論文

査読有り 国際誌
2015年4月29日

Ablation of the p16(INK4a) tumour suppressor reverses ageing phenotypes of klotho mice.

Nature communications
  • Seidai Sato
  • ,
  • Yuka Kawamata
  • ,
  • Akiko Takahashi
  • ,
  • Yoshinori Imai
  • ,
  • Aki Hanyu
  • ,
  • Atsushi Okuma
  • ,
  • Masaki Takasugi
  • ,
  • Kimi Yamakoshi
  • ,
  • Hiroyuki Sorimachi
  • ,
  • Hiroaki Kanda
  • ,
  • Yuichi Ishikawa
  • ,
  • Saburo Sone
  • ,
  • Yasuhiko Nishioka
  • ,
  • Naoko Ohtani
  • ,
  • Eiji Hara

6
開始ページ
7035
終了ページ
7035
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/ncomms8035

The p16(INK4a) tumour suppressor has an established role in the implementation of cellular senescence in stem/progenitor cells, which is thought to contribute to organismal ageing. However, since p16(INK4a) knockout mice die prematurely from cancer, whether p16(INK4a) reduces longevity remains unclear. Here we show that, in mutant mice homozygous for a hypomorphic allele of the α-klotho ageing-suppressor gene (kl(kl/kl)), accelerated ageing phenotypes are rescued by p16(INK4a) ablation. Surprisingly, this is due to the restoration of α-klotho expression in kl(kl/kl) mice and does not occur when p16(INK4a) is ablated in α-klotho knockout mice (kl(-/-)), suggesting that p16(INK4a) is an upstream regulator of α-klotho expression. Indeed, p16(INK4a) represses α-klotho promoter activity by blocking the functions of E2Fs. These results, together with the observation that the expression levels of p16(INK4a) are inversely correlated with those of α-klotho throughout ageing, indicate that p16(INK4a) plays a previously unrecognized role in downregulating α-klotho expression during ageing.

リンク情報
DOI
https://doi.org/10.1038/ncomms8035
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25923845
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421814
ID情報
  • DOI : 10.1038/ncomms8035
  • PubMed ID : 25923845
  • PubMed Central 記事ID : PMC4421814

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