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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
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Disease relevance of Aging


Psychiatry related information on Aging


High impact information on Aging

  • At the cellular level, p53 induces apoptosis, cell cycle arrest and senescence [11].
  • A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy [12].
  • We identified bes1, a semidominant suppressor of bri1, which exhibits constitutive BR response phenotypes including long and bending petioles, curly leaves, accelerated senescence, and constitutive expression of BR-response genes [13].
  • Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19(ARF)) and is amplified in a subset of human breast cancers [14].
  • In addition, expression of mutant forms of TRF2 induced a growth arrest with characteristics of senescence [15].

Chemical compound and disease context of Aging

  • Src expression increased drug survival in HT1080 fibrosarcoma cells, as measured by the colony formation assay, and strongly inhibited Adriamycin-induced senescence [16].
  • These concentrations of ceramide also induced retinoblastoma dephosphorylation and inhibited serum-induced AP-1 activation in young HDF, thus recapitulating basic biochemical and molecular changes of senescence [17].
  • Expression of ipt, a cytokinin biosynthetic gene from Agrobacterium tumefaciens, under the control of the promoter from a senescence-associated gene (SAG12) has been one approach used to delay senescence [18].
  • METHODS: Several different chronic conditions were studied in rats: senescence, hypertension, chronic hypoxia, and administration of thyroid hormone [19].
  • The results suggest that both ABA and cytokinins are involved in controlling plant senescence, and an enhanced carbon remobilization is attributed to an elevated ABA level in rice plants subjected to water stress [20].

Biological context of Aging


Anatomical context of Aging


Associations of Aging with chemical compounds


Gene context of Aging

  • Thus, Cdk4 deficiency causes senescence in a unique Arf/p53-independent manner, which accounts for the loss of transformation potential [36].
  • A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19(ARF)-p53 signaling [37].
  • We made a large library containing random mutations in the amino terminus of the EST2 gene, which encodes the Saccharomyces cerevisiae TERT, and selected functional alleles by their ability to rescue senescence of telomerase-negative cells [38].
  • Senescence, aging, and malignant transformation mediated by p53 in mice lacking the Brca1 full-length isoform [39].
  • WS fibroblasts display defects associated with telomere dysfunction, including accelerated telomere erosion and premature senescence [40].

Analytical, diagnostic and therapeutic context of Aging


  1. Increased mitochondrial oxidative stress in the Sod2 (+/-) mouse results in the age-related decline of mitochondrial function culminating in increased apoptosis. Kokoszka, J.E., Coskun, P., Esposito, L.A., Wallace, D.C. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  2. Normal human fibroblasts are resistant to RAS-induced senescence. Benanti, J.A., Galloway, D.A. Mol. Cell. Biol. (2004) [Pubmed]
  3. Manganese superoxide dismutase induces p53-dependent senescence in colorectal cancer cells. Behrend, L., Mohr, A., Dick, T., Zwacka, R.M. Mol. Cell. Biol. (2005) [Pubmed]
  4. Human fibroblast commitment to a senescence-like state in response to histone deacetylase inhibitors is cell cycle dependent. Ogryzko, V.V., Hirai, T.H., Russanova, V.R., Barbie, D.A., Howard, B.H. Mol. Cell. Biol. (1996) [Pubmed]
  5. Immortalization by c-myc, H-ras, and Ela oncogenes induces differential cellular gene expression and growth factor responses. Kelekar, A., Cole, M.D. Mol. Cell. Biol. (1987) [Pubmed]
  6. Cloning and chromosomal location of a novel member of the myotonic dystrophy family of protein kinases. Zhao, Y., Loyer, P., Li, H., Valentine, V., Kidd, V., Kraft, A.S. J. Biol. Chem. (1997) [Pubmed]
  7. High levels of brain dolichols in neuronal ceroid-lipofuscinosis and senescence. Ng Ying Kin, N.M., Palo, J., Haltia, M., Wolfe, L.S. J. Neurochem. (1983) [Pubmed]
  8. Reexamination of the relationship between alcohol preference and brain monoamines in inbred strains of mice including senescence-accelerated mice. Yoshimoto, K., Komura, S. Pharmacol. Biochem. Behav. (1987) [Pubmed]
  9. Simultaneous electrochemiluminescence determination of sulpiride and tiapride by capillary electrophoresis with cyclodextrin additives. Li, J., Zhao, F., Ju, H. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. (2006) [Pubmed]
  10. Biogenic monoamine uptake by rat brain synaptosomes during aging. Effects of nootropic drugs. Stancheva, S.L., Alova, L.G. Gen. Pharmacol. (1994) [Pubmed]
  11. Chromosome stability, in the absence of apoptosis, is critical for suppression of tumorigenesis in Trp53 mutant mice. Liu, G., Parant, J.M., Lang, G., Chau, P., Chavez-Reyes, A., El-Naggar, A.K., Multani, A., Chang, S., Lozano, G. Nat. Genet. (2004) [Pubmed]
  12. A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Schmitt, C.A., Fridman, J.S., Yang, M., Lee, S., Baranov, E., Hoffman, R.M., Lowe, S.W. Cell (2002) [Pubmed]
  13. BES1 accumulates in the nucleus in response to brassinosteroids to regulate gene expression and promote stem elongation. Yin, Y., Wang, Z.Y., Mora-Garcia, S., Li, J., Yoshida, S., Asami, T., Chory, J. Cell (2002) [Pubmed]
  14. Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19(ARF)) and is amplified in a subset of human breast cancers. Jacobs, J.J., Keblusek, P., Robanus-Maandag, E., Kristel, P., Lingbeek, M., Nederlof, P.M., van Welsem, T., van de Vijver, M.J., Koh, E.Y., Daley, G.Q., van Lohuizen, M. Nat. Genet. (2000) [Pubmed]
  15. TRF2 protects human telomeres from end-to-end fusions. van Steensel, B., Smogorzewska, A., de Lange, T. Cell (1998) [Pubmed]
  16. Src inhibits adriamycin-induced senescence and G2 checkpoint arrest by blocking the induction of p21waf1. Vigneron, A., Roninson, I.B., Gamelin, E., Coqueret, O. Cancer Res. (2005) [Pubmed]
  17. Role of ceramide in cellular senescence. Venable, M.E., Lee, J.Y., Smyth, M.J., Bielawska, A., Obeid, L.M. J. Biol. Chem. (1995) [Pubmed]
  18. Overproduction of cytokinins in petunia flowers transformed with P(SAG12)-IPT delays corolla senescence and decreases sensitivity to ethylene. Chang, H., Jones, M.L., Banowetz, G.M., Clark, D.G. Plant Physiol. (2003) [Pubmed]
  19. Energy metabolism patterns in mammalian myocardium adapted to chronic physiopathological conditions. Rossi, A., Lortet, S. Cardiovasc. Res. (1996) [Pubmed]
  20. Abscisic acid and cytokinins in the root exudates and leaves and their relationship to senescence and remobilization of carbon reserves in rice subjected to water stress during grain filling. Yang, J., Zhang, J., Wang, Z., Zhu, Q., Liu, L. Planta (2002) [Pubmed]
  21. Telomeres shorten during ageing of human fibroblasts. Harley, C.B., Futcher, A.B., Greider, C.W. Nature (1990) [Pubmed]
  22. A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Morris, J.Z., Tissenbaum, H.A., Ruvkun, G. Nature (1996) [Pubmed]
  23. Telomerase catalytic subunit homologs from fission yeast and human. Nakamura, T.M., Morin, G.B., Chapman, K.B., Weinrich, S.L., Andrews, W.H., Lingner, J., Harley, C.B., Cech, T.R. Science (1997) [Pubmed]
  24. Endoplasmic reticulum stress induces p53 cytoplasmic localization and prevents p53-dependent apoptosis by a pathway involving glycogen synthase kinase-3beta. Qu, L., Huang, S., Baltzis, D., Rivas-Estilla, A.M., Pluquet, O., Hatzoglou, M., Koumenis, C., Taya, Y., Yoshimura, A., Koromilas, A.E. Genes Dev. (2004) [Pubmed]
  25. Smurf2 up-regulation activates telomere-dependent senescence. Zhang, H., Cohen, S.N. Genes Dev. (2004) [Pubmed]
  26. Extension of the life-span of human endothelial cells by an interleukin-1 alpha antisense oligomer. Maier, J.A., Voulalas, P., Roeder, D., Maciag, T. Science (1990) [Pubmed]
  27. Senescence of human fibroblasts induced by oncogenic Raf. Zhu, J., Woods, D., McMahon, M., Bishop, J.M. Genes Dev. (1998) [Pubmed]
  28. Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Molofsky, A.V., He, S., Bydon, M., Morrison, S.J., Pardal, R. Genes Dev. (2005) [Pubmed]
  29. Modeling mutations in the G1 arrest pathway in human gliomas: overexpression of CDK4 but not loss of INK4a-ARF induces hyperploidy in cultured mouse astrocytes. Holland, E.C., Hively, W.P., Gallo, V., Varmus, H.E. Genes Dev. (1998) [Pubmed]
  30. p16(Ink4a) in melanocyte senescence and differentiation. Sviderskaya, E.V., Hill, S.P., Evans-Whipp, T.J., Chin, L., Orlow, S.J., Easty, D.J., Cheong, S.C., Beach, D., DePinho, R.A., Bennett, D.C. J. Natl. Cancer Inst. (2002) [Pubmed]
  31. Ethylene: a gaseous signal molecule in plants. Bleecker, A.B., Kende, H. Annu. Rev. Cell Dev. Biol. (2000) [Pubmed]
  32. Inhibition of leaf senescence by autoregulated production of cytokinin. Gan, S., Amasino, R.M. Science (1995) [Pubmed]
  33. Brain acetylcholine synthesis declines with senescence. Gibson, G.E., Peterson, C., Jenden, D.J. Science (1981) [Pubmed]
  34. Structural mechanism of the bromodomain of the coactivator CBP in p53 transcriptional activation. Mujtaba, S., He, Y., Zeng, L., Yan, S., Plotnikova, O., Sachchidanand, n.u.l.l., Sanchez, R., Zeleznik-Le, N.J., Ronai, Z., Zhou, M.M. Mol. Cell (2004) [Pubmed]
  35. p53-dependent ceramide response to genotoxic stress. Dbaibo, G.S., Pushkareva, M.Y., Rachid, R.A., Alter, N., Smyth, M.J., Obeid, L.M., Hannun, Y.A. J. Clin. Invest. (1998) [Pubmed]
  36. Cdk4 disruption renders primary mouse cells resistant to oncogenic transformation, leading to Arf/p53-independent senescence. Zou, X., Ray, D., Aziyu, A., Christov, K., Boiko, A.D., Gudkov, A.V., Kiyokawa, H. Genes Dev. (2002) [Pubmed]
  37. A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19(ARF)-p53 signaling. Shvarts, A., Brummelkamp, T.R., Scheeren, F., Koh, E., Daley, G.Q., Spits, H., Bernards, R. Genes Dev. (2002) [Pubmed]
  38. Essential functions of amino-terminal domains in the yeast telomerase catalytic subunit revealed by selection for viable mutants. Friedman, K.L., Cech, T.R. Genes Dev. (1999) [Pubmed]
  39. Senescence, aging, and malignant transformation mediated by p53 in mice lacking the Brca1 full-length isoform. Cao, L., Li, W., Kim, S., Brodie, S.G., Deng, C.X. Genes Dev. (2003) [Pubmed]
  40. The Werner syndrome helicase and exonuclease cooperate to resolve telomeric D loops in a manner regulated by TRF1 and TRF2. Opresko, P.L., Otterlei, M., Graakjaer, J., Bruheim, P., Dawut, L., Kølvraa, S., May, A., Seidman, M.M., Bohr, V.A. Mol. Cell (2004) [Pubmed]
  41. Enhanced expression of an insulin growth factor-like binding protein (mac25) in senescent human mammary epithelial cells and induced expression with retinoic acid. Swisshelm, K., Ryan, K., Tsuchiya, K., Sager, R. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  42. Isolation and characterization of senescence-induced cDNAs encoding deoxyhypusine synthase and eucaryotic translation initiation factor 5A from tomato. Wang, T.W., Lu, L., Wang, D., Thompson, J.E. J. Biol. Chem. (2001) [Pubmed]
  43. Tandem orientation of duplicated xanthine dehydrogenase genes from Arabidopsis thaliana: differential gene expression and enzyme activities. Hesberg, C., Hänsch, R., Mendel, R.R., Bittner, F. J. Biol. Chem. (2004) [Pubmed]
  44. Inhibition of the phosphoinositide 3-kinase pathway induces a senescence-like arrest mediated by p27Kip1. Collado, M., Medema, R.H., Garcia-Cao, I., Dubuisson, M.L., Barradas, M., Glassford, J., Rivas, C., Burgering, B.M., Serrano, M., Lam, E.W. J. Biol. Chem. (2000) [Pubmed]
  45. Molecular cloning and nucleotide sequence of cDNA for murine senile amyloid protein: nucleotide substitutions found in apolipoprotein A-II cDNA of senescence accelerated mouse (SAM). Kunisada, T., Higuchi, K., Aota, S., Takeda, T., Yamagishi, H. Nucleic Acids Res. (1986) [Pubmed]
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