2. Academic Validation
  3. PKM2 aggregation drives metabolism reprograming during aging process

PKM2 aggregation drives metabolism reprograming during aging process

  • Nat Commun. 2024 Jul 9;15(1):5761. doi: 10.1038/s41467-024-50242-y.
Juntao Bie # 1 2,  Ridong Li # 3,  Yutong Li 1,  Chen Song 1,  Zhaoming Chen 4,  Tianzhuo Zhang 5,  Zhiheng Tang 6,  Li Su 7,  Liangyi Zhu 8,  Jiaxin Wang 9,  You Wan 9 10,  Jun Chen 11,  Xiaoyun Liu 12 13,  Tingting Li 14 15,  Jianyuan Luo 16 17 18
Affiliations

Affiliations

  • 1 Department of Medical Genetics, Center for Medical Genetics, Peking University Health Science Center, Beijing, 100191, China.
  • 2 Medical Innovation Center (Taizhou) of Peking University, Taizhou, 225316, China.
  • 3 Institute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
  • 4 Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
  • 5 Department of Anesthesiology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, 100142, China.
  • 6 Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
  • 7 Peking university medical and health analysis center, Beijing, 100191, China.
  • 8 Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing, 100191, China.
  • 9 Neuroscience Research Institute, Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
  • 10 Key Laboratory for Neuroscience, Ministry of Education/National Health Commission of China, Peking University, Beijing, 100191, China.
  • 11 Peking University Research Center on Aging, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Biophysics, School of Basic Medical Science, Peking University, Beijing, 100191, China. cjbiochem@bjmu.edu.cn.
  • 12 Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. xiaoyun.liu@bjmu.edu.cn.
  • 13 NHC Key Laboratory of Medical Immunology, Peking University, Beijing, 100191, China. xiaoyun.liu@bjmu.edu.cn.
  • 14 Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. litt@hsc.pku.edu.cn.
  • 15 Key Laboratory for Neuroscience, Ministry of Education/National Health Commission of China, Peking University, Beijing, 100191, China. litt@hsc.pku.edu.cn.
  • 16 Department of Medical Genetics, Center for Medical Genetics, Peking University Health Science Center, Beijing, 100191, China. luojianyuan@bjmu.edu.cn.
  • 17 Medical Innovation Center (Taizhou) of Peking University, Taizhou, 225316, China. luojianyuan@bjmu.edu.cn.
  • 18 Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. luojianyuan@bjmu.edu.cn.
  • # Contributed equally.
PMID: 38982055 DOI: 10.1038/s41467-024-50242-y
Abstract

While protein aggregation's association with aging and age-related diseases is well-established, the specific proteins involved and whether dissolving them could alleviate aging remain unclear. Our research addresses this gap by uncovering the role of PKM2 aggregates in aging. We find that PKM2 forms aggregates in senescent cells and organs from aged mice, impairing its enzymatic activity and glycolytic flux, thereby driving cells into senescence. Through a rigorous two-step small molecule library screening, we identify two compounds, K35 and its analog K27, capable of dissolving PKM2 aggregates and alleviating senescence. Further experiments show that treatment with K35 and K27 not only alleviate aging-associated signatures but also extend the lifespan of naturally and prematurely aged mice. These findings provide compelling evidence for the involvement of PKM2 aggregates in inducing cellular senescence and aging phenotypes, and suggest that targeting these aggregates could be a promising strategy for Anti-aging drug discovery.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z