npj Aging and Mechanisms of Disease (Nov 2018)

ISGF3 with reduced phosphorylation is associated with constitutive expression of interferon-induced genes in aging cells

  • Mari Yamagami,
  • Motoyuki Otsuka,
  • Takahiro Kishikawa,
  • Kazuma Sekiba,
  • Takahiro Seimiya,
  • Eri Tanaka,
  • Tatsunori Suzuki,
  • Rei Ishibashi,
  • Motoko Ohno,
  • Kazuhiko Koike

DOI
https://doi.org/10.1038/s41514-018-0030-6
Journal volume & issue
Vol. 4, no. 1
pp. 1 – 10

Abstract

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Aging and inflammation: aging cells express interferon-stimulated genes in a non-canonical pathway Aging cells express many kinds of inflammation-related genes called SASP (senescence-associated secretary-phenotype), which are involved in aging-associated phenotypes. However, the underlying molecular mechanisms how such inflammatory gene expression is induced in aging cells are unclear. A team led by Motoyuki Otsuka at the University of Tokyo found that using senescent human fibroblasts interferon-stimulated genes do not express in a canonical interferon-related intracellular signaling pathway. Normally, interferon-stimulated genes are expressed through the phosphorylation of STAT proteins triggered by interferon stimulation. In contrast, in senescent cells, interferon-stimulated genes were highly expressed without interferon stimulation and the representative STAT phosphorylation was not induced. These findings indicate that the interferon-stimulated genes in aging cells are expressed in a mechanism different from a canonical interferon-related pathway. Further research into these phenomena may develop a way to intervene the senescence-associated phenotypes in aging.