The senescence phenotype is heterogeneous, as observed by the context-dependent differential expression of senescence markers. Here, we provide evidence to demonstrate an inverse relationship in the expression pattern of the two murine variants of p21 (p21v1, and p21v2) in aging and hemorrhagic shock. While an upregulation of p21v1 was observed following hemorrhagic shock injury, p21v2 was upregulated in the aged mouse. We further show that the p21v1 response is, at least, partially independent of p53.