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

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 molecula...

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Main Authors: Mari Yamagami, Motoyuki Otsuka, Takahiro Kishikawa, Kazuma Sekiba, Takahiro Seimiya, Eri Tanaka, Tatsunori Suzuki, Rei Ishibashi, Motoko Ohno, Kazuhiko Koike
Format: article
Language:EN
Published: Nature Portfolio 2018
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Online Access:https://doaj.org/article/85fad2daf73b4b2dacba3ae4e669a969
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Summary: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.