Genetic Disruption of KLF1 K74 SUMOylation in Hematopoietic System Promotes Healthy Longevity in Mice

Yu Chiau Shyu, Po Cheng Liao, Ting Shou Huang, Chun Ju Yang, Mu Jie Lu, Shih Ming Huang, Xin Yu Lin, Cai Cin Liou, Yu Hsiang Kao, Chi Huan Lu, Hui Ling Peng, Jim Ray Chen, Wen Jin Cherng, Ning I. Yang, Yung Chang Chen, Heng Chih Pan, Si Tse Jiang, Chih Chin Hsu, Gigin Lin, Shin Sheng YuanPaul Wei Che Hsu, Kou Juey Wu, Tung Liang Lee, Che Kun James Shen

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)


The quest for rejuvenation and prolonged lifespan through transfusion of young blood has been studied for decades with the hope of unlocking the mystery of the key substance(s) that exists in the circulating blood of juvenile organisms. However, a pivotal mediator has yet been identified. Here, atypical findings are presented that are observed in a knockin mouse model carrying a lysine to arginine substitution at residue 74 of Krüppel-like factor 1 (KLF1/EKLF), the SUMOylation-deficient Klf1K74R/K74R mouse, that displayed significant improvement in geriatric disorders and lifespan extension. Klf1K74R/K74R mice exhibit a marked delay in age-related physical performance decline and disease progression as evidenced by physiological and pathological examinations. Furthermore, the KLF1(K74R) knockin affects a subset of lymphoid lineage cells; the abundance of tumor infiltrating effector CD8+ T cells and NKT cells is increased resulting in antitumor immune enhancement in response to tumor cell administration. Significantly, infusion of hematopoietic stem cells (HSCs) from Klf1K74R/K74R mice extends the lifespan of the wild-type mice. The Klf1K74R/K74R mice appear to be an ideal animal model system for further understanding of the molecular/cellular basis of aging and development of new strategies for antiaging and prevention/treatment of age-related diseases thus extending the healthspan as well as lifespan.

期刊Advanced Science
出版狀態已發佈 - 9月 5 2022

ASJC Scopus subject areas

  • 醫藥(雜項)
  • 化學工程 (全部)
  • 材料科學(全部)
  • 生物化學、遺傳與分子生物學(雜項)
  • 工程 (全部)
  • 物理與天文學 (全部)


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