Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders

doi:10.1126/science.abb5916

GSTDTAP > 气候变化

DOI	10.1126/science.abb5916
	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. Nakayama; Yoichi Furukawa; Seiya Imoto; Makoto Nakanishi
	2021-01-15
发表期刊	Science
出版年	2021
英文摘要	Senescent cells are associated with a variety of age-related medical conditions and thus have been proposed as potential targets for therapy, but we do not yet have a full understanding of the underlying mechanisms. Johmura et al. used RNA interference to screen for enzymes essential to the survival of senescent cells (see the Perspective by Pan and Locasale). The authors identified a key role for glutamine metabolism, particularly the enzyme glutaminase 1, and demonstrated that inhibition of this pathway induced the death of senescent cells. Glutaminase targeting also ameliorated aging-related organ dysfunction and obesity-related disorders in mouse models, suggesting the potential therapeutic value of this approach. Science , this issue p. [265][1]; see also p. [234][2] 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. [1]: /lookup/doi/10.1126/science.abb5916 [2]: /lookup/doi/10.1126/science.abf6368
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/311498
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Yoshikazu Johmura,Takehiro Yamanaka,Satotaka Omori,et al. Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders[J]. Science,2021.
APA	Yoshikazu Johmura.,Takehiro Yamanaka.,Satotaka Omori.,Teh-Wei Wang.,Yuki Sugiura.,...&Makoto Nakanishi.(2021).Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders.Science.
MLA	Yoshikazu Johmura,et al."Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders".Science (2021).