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Related Concept Videos

Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

770
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
770

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Far-Red Fluorescent Senescence-Associated &#946;-Galactosidase Probe for Identification and Enrichment of Senescent Tumor Cells by Flow Cytometry
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Identification of senescent cell surface targetable protein DPP4.

Kyoung Mi Kim1, Ji Heon Noh1, Monica Bodogai1

  • 1National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.

Genes & Development
|September 8, 2017
PubMed
Summary

Researchers identified dipeptidyl peptidase 4 (DPP4) on senescent cells. Targeting DPP4 offers a promising strategy for selectively eliminating these cells to combat aging and disease.

Keywords:
CD26cell senescencehuman diploid fibroblasts

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Area of Science:

  • Cellular senescence
  • Immunology
  • Biochemistry

Background:

  • Accumulation of senescent cells in aging tissues contributes to age-related diseases and functional decline.
  • Targeting senescent cells is a therapeutic strategy to improve healthspan.

Purpose of the Study:

  • To identify cell surface markers for selective elimination of senescent cells.
  • To investigate the role of DPP4 in senescent cell biology.

Main Methods:

  • Mass spectrometry was used to analyze protein expression on senescent and proliferating fibroblasts.
  • Flow cytometry with anti-DPP4 antibodies was employed for cell isolation.
  • Antibody-dependent cell-mediated cytotoxicity (ADCC) assays assessed NK cell activity.

Main Results:

  • Dipeptidyl peptidase 4 (DPP4) was selectively expressed on the surface of senescent human diploid fibroblasts, but not proliferating ones.
  • Anti-DPP4 antibodies enabled flow cytometry-based isolation of senescent cells.
  • Cell surface DPP4 sensitized senescent cells to natural killer cell-mediated cytotoxicity via ADCC.

Conclusions:

  • DPP4 is a selective surface marker for senescent cells.
  • Targeting cell surface DPP4 facilitates the preferential elimination of senescent cells.
  • This finding provides a novel strategy for senolytic therapies.