The age of heterozygosity.

Age
Audrey CarrièreSiegfried Hekimi

Abstract

Two mutant mouse models of longevity in which the loss of only one copy of the gene leads to a significantly increased lifespan have recently been described: Igf1r (+/-) and mclk1 (+/-). Igf1r encodes a transmembrane receptor kinase for the insulin-like growth factor-1, and mclk1 encodes a hydroxylase that is necessary for the biosynthesis of ubiquinone. Interestingly, the motivation for testing the longevity of both of these mutants came from observations in the nematode Caenorhabditis elegans. IGF-1R protein is homologous to DAF-2 and mCLK1 is the mouse orthologue of the C. elegans enzyme CLK-1. In worms, the homozygous inactivation of both of these longevity genes is viable and no dominant mutations are known. In addition to aging slowly, old mclk1 (+/-) mice were found to undergo loss-of-heterozygosity at the mclk1 locus, which results in clones of mclk1 (-/-) cells in the liver, presumably because mclk1 (-/-) cells can outcompete mclk1 (+/-) cells under certain conditions. We will discuss how these observations suggest novel directions of research, but also call for some caution in the interpretation of past and future results.

References

May 1, 1973·Journal of the National Cancer Institute·G S SmithM R Mickey
Dec 2, 1993·Nature·C KenyonR Tabtiang
Nov 7, 1996·Nature·H M Brown-BorgA Bartke
Feb 10, 1999·Experimental Gerontology·S M Jazwinski
Jan 29, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·R BranickyS Hekimi
Jan 3, 2001·Proceedings of the National Academy of Sciences of the United States of America·T JonassenC F Clarke
Feb 13, 2001·Experimental Gerontology·A BartkeC Wright
Mar 13, 2001·The Journal of Biological Chemistry·H MiyaderaK Kita
Mar 22, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·D BarsyteG J Lithgow
Oct 5, 2001·Trends in Genetics : TIG·P DevileeC J Cornelisse
Oct 5, 2001·The Journal of Biological Chemistry·F LevavasseurS Hekimi
Dec 17, 2002·Nature·Martin HolzenbergerYves Le Bouc
Jan 25, 2003·Science·Matthias BlüherC Ronald Kahn
Dec 31, 2003·Experimental Gerontology·Hanyu LiangArlan Richardson
Jan 28, 2004·Cell·Charles J Sherr
Jul 19, 2005·Physiology·João Pedro de Magalhães, George M Church

❮ Previous
Next ❯

Citations

May 7, 2009·Lipids in Health and Disease·Bryan G Hughes, Siegfried Hekimi
Aug 8, 2006·Experimental Gerontology·Zaruhi StepanyanSiegfried Hekimi
Aug 31, 2006·Nature Genetics·Siegfried Hekimi
Mar 27, 2012·PLoS Biology·Michael N Tennison, Jonathan D Moreno
Sep 17, 2013·Neuromodulation : Journal of the International Neuromodulation Society·Gun-Marie Hariz, Katarina Hamberg

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.