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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number2201409
JournalAdvanced Science
Volume9
Issue number25
DOIs
Publication statusPublished - Sep 5 2022

Keywords

  • aging
  • antiaging
  • hematopoietic stem cells (HSCs)
  • KLF1/EKLF
  • SUMOylation

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Materials Science(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Engineering(all)
  • Physics and Astronomy(all)

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