Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders

Yoshikazu Johmura, Takehiro Yamanaka, Satotaka Omori, Teh Wei Wang, Yuki Sugiura, Masaki Matsumoto, Narumi Suzuki, Soichiro Kumamoto, Kiyoshi Yamaguchi, Seira Hatakeyama, Tomoyo Takami, Rui Yamaguchi, Eigo Shimizu, Kazutaka Ikeda, Nobuyuki Okahashi, Ryuta Mikawa, Makoto Suematsu, Makoto Arita, Masataka Sugimoto, Keiichi I. NakayamaYoichi Furukawa, Seiya Imoto, Makoto Nakanishi

研究成果: Article査読

59 被引用数 (Scopus)

抄録

Removal of senescent cells (senolysis) has been proposed to be beneficial for improving age-associated pathologies, but the molecular pathways for such senolytic activity have not yet emerged. Here, we identified glutaminase 1 (GLS1) as an essential gene for the survival of human senescent cells. The intracellular pH in senescent cells was lowered by lysosomal membrane damage, and this lowered pH induced kidney-type glutaminase (KGA) expression. The resulting enhanced glutaminolysis induced ammonia production, which neutralized the lower pH and improved survival of the senescent cells. Inhibition of KGA-dependent glutaminolysis in aged mice eliminated senescent cells specifically and ameliorated age-associated organ dysfunction. Our results suggest that senescent cells rely on glutaminolysis, and its inhibition offers a promising strategy for inducing senolysis in vivo.

本文言語English
ページ(範囲)265-270
ページ数6
ジャーナルScience
371
6526
DOI
出版ステータスPublished - 2021 1月 15

ASJC Scopus subject areas

  • 一般

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