The senescence of mammalian cells is characterized by a proliferative arrest in response to stress and the expression of an inflammatory phenotype. Chromatin modifications have been implicated in the stable repression of proliferative genes in senescence, and in the derepression of inflammatory genes. We used mass spectrometry to characterize the chromatin of senescent cells (Contrepois et al. J. Proteome Res., 2010 and Contrepois et al. Epigenetics & Chromatin, 2012). We discovered that H2A.J, a poorly studied H2A variant found only in mammals, accumulates in human fibroblasts in senescence with persistent DNA damage. H2A.J also accumulates in mice with aging in a tissue-specific manner. Knock-down of H2A.J inhibited the derepression of inflammatory genes that contribute to the senescent-associated secretory phenotype (SASP), and over-expression of H2A.J increased the expression of some of these genes in proliferating cells. H2A.J accumulation may thus promote the signaling of senescent cells to the immune system, and it may contribute to chronic inflammation and the development of diseases with aging. We are currently investigating the mechanism by which H2A.J promotes inflammatory gene expression in senescent cells, and we are interested in studying its functions in tissues in which H2A.J accumulation does not appear to be linked to senescence.