Cells in the bone microenvironment exhibit increased senescent marker expression with age. Bones from young (6-month) and old (24-month) C57BL/6N male mice were isolated and processed to obtain cell suspensions for RNA analysis. qPCR revealed significant upregulation of p16Ink4a (a), p21cip (b), and p53 (c) mRNA expression in subsets of bone and marrow cell populations with age. For human studies, cells were isolated from needle bone biopsies taken from the posterior iliac crest of 10 young (mean ± SD; 27 ± 3 years) and 10 old (mean ± SD; 78 ± 6 years) healthy female volunteers. qPCR analysis indicated significant upregulation of p16Ink4a (d) and p21cip (e) with aging. OP = osteoprogenitors (Lin-Lepr+), OB = osteoblasts (AP+/CD31/34/45/54−), OCY = osteocytes (liberase-digested vertebrae), B = B cells (CD19+), T = T cells (CD3ε+), Myeloid = (CD14+). Data are presented as mean ± SE. *p < 0.05; **p < 0.01; ***p < 0.001; †p < 0.0001; ‡p < 0.00001 using two-sample t-test. Data are from Farr et al. (Farr et al., 2016)