Identification of senescent cell surface targetable protein DPP4

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 di...

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Published in:Genes & development Vol. 31; no. 15; p. 1529
Main Authors: Kim, Kyoung Mi, Noh, Ji Heon, Bodogai, Monica, Martindale, Jennifer L, Yang, Xiaoling, Indig, Fred E, Basu, Sandip K, Ohnuma, Kei, Morimoto, Chikao, Johnson, Peter F, Biragyn, Arya, Abdelmohsen, Kotb, Gorospe, Myriam
Format: Journal Article
Language:English
Published: United States 01.08.2017
Subjects:
Adult
Aged
Aged, 80 and over
Antibody-Dependent Cell Cytotoxicity
Cells, Cultured
Cellular Senescence - physiology
Cyclin-Dependent Kinase Inhibitor p16 - genetics
Dipeptidyl Peptidase 4 - metabolism
Diploidy
Fibroblasts - metabolism
Flow Cytometry
Humans
Killer Cells, Natural - metabolism
Lymphocyte Subsets - enzymology
Mass Spectrometry
Membrane Proteins - metabolism
RNA, Messenger - metabolism
RNA, Ribosomal - metabolism
human diploid fibroblasts
CD26
cell senescence
ISSN:1549-5477, 1549-5477
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Summary: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.
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ISSN:1549-5477
1549-5477
DOI:10.1101/gad.302570.117