chromatin; D006657:Histones; C533800:dafachronic acid; D056466:Histone Demethylases