日本东京大学Makoto Nakanishi研究团队近日取得一项新成果。经过不懈努力，他们发现抑制衰老细胞的谷氨酰胺分解可改善各种与年龄相关的疾病。相关论文发表在2021年1月15日出版的《科学》杂志上。

研究人员发现谷氨酰胺酶1（GLS1）是人类衰老细胞存活所必需的。破坏溶酶体膜降低了衰老细胞的胞内pH，并降低了pH诱导的肾型谷氨酰胺酶（KGA）表达。谷氨酰胺分解增强导致氨的产生，这中和了较低的pH并改善了衰老细胞的存活率。在老年小鼠中抑制KGA依赖性谷氨酰胺分解可以特异性消除衰老细胞并改善与年龄相关的器官功能障碍。

该研究结果表明，衰老细胞依赖谷氨酰胺分解，抑制其作用为体内诱导衰老提供了潜在策略。

据悉，已经研究表明去除衰老细胞有利于改善与年龄相关的疾病，但是维持衰老细胞活性的分子途径尚未揭示。

附：英文原文

Title: Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders

Author: 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

Issue&Volume: 2021/01/15

Abstract: 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.

DOI: 10.1126/science.abb5916

Source: https://science.sciencemag.org/content/371/6526/265