A Multiparametric Assay to Evaluate Senescent Cells
Cellular senescence is a permanent growth arrest mechanism triggered by various forms of stress. Senescent cells accumulate in the mammalian organism with age and are present at sites of tissue damage and age related pathologies. However, the characterization of senescence cells in vivo is currently limited and the need for new technologies to detect and monitor the senescence state in vivo has greatly increased. Here we demonstrate the use of the ImageStreamX as a powerful method for detection and quantification of senescent cells at distinct tissues and cell subpopulations. The identification of senescent cells using ImageStreamX enables the use of a combination of several senescence-related markers, together with the commonly used senescence-associated beta-galactosidase assay. These can be combined with the use of other molecular features typical of senescence cells, such as the γH2AX foci, indicating the activation of DNA damage response. This novel method offers a feasible solution to quantify senescent cells in vivo, in a comprehensive manner. Such quantification is necessary in order to understand the role of cellular senescence in aging and disease.
Key wordsCellular senescence ImageStreamX SA-β-Gal Aging DNA damage response
This work was supported by grants to V.K. from the European Research Council under the European Union’s FP7 and from the Israel Science Foundation; and staff scientist internal grant from the Weizmann Institute of Science to Z.P. V.K. is an incumbent of the Karl and Frances Korn Career Development Chair in Life Sciences.
- 1.Campisi J (2013) Aging, cellular senescence, and cancer. Annu Rev Physiol 75:685–705. https://doi.org/10.1146/annurev-physiol-030212-183653CrossRefGoogle Scholar
- 12.Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, Peacocke M, Campisi J (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92:9363–9367CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Davalos AR, Kawahara M, Malhotra GK, Schaum N, Huang J, Ved U, Beausejour CM, Coppe JP, Rodier F, Campisi J (2013) p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes. J Cell Biol 201:613–629. https://doi.org/10.1083/jcb.201206006CrossRefPubMedPubMedCentralGoogle Scholar