Molecular mechanisms of age-related regulation of genes

Kotoku Kurachi, Sumiko Kurachi, Kezhong Zhang, Afshin Ameri, Jeffrey Huo, Mitsuhiro Kuwahara, Jean Marc Fontaine, Takahiro Abe

Research output: Contribution to journalArticle

Abstract

Through transgenic mouse analyses of age-related expression of human genes, we recently discovered the first molecular mechanism of age-related regulation of gene expression, a critical finding for understanding the age-dimension homeostasis. In our study, human genes for blood coagulation factor IX (FIX) and anti-coagulant protein C (PC), which show age-dependent increasing and stable expression patterns, respectively, were subjected to systematic in vitro and in vivo analyses. The mechanism found uses two genetic elements, age-related stability elements (ASEs, G/CAGGAAG) and age-related increase element (AIE, a stretch of dinucleotide repeats). ASE is required for age-related stable patterns of gene expression as seen for the human PC (hPC) gene, whereas a combination of ASE and AIE is required for age-related increase patterns of gene expression as seen for the human FIX gene. ASE functions not only for temporal regulation but also for precise spatial regulation of gene expression. Differential and combined usages of ASE and AIE apparently generate specific age-related regulatory patterns of different genes. Transgenic mice persistently over-expressing hFIX at high levels died at much younger ages than expected. These animals developed not only thromboses in tissues such as heart, brain and lung but also generated myocardial fibrosis in the left ventricle, mimicking a type of human myocardial infarction. These findings laid the foundation for developing a new research field, age-dimension technology (ADT), which explores useful applications of the mechanisms of age-dimension homeostasis.

Original languageEnglish (US)
Pages (from-to)562-565
Number of pages4
JournalInternational Congress Series
Volume1262
Issue numberC
DOIs
StatePublished - May 1 2004
Externally publishedYes

Fingerprint

Factor IX
Genes
Gene Expression Regulation
Protein C
Gene Expression
Transgenic Mice
Homeostasis
Dinucleotide Repeats
Coagulants
Heart Ventricles
Thrombosis
Fibrosis
Myocardial Infarction
Technology
Lung
Brain
Research
In Vitro Techniques

Keywords

  • Age-dimension technology
  • Age-related regulation of genes
  • Molecular

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kurachi, K., Kurachi, S., Zhang, K., Ameri, A., Huo, J., Kuwahara, M., ... Abe, T. (2004). Molecular mechanisms of age-related regulation of genes. International Congress Series, 1262(C), 562-565. https://doi.org/10.1016/j.ics.2004.02.166

Molecular mechanisms of age-related regulation of genes. / Kurachi, Kotoku; Kurachi, Sumiko; Zhang, Kezhong; Ameri, Afshin; Huo, Jeffrey; Kuwahara, Mitsuhiro; Fontaine, Jean Marc; Abe, Takahiro.

In: International Congress Series, Vol. 1262, No. C, 01.05.2004, p. 562-565.

Research output: Contribution to journalArticle

Kurachi, K, Kurachi, S, Zhang, K, Ameri, A, Huo, J, Kuwahara, M, Fontaine, JM & Abe, T 2004, 'Molecular mechanisms of age-related regulation of genes', International Congress Series, vol. 1262, no. C, pp. 562-565. https://doi.org/10.1016/j.ics.2004.02.166
Kurachi, Kotoku ; Kurachi, Sumiko ; Zhang, Kezhong ; Ameri, Afshin ; Huo, Jeffrey ; Kuwahara, Mitsuhiro ; Fontaine, Jean Marc ; Abe, Takahiro. / Molecular mechanisms of age-related regulation of genes. In: International Congress Series. 2004 ; Vol. 1262, No. C. pp. 562-565.
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