Extended life-span and stress resistance in the Drosophila mutant methuselah.

Toward a genetic dissection of the processes involved in aging, a screen for gene mutations that extend life-span in Drosophila melanogaster was performed. The mutant line methuselah (mth) displayed approximately 35 percent increase in average life-span and enhanced resistance to various forms of stress, including starvation, high temperature, and dietary paraquat, a free-radical generator. The mth gene predicted a protein with homology to several guanosine triphosphate-binding protein-coupled seven-transmembrane domain receptors. Thus, the organism may use signal transduction pathways to modulate stress response and life-span.

[1]  J. Ashby References and Notes , 1999 .

[2]  K. Alitalo,et al.  Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. , 1998, Science.

[3]  G. Lithgow,et al.  Genes That Determine Both Thermotolerance and Rate of Aging in Caenorhabditis elegans a , 1998, Annals of the New York Academy of Sciences.

[4]  A. Elia,et al.  Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons , 1998, Nature Genetics.

[5]  M. Brann,et al.  Structure/function relationships of a G-protein coupling pocket formed by the third intracellular loop of the m5 muscarinic receptor. , 1998, Biochemistry.

[6]  B. Lakowski,et al.  Molecular genetics of life span in C. elegans: how much does it teach us? , 1998, Trends in genetics : TIG.

[7]  T. Sakmar Rhodopsin: a prototypical G protein-coupled receptor. , 1998, Progress in nucleic acid research and molecular biology.

[8]  Marc Tatar,et al.  Chaperoning extended life , 1997, Nature.

[9]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[10]  Koutarou D. Kimura,et al.  daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. , 1997, Science.

[11]  H. Bussey,et al.  Structural and Functional Conservation of the Caenorhabditis elegans Timing Gene clk-1 , 1997, Science.

[12]  J. Tower Aging mechanisms in fruit flies , 1996 .

[13]  G. Ruvkun,et al.  A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans , 1996, Nature.

[14]  P. Vanderhaeghen,et al.  The G Protein–coupled Receptor Family and One of Its Members, the TSH Receptor a , 1995, Annals of the New York Academy of Sciences.

[15]  S. Melov,et al.  Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[16]  T. Johnson,et al.  Thermotolerance of a long-lived mutant of Caenorhabditis elegans. , 1994, Journal of gerontology.

[17]  S. Watson,et al.  The G-Protein Linked Receptor Facts Book , 1994 .

[18]  R. S. Sohal,et al.  Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. , 1994, Science.

[19]  S. Henikoff,et al.  Protein family classification based on searching a database of blocks. , 1994, Genomics.

[20]  C. Kenyon,et al.  A C. elegans mutant that lives twice as long as wild type , 1993, Nature.

[21]  P. L. Larsen Aging and resistance to oxidative damage in Caenorhabditis elegans. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. Vanfleteren Oxidative stress and ageing in Caenorhabditis elegans. , 1993, The Biochemical journal.

[23]  M. Caron,et al.  Mutagenesis of the beta 2-adrenergic receptor: how structure elucidates function. , 1992, Annual review of pharmacology and toxicology.

[24]  G. Baker,et al.  Elevated paraquat resistance can be used as a bioassay for longevity in a genetically based long-lived strain of Drosophila. , 1991, Developmental genetics.

[25]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[26]  T. Uemura,et al.  Searching for pattern and mutation in the Drosophila genome with a P-lacZ vector. , 1989, Genes & development.

[27]  T. Johnson,et al.  A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. , 2002, Genetics.

[28]  J. Nakai,et al.  Location of a region of the muscarinic acetylcholine receptor involved in selective effector coupling , 1988, FEBS letters.

[29]  M. Caron,et al.  Chimeric alpha 2-,beta 2-adrenergic receptors: delineation of domains involved in effector coupling and ligand binding specificity. , 1988, Science.

[30]  A. Spradling,et al.  Insertional mutagenesis of the Drosophila genome with single P elements. , 1988, Science.

[31]  B. Charlesworth,et al.  A test of evolutionary theories of senescence , 1980, Nature.