The genetics of aging

Annual Review of Genomics and Human Genetics

Volumn 2, Issue , 2001, Pages 435-462

  Finch, Caleb E ^a   Ruvkun, Gary ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

Longevity; Metabolism; Phylogeny; Polymorphism; Senescence

Indexed keywords

FREE RADICAL; HORMONE; INSULIN; PROTEIN; PROTEIN AGE 1; PROTEIN AKT 1; PROTEIN DAF 11; PROTEIN DAF 18; PROTEIN DAF 2; PROTEIN DAF 3; PROTEIN DAF 7; PROTEIN KINASE B; PROTEIN KINASE B BETA; PROTEIN PDK 1; TRANSCRIPTION FACTOR DAF 16; UNCLASSIFIED DRUG;

AGING; CAENORHABDITIS; CALORIC RESTRICTION; DROSOPHILA; EXPRESSED SEQUENCE TAG; GENE CONTROL; GENE EXPRESSION; GENETIC ANALYSIS; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GENETICS; HIBERNATION; HORMONE RELEASE; INSULIN LIKE ACTIVITY; INSULIN RELEASE; LIFESPAN; LONGEVITY; MAMMAL; METABOLISM; METAZOON; MOLECULAR MODEL; MORTALITY; NERVE CELL; NERVOUS SYSTEM; NEUROSECRETORY CELL; PEDIGREE; PHYLOGENY; REPRODUCTION; REVIEW; SENESCENCE; SIGNAL TRANSDUCTION; SLEEP; SPECIES DIFFERENCE; STRESS; YEAST;

AGING; ANIMALS; HUMANS; PHYLOGENY; POLYMORPHISM, GENETIC;

ANIMALIA; CAENORHABDITIS; CAENORHABDITIS ELEGANS; INVERTEBRATA; MAMMALIA; METAZOA;

EID: 0035775614     PISSN: 15278204     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.genom.2.1.435     Document Type: Review

References (130)

1. Alessi DR, Andjelkovic M, Caudwell B, Cron P, Morrice N, et al. 1996. Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J. 15:6541-51
2. Alessi DR, James SR, Downes CP, Holmes AB, Gaffney PRJ, et al. 1997. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B. Curr. Biol. 7:261-69
3. Apfeld J, Kenyon C. 1999. Regulation of life span by sensory perception in Caenorhabditis elegans. Nature 402:804-9
4. Bargmann CI. 1998. Neurobiology of the Caenorhabditis elegans genome. Science 282:2028-33
5. Bargmann CI, Horvitz HR. 1991. Control of larval development by chemosensory neurons in Caenorhabditis elegans. Science 251:1243-46
6. Bartke A, Brown-Borg HM, Bode AM, Carlson J, Hunter WS, Bronson RT. 1998. Does growth hormone prevent or accelerate aging? Exp. Gerontol. 33:675-87
7. Birnby DA, Link EM, Vowels JJ, Tian H, Colacurcio PL, Thomas JH. 2000. A transmembrane guanylyl cyclase (DAF-11) and Hsp90 (DAF-21) regulate a common set of chemosensory behaviors in Caenorhabditis elegans. Genetics 155:85-104
8. Blander G, Zalle N, Leal JF, Bar-Or RL, Yu CE, Oren M. 2000. The Werner syndrome protein contributes to induction of p53 by DNA damage. FASEB J. 14:2138-40
9. Brody JA, Grant MD, Frateschi LJ, Miller SC, Zhang H. 2000. Reproductive longevity and increased life expectancy. Age Aging 29:75-78
10. Brogiolo W, Stocker H, Ikeya T, Rintelen F, Fernandez R, Hafen E. 2001. Curr. Biol. 11:213-21
11. Brown-Borg HM, Borg KE, Meliska CJ, Bartke A. 1996. Dwarf mice and the ageing process. Nature 384:330
12. Bruning JC, Gautam D, Burks DJ, Gillette J, Schubert M, et al. 2000. Role of brain insulin receptor in control of body weight and reproduction. Science 289: 2122-25
13. Carey JR, Judge DS. 2000. Longevity Records: Life Spans of Mammals, Birds, Amphibians, Reptiles, and Fish, Monographs on Population Aging, Vol. 8. Odense: Odense University Press. 241 pp.
14. Castro E, Ogburn CE, Hunt KE, Tilvis R, Louhija J, et al. 1999. Polymorphisms at the Werner locus: I. Newly identified polymorphisms, ethnic variability of 1367Cys/Arg, and its stability in a population of Finnish centenarians. Am. J. Med. Genet. 82:399-403
15. Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, et al. 2001. Extension of life span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 292:104-6
16. Colman PD, Kaplan BB, Osterburg HH, Finch CE. 1980. Brain poly(A)RNA during aging: Stability of yield and sequence complexity in two rat strains. J. Neurochem. 34:335-45
17. Coschigano KT, Clemmons D, Bellush LL, Kopchick JJ. 2000. Assessment of growth parameters and life span of GHR/ BP gene-disrupted mice. Endocrinology 141:2608-13
18. Curtsinger JW, Fukui HH, Resler AS, Kelly K, Khazaeli AA. 1998. Genetic analysis of extended life span in Drosophila melanogaster. I. RAPD screen for genetic divergence between selected and control lines. Genetica 104:21-32
19. De Haan G, Van Zant G. 1999. Genetic analysis of hemopoietic cell cycling in mice suggests its involvement in organismal life span. FASEB J. 13:707-13
20. Devi G, Ottman R, Tang M, Marder K, Stern Y, et al. 1999. Influence of APOE genotype on familial aggregation of AD in an urban population. Neurology 53:789-94
21. Do KA, Broom BM, Kuhert P, Duffy DL, Todorov AA, et al. 2000. Genetic analysis of the age at menopause by using estimating equations and Bayesian random effects models. Stat. Med. 19:1217-35
22. Dorman JB, Albinder B, Shroyer T, Kenyon C. 1995. The age-1 and daf-2 genes function in a common pathway to control the life span of Caenorhabditis elegans. Genetics 141:1399-406
23. Durham SK, Suwanichkul A, Scheimann AO, Yee D, Jackson JG, et al. 1999. FKHR binds the insulin response element in the insulin-like growth factor binding protein-1 promoter. Endocrinology 140:3140-46
24. Eigenmann JE, Amador A, Patterson DF. 1988. Insulin-like growth factor I levels in proportionate dogs, chondrodystrophic dogs, and giant dogs. Acta Endocrinol. 106:448-53
25. Estevez M, Attisano L, Wrana JL, Albert PS, Massague J, Riddle DL. 1993. The daf-4 gene encodes a bone morphogenetic protein receptor controlling C. elegans dauer larva development. Nature 365:644-49
26. Fabrizio P, Pozza F, Pletcher S, Gendron CM, Longo VD. 2001. Regulation of longevity and stress resistance by Sch9 in yeast. Science 292:288-90
27. Falconer DS, Mackay TFC. 1996. Introduction to Quantitative Genetics. London: Longman. 464 pp. 4th ed.
28. Felkai S, Ewbank JJ, Lemieux J, Labbe JC, Brown GG, Hekimi S. 1999. CLK-1 controls respiration, behavior and aging in the nematode Caenorhabditis elegans. EMBO J. 18:1783-92
29. Finch CE. 1990. Longevity, Senescence, and the Genome. Chicago: Univ. Chicago Press. 922 pp.
30. Finch CE. 1994. Commentary on latent capacities for gametogenic cycling in the semelparous invertebrate Nereis. Proc. Natl. Acad. Sci. USA 91:11769-70
31. Finch CE, Austad SN. 2001. Organisms with slow aging. Exp. Gerontol. 36(Spec. issue)
32. Finch CE, Kirkwood TBL. 2000. Chance, Development, and Aging. New York: Oxford Univ. Press. 278 pp.
33. Finch CE, Morgan TE, Rozovsky I, Xie Z, Weindruch R, Prolla T. 2001. Microglia and aging in the brain. In Microglia in the Degenerating and Regenerating CNS, ed. WJ Streit. New York: Springer-Verlag. In press
34. Finch CE, Rose MR. 1995. Hormones and the physiological architecture of life history evolution. Q. Rev. Biol. 70:1-52
35. Finch CE, Tanzi RE. 1997. Genetics of aging. Science 278:407-11
36. Gems D, Sutton AJ, Sundermeyer ML, Albert PS, King KV, et al. 1998. Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. Genetics 150:129-55
37. George JC, Bada J, Zeh J, Brown SE, O'Hara T, Suydam R. 1999. Age and growth estimates of bowhead whales (Balaena mysticetus) via aspartic acid racemization. Can. J. Zool. 77:571-80
38. Georgi LL, Albert PS, Riddle DL. 1990. daf-1, a C. elegans gene controlling dauer larva development, encodes a novel receptor protein kinase. Cell 61:635-45
39. Gerdes LU, Jeune B, Ranberg KA, Nybo H, Vaupel JW. 2000. Estimation of apolipoprotein E genotype-specific relative mortality risks from the distribution of genotypes in centenarians and middle-aged men: Apolipoprotein E gene is a "frailty gene", not a "longevity gene". Genet. Epidemiol. 19:202-10
40. Golden JW, Riddle DL. 1984. A pheromone-induced developmental switch in Caenorhabditis elegans: Temperature-sensitive mutants reveal a wild-type temperature-dependent process. Proc. Natl. Acad. Sci. USA 81:819-23
41. Gottlieb S, Ruvkun G. 1994. daf-2, daf-16, and daf-23: Genetically interacting genes controlling dauer formation in Caenorhabditis elegans. Genetics 137: 107-20
42. Granner D, Andreone T, Sasaki K, Beale E. 1983. Inhibition of transcription of the phosphoenolpyruvate carboxykinase gene by insulin. Nature 305:549-51
43. Guarente L, Kenyon C. 2000. Genetic pathways that regulate aging in model organisms. Nature 408:255-62
44. Gudmundsson H, Gudbjartsson DF, Frigge M, Gulcher JR, Stefansson K. 2000. Inheritance of human longevity in Iceland. Eur. J. Hum. Genet. 8:743-49
45. Guo S, Rena G, Cichy S, He X, Cohen P, Uterman T. 1999. Phosphorylation of serine 256 by proteiun kinase B disrupts transactivation by FKHR and mediates effects of insulin on insulin-like growth factor-binding protein-1 promoter activity through a conserved insulin response sequence. J. Biol. Chem. 174:17184-92
46. Hall RK, Yamasaki T, Kucera T, Waltner-Law M, Obrien R, Granner DK. 2000. Regulation of phosphoenolpyruvate carboxykinase and insulin-like growth factor-binding protein-1 gene expression by insulin. The role of winged helix/forkhead proteins. J. Biol. Chem. 275:30169-75
47. Hauck SJ, Bartke A. 2000. Effects of growth hormone on hypothalamic catalase and Cu/Zn superoxide dismutase. Free Radic. Biol. Med. 28:970-78
48. Heijmans BT, Westendorp RG, Slagboom PE. 2000. Common gene variants, mortality and extreme longevity in humans. Exp. Gerontol. 35:865-77
49. Herskind AM, McGue M, Holm NV, Sorensen TI, Harvald B, Vaupel JW. 1996. The heritability of human long-evity: A population-based study of 2872 Danish twin pairs born 1870-1900. Hum. Genet. 97:319-23
50. Hobert O, Mori I, Yamashita Y, Honda H, Ohshima Y, et al. 1997. Regulation of interneuron function in the C. elegans thermoregulatory pathway by the ttx-3 LIM homeobox gene. Neuron 19:345-57
51. Honda Y, Honda S. 1999. The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J. 13:1385-93
52. Huang TT, Carlson EJ, Gillespie AM, Shi Y, Epstein CJ. 2000. Ubiquitous over-expression of CuZn superoxide dismutase does not extend life span in mice. J. Gerontol. A 55:B5-B9
53. Inoue T, Thomas JH. 2000. Targets of TGF-beta signaling in Caenorhabditis elegans dauer formation. Dev. Biol. 217: 192-204
54. Ishii N, Fujii M, Hartman PS, Tsuda M, Yasuda K, et al. 1998. A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and aging in nematodes. Nature 394:694-97
55. Jonassen T, Larsen PL, Clarke CF. 2001. A dietary source of coenzyme Q is essential for growth of long-lived Caenorhabditis elegans clk-1 mutants. Proc. Natl. Acad. Sci. USA 98:421-26
56. Kalantaridou SN, Davis SR, Nelson LM. 1998. Premature ovarian failure. Endocrinol. Metab. Clin. N. Am. 27:989-1006
57. Kenyon C, Chang J, Gensch E, Rudner A, Tabtlang R. 1993. A C. elegans mutant that lives twice as long as wild type. Nature 366:461-64
58. Kimura KH, Tissenbaum A, Liu Y, Ruvkun G. 1997. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277:942-46
59. Kirkwood TB, Austad SN. 2000. Why do we age? Nature 408:233-38
60. Klass M. 1983. A method for the isolation of longevity mutants in the nematode C. elegans and initial results. Mech. Aging Dev. 22:279-86
61. Krishna S, Maduzia LL, Padgett RW. 1999. Specificity of TGF-beta signaling is conferred by distinct type I receptors and their associated SMAD proteins in Caenorhabditis elegans. Development 126:251-60
62. Kubisch HM, Wang J, Bray TM, Phillips JP. 1997. Targeted overexpression of Cu/Zn superoxide dismutase protects pancreatic beta-cells against oxidative stress. Diabetes 46:1563-66
63. Kulkarni RN, Brüning JC, Winnay JN, Postic C, Magnuson MA, Kahn CR. 1999. Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 96:329-39
64. Kurapati R, Passananti HB, Rose MR, Tower J. 2000. Increased hsp22 RNA levels in Drosophila lines genetically selected for increased longevity. J. Gerontol. A 55:B552-59
65. Lakowski B, Hekimi S. 1998. The genetics of caloric restriction in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 95:13091-96
66. Larsen P. 1993. Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 90:8905-9
67. Larsen PL, Albert PS, Riddle DL. 1995. Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics 139:1567-83
68. Lebovitz RM, Zhang H, Vogel H, Cartwright J Jr, Dionne L, et al. 1996. Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proc. Natl. Acad. Sci. USA 93:9782-87
69. Lee CK, Klopp RG, Weindruch R, Prolla TA. 1999. Gene expression profile of aging and its retardation by caloric restriction. Science 285:1390-93
70. Lee CK, Weindruch R, Prolla TA. 2000. Gene-expression profile of the aging brain in mice. Nat. Genet. 25:294-97
71. Lin YJ, Seroude L, Benzer S. 1998. Extended life span and stress resistance in the Drosophila mutant methuselah. Science 282:943-46
72. Lithgow GJ, White TM, Melov S, Johnson TE. 1995. Thermotolerance and extended life span conferred by single-gene mutations and induced by thermal stress. Proc. Natl. Acad. Sci. USA 92:7540-44
73. Ljungquist B, Berg S, Lanke J, McClearn GE, Pedersen NL. 1998. The effect of genetic factors for longevity: A comparison of identical and fraternal twins in the Swedish Twin Registry. J. Gerontol. A 53:M441-46
74. Lombard DB, Beard C, Johnson B, Marciniak RA, Dausman J, et al. 2000. Mutations in the WRN gene in mice accelerate mortality in a p53-null background. Mol. Cell. Biol. 20:3286-91
75. Martin GM, Oshima J. 2000. Lessons from human progeroid syndromes. Nature 408:263-66
76. Melov S, Ravenscroft J, Malik S, Gill MS, Walker DW, et al. 2000. Extension of life span with superoxide dismutase/ catalase mimetics. Science 289:1567-69
77. Meyer MR, Tschanz JT, Norton MC, Welsh-Bohmer KA, Steffencs DC, et al. 1998. APOE genotype predicts when - Not whether - One is predisposed to develop Alzheimer disease. Nat. Genet. 19:321-22
78. Michael MD, Kulkarni RN, Postic C, Previs SF, Shulman GI, et al. 2000. Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol. Cell 6:87-97
79. Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, et al. 1999. The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402:309-13
80. Miller RA. 1999. Kleemeier Award Lecture: Are there genes for aging? J. Gerontol. A 54:B297-307
81. Miller RA, Chrisp C, Atchley W. 2000. Differential longevity in mouse stocks selected for early life growth trajectory. J. Gerontol. A 55:B455-61
82. Miller RM. 2001. Biomarkers and genetics of aging in mice. In Cells and Surveys: Should Biomarkers Be Included in Social Science Research?, ed. CE Finch, JW Vaupel, K Kinsella, 8:180-212. Washington, DC: Natl. Acad. 347 pp.
83. Morgan TE, Xie Z, Goldsmith S, Yoshida T, Lanzrein AS, et al. 1999. The mosaic of brain glial hyperactivity during normal aging and its attenuation by food restriction. Neuroscience 89:687-99
84. Morris JZ, Tissenbaum HA, Ruvkun G. 1996. A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382:536-39
85. Nakae J, Park BC, Accili D. 1999. Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on serine 253 through a Wortmannin-sensitive pathway. J. Biol. Chem. 274:15982-85
86. Nasrin N, Ogg S, Cahill C, Biggs W, Nui S, et al. 2000. DAF-16 recruits the CBP co-activator to the IGFBP-1 promoter in HepG2 cells. Proc. Natl. Acad. Sci. USA 97:10412-17
87. Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, et al. 1997. The fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389:994-99
88. Ogg S, Ruvkun G. 1998. The C. elegans PTEN homolog daf-18 acts in the insulin receptor-like metabolic signaling pathway. Mol. Cell 2:887-93
89. Oldham S, Bohni R, Stocker H, Brogiolo W, Hafen E. 2000. Genetic control of size in Drosophila. Philos. Trans. R. Soc. Lond. B 355:945-52
90. Paradis S, Ruvkun G. 1998. Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor 67. Genes Dev. 12:2488-98
91. Paradis S, Ailion M, Toker A, Thomas JH, Ruvkun G. 1999. A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in C. elegans. Genes Dev. 13: 1438-52
92. Parkes TL, Elia AJ, Dickinson D, Hilliker AJ, Phillips JP, Boulianne GL. 1998. Extension of Drosophila life span by over-expression of human SOD1 in motorneurons. Nat. Genet. 19:171-74
93. Patterson G, Koweek A, Wong A, Liu Y, Ruvkun G. 1997. The DAF-3 Smad protein antagonizes TGF-beta-related receptor signaling in the Caenorhabditis elegans dauer pathway. Genes Dev. 11:2679-90
94. Perls TT, Alpert L, Fretts RC. 1997. Middle-aged mothers live longer. Nature 389:133
95. Perls TT, Shea-Drinkwater M, Bowen-Flynn J, Ridge SB, Kang S, et al. 2000. Exceptional familial clustering for extreme longevity in humans. J. Am. Geriatr. Soc. 48:1483-85
96. Perls TT, Silver MH, Lauerman JT. 2000. Living to 100: Lessons in Living to Your Maximum Potential at Any Age. New York: Basic Books. 272 pp.
97. Pierce SB, Costa M, Wisotzkey R, Devadhar S, Homburger SA, et al. 2001. Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. Genes Dev. 15:672-86
98. Ren P, Lim C-S, Johnsen R, Albert PS, Pilgrim D, Riddle DL. 1996. Control of C. elegans larval development by neuronal expression of a TGF-beta homolog. Science 274:1389-92
99. Rena G, Guo S, Cichy SC, Unterman TG, Cohen P. 1999. Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. J. Biol. Chem. 274:17179-83
100. Reveillaud I, Niedzwiecki A, Bensch KG, Fleming JE. 1991. Expression of bovine superoxide dismutase in Drosophila melanogaster augments resistance of oxidative stress. Mol. Cell. Biol. 11:632-40
101. Rogina B, Reenan RA, Nilsen SP, Helfand S. 2000. Extended life span conferred by cotransporter gene mutations in Drosophila. Science 290:2137-40
102. Rose MR, Mueller LD. 2000. Ageing and immortality. Philos. Trans. R. Soc. Lond. B 355:1657-62
103. Rose MR, Vu LN, Park SU, Graves JL Jr. 1992. Selection on stress resistance increases longevity in Drosophila melanogaster. Exp. Gerontol. 27:241-50
104. Schachter F, Faure-Delanef L, Guenot F, Rouger H, Froguel P, et al. 1994. Genetic associations with human longevity at the APOE and ACE loci. Nat. Genet. 6:29-32
105. Schackwitz WS, Inoue T, Thomas JH. 1996. Chemosensory neurons function in parallel to mediate a pheromone response in C. elegans. Neuron 17:719-28
106. Schmidt PS, Duvernell DD, Eanes WF. 2000. Adaptive evolution of a candidate gene for aging in Drosophila. Proc. Natl. Acad. Sci. USA 97:10861-65
107. Schmoll D, Walker KS, Alessi DR, Grempler R, Burchell A, et al. 2000. Regulation of glucose-6-phosphatase gene expression by protein kinase B-alpha and the forkhead transcription factor FKHR: Evidence for insulin response unit (IRU)-dependent and independent effects of insulin on promoter activity. J. Biol. Chem. 275:36324-33
108. Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. 2000. Central nervous system control of food intake. Nature 404:661-71
109. Shefner JM, Reaume AG, Flood DG, Scott RW, Kowall NW, et al. 1999. Mice lacking cytosolic copper/zinc superoxide dismutase display a distinctive motor axonopathy. Neurology 53:1239-46
110. Smith JD. 2000. Apolipoprotein E4: An allele associated with many diseases. Ann. Med. 32:118-27
111. Sneider H, MacGregor AJ, Spector TD. 1998. Genes control the cessation of a woman's reproductive life: A twin study of hysterectomy and age at menopause. J. Clin. Endocrinol. Metab. 83:1875-80
112. Sohal RS, Weindruch R. 1996. Oxidative stress, caloric restriction, and aging. Science 273:59-63
113. Stengard JH, Weiss KM, Sing CF. 1998. An ecological study of association between coronary heart disease mortality rates in men and the relative frequencies of common allelic variations in the gene coding for apolipoprotein E. Hum. Genet. 103:234-41
114. Sze JY, Victor M, Loer C, Shi Y, Ruvkun G. 2000. Food and metabolic signaling defects in a C. elegans serotonin null mutant. Nature 403:560-64
115. Takagi Y, Mitsui A, Nishiyama A, Nozaki K, Sono H, et al. 1999. Over-expression of thioredoxin in transgenic mice attenuates focal ischemic brain damage. Proc. Natl. Acad. Sci. USA 96:4131-36
116. Tang ED, Nunez G, Barr FG, Guan KL, 1999. Negative regulation of the forkhead transcription factor FKHR by Akt. J. Biol. Chem. 274:16741-46
117. Tartar M, Kopelman A, Epstein D, Tu MP, Yin CM, Garofalo RS. 2001. A mutant Drosophila insulin receptor homolog that extends life span and impairs neuroendocrine function. Science 292:107-10
118. Taub J, Lau JF, Ma C, Hahn JH, Hoque R, et al. 1999. A cytosolic catalase is needed to extend adult lifespan in C. elegans dauer constitutive and clk-1 mutants. Nature 399:162-66
119. Tauber MJ, Tauber CA, Masaki S. 1986. Seasonal Adaptation of Insects. New York: Oxford Univ. Press. 411pp.
120. Thomas JH, Birnby DA, Vowels JJ. 1993. Evidence for parallel processing of sensory information controlling dauer formation in Caenorhabditis elegans. Genetics 134:1005-117
121. Tissenbaum HA, Guarente L. 2001. Increased dosage of a sir-2 gene extends life span in Caenorhabditis elegans. Nature. In press
122. Tissenbaum HA, Ruvkun G. 1998. An insulin-like signaling pathway affects both longevity and reproduction in Caenorhabditis elegans. Genetics 148:703-17
123. Tomizawa M, Kumar A, Perrot V, Nakae J, Accili D, et al. 2000. Insulin inhibits the activation of transcription by a C-terminal fragment of the forkhead transcription factor FKHR. A mechanism for insulin inhibition of insulin-like growth factor-binding protein-1 transcription. J. Biol. Chem. 275:7289-95
124. Vanfleteren JR, De Vreese A. 1995. The gerontogenes age-1 and daf-2 determine metabolic rate potential in aging Caenorhabditis elegans. FASEB J. 9:1355-61
125. Van Voorhies WA, Ward S. 1999. Genetic and environmental conditions that increase longevity in Caenorhabditis elegans decrease metabolic rate. Proc. Natl. Acad. Sci. USA 96:11399-403
126. Vieira C, Pasyukova EG, Zeng ZB, Hackett JB, Lyman RF, Mackay TF. 2000. Genotype-environment interaction for quantitative trait loci affecting life span in Drosophila melanogaster. Genetics 154:213-27
127. Wang P, Chen H, Qin H, Sankarapandi S, Becher MW, et al. 1998. Overexpression of human copper, zinc-superoxide dismutase (SOD1) prevents postischemic injury. Proc. Natl. Acad. Sci. USA 95:4556-60
128. Wise PM, Smith MJ, Dubal DB, Wilson ME, Krajnak KM, Rosewell KL. 1999. Neuroendocrine influences and repercussions of the menopause. Endocr. Rev. 20:243-48
129. Wolkow CA, Kimura KD, Lee MS, Ruvkun G. 2000. Regulation of C. elegans life span by insulinlike signaling in the nervous system. Science 290:147-50
130. Wong PC, Rothstein JD, Price DL. 1998. The genetic and molecular mechanisms of motor neuron disease. Curr. Opin. Neurobiol. 8:791-99