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Gene Review

Life1  -  lifespan variability, 1

Mus musculus

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Disease relevance of Life1

  • We have recently shown that vesicular stomatitis virus (VSV) exhibits potent oncolytic activity both in vitro and in vivo (S. Balachandran and G. N. Barber, IUBMB Life 50:135-138, 2000) [1].
  • BACKGROUND: Life-threatening cardiac arrhythmia is a major source of mortality worldwide [2].
  • Diabetic patients have shorter life span and poorer Quality of Life mainly due to diabetic vascular complications [3].
  • It fundamental toxicological data in mice and rats were assessed; its antitumor activity was investigated by establishing in mice, inoculated with L 1210 leukemia or in AKR mice with spontaneous leukemia of viral origin, a significant increase in Mean Survival Time as well as a percent increase of Increased Life Span and of the number of survivors [4].

Psychiatry related information on Life1

  • In a previous paper [Sakai et al., Life Sciences, 48, 2397-2404 (1991)], we showed that thioperamide, a histamine H3 antagonist, which enhances the release of histamine from histaminergic neurons, in doses of 12.5 and 25 mg/kg, i.p. increases the locomotor activity, whereas it decreases the brain histamine content [5].

High impact information on Life1

  • Cell biology. Life without caveolae [6].
  • Transforming Growth Factor-beta: Taking Control of T Cells' Life and Death [7].
  • Physiology of murine B lymphocytes. I. Life-spans of anti-mu and haptenated Ficoll (thymus-independent antigen)-reactive B cells [8].
  • 4-hydroxy-tamoxifen the bladder was processed for X-Gal (Life Technologies, Rockville, Maryland) staining [9].
  • Our recent study demonstrated that ginsenosides had antinociceptive effects by reducing some types of pain-related behavior in mice (Yoon et al., 1998. Ginsenosides induce differential antinociception and inhibit substance P-induced nociceptive response in mice. Life Science 62, PL319-PL325) [10].

Biological context of Life1

  • The Alternatives to Carcinogenicity Testing Committee of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) conducted a large-scale, multinational collaborative research program to evaluate several genetically modified mouse assays for assessing the human carcinogenic potential of compounds [11].
  • To this end, we are participating in an International Life Sciences Institute (ILSI) project involving studies of gene expression changes caused by model genotoxins [12].
  • The multi-lab International Life Sciences Institute (ILSI) project on the application of genomics to risk assessment offered the unique opportunity to investigate the influence of variability within and between laboratories on identifying biologically relevant gene expression changes [13].
  • We have demonstrated that seizures induced by kainic acid (KA) are, at least in part, mediated via oxidative stress in rats [Life. Sci. 61 (1997) PL373; Brain Res. 853 (2000) 215; Brain Res. 874 (2000) 15; Neurosci. Lett. 281 (2000) 65] [14].
  • National Workshop on Astrobiology: The Life Science Involvement of AAS-I Laben [15].

Anatomical context of Life1

  • This finding supports biochemical studies that detected high levels of iron in white matter (Hallgren and Sourander, J Neurochem 3:41-51, 1958) and myelin fractions of brain homogenates (Rajan et al., Life Sci 18:423-432, 1976) [16].
  • In an earlier report we have described how the administration of reserpine (0.5 mg/kg) stimulates the peroxidase activity of rat and mouse submaxillary gland [R. Chakraborty, B. Mukherjee and R. N. Hati, Life Sci. 35, 1913 (1984)] [17].
  • Small lymphocytes in peripheral lymphoid tissues of nude mice. Life-span and distribution [18].
  • The physicochemical and biological properties of a mouse hepatocyte growth-stimulating factor (mHGSF), whose amount in mouse serum increased markedly 24 h after carbon tetrachloride administration (E. Gohda et al., Life Sci. 46, 1801 (1990)), were examined [19].
  • This study was conducted as part of the International Life Sciences Institute (ILSI) program to evaluate the carcinogenic potential of clofibrate, a nongenotoxic, peroxisome proliferator-activated receptor (PPAR) alpha agonist following oral administration to Tg.AC (transgenic) and wild-type FVB (nontransgenic) mice for a minimum for 6 months [20].

Associations of Life1 with chemical compounds

  • The original planned program on immunity was expanded to incorporate a session on a closely related topic "Alcohol and Mitochondrial Metabolism: At the Crossroads of Life and Death" organized by Dr. Jan Hoek and Dr. Sam Zakhari [21].
  • Ochnaflavone (OC), a naturally occurring biflavonoid with anti-inflammatory activity [S.J. Lee, J.H. Choi, H.W. Chang, S.S. Kang, H.P. Kim. Life Sci. 57(6), 1995, 551-558], was isolated from Lonicera japonica and its effects on inducible nitric oxide synthase (iNOS) gene expression was examined in RAW264.7 cells [22].
  • In the biochemical study, a previous report showed that thioperamide accelerated the release of neuronal histamine in the brains of mice [Sakai et al., Life Sciences, 48, 2397-2404(1991)] [23].
  • The results of this study are at variance with those reported by Klemm & Foster (Life Sci., 1986, 39, 897-902) who described a sharp decrease of the total level of brain gangliosides after injection of a single dose of ethanol [24].

Analytical, diagnostic and therapeutic context of Life1

  • BACKGROUND: Life-long immunosuppression is a major cause of mortality and morbidity in transplant recipients [25].
  • In this context of the utility of mechanistic data for human cancer risk assessment, the International Life Sciences Institute (ILSI) has developed a human relevance framework (HRF) that can be used to assess the plausibility of a mode of action (MoA) described for animal models operating in humans [26].
  • Studies conducted under the auspices of International Life Sciences Institute (ILSI) have suggested that an alternative mouse carcinogenicity study may be substituted for the traditional 2-year mouse bioassay typically conducted to support the development of drug candidates [27].
  • This survey on biotechnology and bioethics was carried out on national random samples of the public and scientists in November 2000-January 2000 [sic]throughout Japan, and attendees at the Novartis Life Science Forum held on 29 September 1999 in Tokyo. The sample size was 297, 370, and 74 respectively [28].


  1. Oncolytic activity of vesicular stomatitis virus is effective against tumors exhibiting aberrant p53, Ras, or myc function and involves the induction of apoptosis. Balachandran, S., Porosnicu, M., Barber, G.N. J. Virol. (2001) [Pubmed]
  2. Conditional mineralocorticoid receptor expression in the heart leads to life-threatening arrhythmias. Ouvrard-Pascaud, A., Sainte-Marie, Y., Bénitah, J.P., Perrier, R., Soukaseum, C., Cat, A.N., Royer, A., Le Quang, K., Charpentier, F., Demolombe, S., Mechta-Grigoriou, F., Beggah, A.T., Maison-Blanche, P., Oblin, M.E., Delcayre, C., Fishman, G.I., Farman, N., Escoubet, B., Jaisser, F. Circulation (2005) [Pubmed]
  3. Roles of the receptor for advanced glycation endproducts in diabetes-induced vascular injury. Yonekura, H., Yamamoto, Y., Sakurai, S., Watanabe, T., Yamamoto, H. J. Pharmacol. Sci. (2005) [Pubmed]
  4. Synthesis, acute toxicity and chemotherapeutic anti-cancer activities of a new tripeptidic mustard. De Barbieri, A., Dall'Asta, L., Comini, A., Springolo, V., Mosconi, P., Coppi, G. Il Farmaco; edizione scientifica. (1983) [Pubmed]
  5. Effects of (S)-alpha -fluoromethylhistidine and metoprine on locomotor activity and brain histamine content in mice. Sakai, N., Onodera, K., Maeyama, K., Yanai, K., Watanabe, T. Life Sci. (1992) [Pubmed]
  6. Cell biology. Life without caveolae. Parton, R.G. Science (2001) [Pubmed]
  7. Transforming Growth Factor-beta: Taking Control of T Cells' Life and Death. Horwitz, D.A. Immunity (2006) [Pubmed]
  8. Physiology of murine B lymphocytes. I. Life-spans of anti-mu and haptenated Ficoll (thymus-independent antigen)-reactive B cells. Udhayakumar, V., Goud, S.N., Subbarao, B. Eur. J. Immunol. (1988) [Pubmed]
  9. Controlling gene expression in the urothelium using transgenic mice with inducible bladder specific Cre-lox recombination. Bex, A., Vooijs, M., Horenblas, S., Berns, A. J. Urol. (2002) [Pubmed]
  10. Effect of ginsenosides, active components of ginseng, on capsaicin-induced pain-related behavior. Nah, J.J., Hahn, J.H., Chung, S., Choi, S., Kim, Y.I., Nah, S.Y. Neuropharmacology (2000) [Pubmed]
  11. The utility of genetically modified mouse assays for identifying human carcinogens: a basic understanding and path forward. The Alternatives to Carcinogenicity Testing Committee ILSI HESI. MacDonald, J., French, J.E., Gerson, R.J., Goodman, J., Inoue, T., Jacobs, A., Kasper, P., Keller, D., Lavin, A., Long, G., McCullough, B., Sistare, F.D., Storer, R., van der Laan, J.W. Toxicol. Sci. (2004) [Pubmed]
  12. Identification of a gene expression profile that discriminates indirect-acting genotoxins from direct-acting genotoxins. Hu, T., Gibson, D.P., Carr, G.J., Torontali, S.M., Tiesman, J.P., Chaney, J.G., Aardema, M.J. Mutat. Res. (2004) [Pubmed]
  13. Laboratory variability does not preclude identification of biological functions impacted by hydroxyurea. Müller, A., Boitier, E., Hu, T., Carr, G.J., Le Fèvre, A.C., Marchandeau, J.P., Flor, M., Jefferson, F., Aardema, M.J., Thybaud, V. Environ. Mol. Mutagen. (2005) [Pubmed]
  14. Oxidative damage causes formation of lipofuscin-like substances in the hippocampus of the senescence-accelerated mouse after kainate treatment. Kim, H.C., Bing, G., Jhoo, W.K., Kim, W.K., Shin, E.J., Park, E.S., Choi, Y.S., Lee, D.W., Shin, C.Y., Ryu, J.R., Ko, K.H. Behav. Brain Res. (2002) [Pubmed]
  15. National Workshop on Astrobiology: The Life Science Involvement of AAS-I Laben. Adami, G. Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life (2006) [Pubmed]
  16. Oligodendrocytes and myelin sheaths in normal, quaking and shiverer brains are enriched in iron. LeVine, S.M. J. Neurosci. Res. (1991) [Pubmed]
  17. Studies on the effect of reserpine on the peroxidase activity of submaxillary gland. Chakraborty, R., Hati, R.N. Biochem. Pharmacol. (1986) [Pubmed]
  18. Small lymphocytes in peripheral lymphoid tissues of nude mice. Life-span and distribution. Hougen, H.P., Röpke, C. Clin. Exp. Immunol. (1975) [Pubmed]
  19. Characterization of a mouse hepatocyte growth-stimulating factor in serum of mice treated with carbon tetrachloride. Hayashi, Y., Yamamoto, I., Gohda, E. Chem. Pharm. Bull. (1992) [Pubmed]
  20. Evaluation of the carcinogenic potential of clofibrate in the FVB/Tg.AC mouse after oral administration--part I. Torrey, C.E., Wall, H.G., Campbell, J.A., Kwanyuen, P., Hoivik, D.J., Miller, R.T., Allen, J.S., Jayo, M.J., Selinger, K., Savina, P.M., Santostefano, M.J. International journal of toxicology. (2005) [Pubmed]
  21. RSA 2004: combined basic research satellite symposium-mechanisms of alcohol-mediated organ and tissue damage: inflammation and immunity and alcohol and mitochondrial metabolism: at the crossroads of life and death session one: alcohol, cellular and organ damage. Hoek, J., Thiele, G.M., Klassen, L.W., Mandrekar, P., Zakhari, S., Cook, R.T., Ray, N.B., Happel, K.I., Kolls, J.K., Kovacs, E.J., Szab, G. Alcohol. Clin. Exp. Res. (2005) [Pubmed]
  22. The naturally occurring biflavonoid, ochnaflavone, inhibits LPS-induced iNOS expression, which is mediated by ERK1/2 via NF-kappaB regulation, in RAW264.7 cells. Suh, S.J., Chung, T.W., Son, M.J., Kim, S.H., Moon, T.C., Son, K.H., Kim, H.P., Chang, H.W., Kim, C.H. Arch. Biochem. Biophys. (2006) [Pubmed]
  23. The behavioral and biochemical effects of thioperamide, a histamine H3-receptor antagonist, in a light/dark test measuring anxiety in mice. Imaizumi, M., Onodera, K. Life Sci. (1993) [Pubmed]
  24. Lack of major effects of ethanol, chlorpromazine, hexobarbital and haloperidol on brain gangliosides. Miller-Podraza, H., Rakowska, M., Skarzyńska, E. Acta Biochim. Pol. (1990) [Pubmed]
  25. Tolerance induced without immunosuppression in a T-lymphocyte suicide-gene therapy cardiac allograft model in mice. Braunberger, E., Raynal-Raschilas, N., Thomas-Vaslin, V., Bruneval, P., Fabiani, J.N., Carpentier, A., Glotz, D., Klatzmann, D. J. Thorac. Cardiovasc. Surg. (2000) [Pubmed]
  26. Cancer risk assessment for 1,3-butadiene: Data integration opportunities. Preston, R.J. Chem. Biol. Interact. (2007) [Pubmed]
  27. Studies evaluating the utility of N-methyl-N-nitrosourea as a positive control in carcinogenicity studies in the p53+/- mouse. Hoivik, D.J., Allen, J.S., Wall, H.G., Nold, J.B., Miller, R.T., Santostefano, M.J. International journal of toxicology. (2005) [Pubmed]
  28. Attitudes of the public and scientists to biotechnology in Japan at the start of 2000. Ng, M.A., Takeda, C., Watanabe, T., Macer, D. Eubios journal of Asian and international bioethics : EJAIB. (2000) [Pubmed]
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