title: The OLD-1 positive regulator of longevity and stress resistance is under DAF-16 regulation in Caenorhabditis elegans.
abstract: Aging and limited life span are fundamental biological phenomena observed in a variety of species [1]. Approximately 55 genes have been identified that can extend longevity when altered in Caenorhabditis elegans [2-5]. These genes include an insulin-like receptor (daf-2) and a phosphatidylinositol 3-OH kinase (age-1) regulating a forkhead transcription factor (daf-16) [6, 7], as well as genes mediating metabolic throughput [8], sensory perception [9], and reproduction [10]. Moreover, these mutant alleles both extend life span and increase resistance to ultraviolet (UV) radiation [11], heat [12], and oxidative stress [13-15], though the stress resistance of clk-1 is controversial. With the exception of old-1 and perhaps some other genes [16-19], all of the life-extension alleles are hypomorphic or nullomorphic. Here, we show that the OLD-1 transmembrane tyrosine kinase (formerly TKR-1; [16, 20]) is expressed in a variety of tissues, is stress inducible, and is a positive regulator of longevity and stress resistance. The transcription of old-1 is upregulated in long-lived age-1 and daf-2 mutants and is upregulated in response to heat, UV light, and starvation. Both RT-PCR and analysis of an OLD-1::GFP tag suggest that old-1 expression is dependent on daf-16. Importantly, old-1 is required for the life extension of age-1 and daf-2 mutants. This study reveals a new system for specifying longevity and stress resistance and suggests possible mechanisms for mediating life extension by dietary restriction and hormesis.
authors.affiliation: Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA. murakams@umich.edu
authors.forename: S
authors.initials: S
authors.lastname: Murakami
authors.forename: T E
authors.initials: TE
authors.lastname: Johnson
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics / Q000528:radiation effects; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D051858:Forkhead Transcription Factors; D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects; D006361:Heating; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D008136:Longevity; D008565:Membrane Proteins / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D013217:Starvation; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D015801:Helminth Proteins; D008565:Membrane Proteins; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D019869:Phosphatidylinositol 3-Kinases; C442437:tkr-1 protein, C elegans; C100662:AGE-1 protein, C elegans; C107483:DAF-2 protein, C elegans; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin