2. Academic Validation
  3. The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice

The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice

  • Nat Metab. 2021 Dec;3(12):1706-1726. doi: 10.1038/s42255-021-00491-8.
Qixia Xu  # 1 2,  Qiang Fu  # 3,  Zi Li 4,  Hanxin Liu 3,  Ying Wang 1,  Xu Lin 4,  Ruikun He 5,  Xuguang Zhang 5,  Zhenyu Ju 6,  Judith Campisi 7 8,  James L Kirkland 9,  Yu Sun 10 11 12 13 14
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Tissue Microenvironment and Tumour, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 2 Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine & Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 3 Department of Pharmacology, Institute of Aging Medicine, Binzhou Medical University, Yantai, China.
  • 4 Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
  • 5 Science & Technology Centre, By-Health Corp. Ltd., Guangzhou, China.
  • 6 Key Laboratory of Regenerative Medicine of Ministry of Education, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, China.
  • 7 Buck Institute for Research on Aging, Novato, CA, USA.
  • 8 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
  • 9 Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
  • 10 CAS Key Laboratory of Tissue Microenvironment and Tumour, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. sunyu@sibs.ac.cn.
  • 11 Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine & Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. sunyu@sibs.ac.cn.
  • 12 Department of Pharmacology, Institute of Aging Medicine, Binzhou Medical University, Yantai, China. sunyu@sibs.ac.cn.
  • 13 Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China. sunyu@sibs.ac.cn.
  • 14 Department of Medicine and VAPSHCS, University of Washington, Seattle, WA, USA. sunyu@sibs.ac.cn.
  • # Contributed equally.
PMID: 34873338 DOI: 10.1038/s42255-021-00491-8
Abstract

Ageing-associated functional decline of organs and increased risk for age-related chronic pathologies is driven in part by the accumulation of senescent cells, which develop the senescence-associated secretory phenotype (SASP). Here we show that procyanidin C1 (PCC1), a polyphenolic component of grape seed extract (GSE), increases the healthspan and lifespan of mice through its action on senescent cells. By screening a library of Natural Products, we find that GSE, and PCC1 as one of its active components, have specific effects on senescent cells. At low concentrations, PCC1 appears to inhibit SASP formation, whereas it selectively kills senescent cells at higher concentrations, possibly by promoting production of Reactive Oxygen Species and mitochondrial dysfunction. In rodent models, PCC1 depletes senescent cells in a treatment-damaged tumour microenvironment and enhances therapeutic efficacy when co-administered with chemotherapy. Intermittent administration of PCC1 to either irradiated, senescent cell-implanted or naturally aged old mice alleviates physical dysfunction and prolongs survival. We identify PCC1 as a natural senotherapeutic agent with in vivo activity and high potential for further development as a clinical intervention to delay, alleviate or prevent age-related pathologies.

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