2. Academic Validation
  3. Combining adoptive NK cell infusion with a dopamine-releasing peptide reduces senescent cells in aged mice

Combining adoptive NK cell infusion with a dopamine-releasing peptide reduces senescent cells in aged mice

  • Cell Death Dis. 2022 Apr 5;13(4):305. doi: 10.1038/s41419-022-04562-w.
Zongke Bai  # 1 2,  Peiwei Yang  # 1 2,  Fan Yu 1 2,  Zhong Li 3,  Zheng Yao 1 2,  Jean Martinez 4,  Mengwei Li 1 2,  Hanmei Xu 5 6
Affiliations

Affiliations

  • 1 The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation, Jiangsu Province, China Pharmaceutical University, Nanjing, 210009, P.R. China.
  • 2 State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, P.R. China.
  • 3 Shanghai Engineering Research Center for Cell Therapy, Shanghai, 201805, China.
  • 4 Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
  • 5 The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation, Jiangsu Province, China Pharmaceutical University, Nanjing, 210009, P.R. China. xuhanmei6688@126.com.
  • 6 State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, P.R. China. xuhanmei6688@126.com.
  • # Contributed equally.
PMID: 35383143 DOI: 10.1038/s41419-022-04562-w
Abstract

Aging inducing the development of senescent cells (SNCs) in various tissues is considered as the main cause of the age-related diseases. Senotherapy has become a promising Anti-aging therapy. However, the effectivity and side-effect of senolytic agents are still concern. Here, we observed the downregulation of senescence-related genes by adoptive infusion of natural killer (NK) cells in 26 cases in peripheral blood CD3+ T cells. NK cell treatment also significantly decreased levels of senescence markers and senescence-associated secretory phenotypes (SASPs) in three senescent adipose tissues when culturing them together. Interestingly, cytotoxic activity of mouse NK cells against SNCs was significantly enhanced by dopamine in vitro through D1-like receptors. Acein, dopamine-releasing peptide, promoted the adoptive infusion of NK cells in effectively eliminating SNCs in a variety of tissues and reduced local and systemic SASPs in aging mice but Acein alone did not have the senolytic effect. These data demonstrated that adoptive infusion of NK cells is an effective means in removing SNCs, and peptide Acein combined with NK cells further enhances this effect in aging mice.

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