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.
Abstract:
Senescent cell accumulation in aging tissues is linked to age-associated diseases and declining function, prompting efforts to eliminate them. Mass spectrometry analysis revealed that DPP4 (dipeptidyl peptidase 4) was selectively expressed on the surface of senescent, but not proliferating, human diploid fibroblasts. Importantly, the differential presence of DPP4 allowed flow cytometry-mediated isolation of senescent cells using anti-DPP4 antibodies. Moreover, antibody-dependent cell-mediated cytotoxicity (ADCC) assays revealed that the cell surface DPP4 preferentially sensitized senescent, but not dividing, fibroblasts to cytotoxicity by natural killer cells. In sum, the selective expression of DPP4 on the surface of senescent cells enables their preferential elimination.
Insights
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.
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.
