第06讲 组织与细胞水平的衰老.ppt

* * mechanism of carcinogenesis * * 那么，既然p53P53是不是越多越好呢？ PNAS | October 16, 2007 | vol. 104 | no. 42 | 16633-16638 Declining p53 function in the aging process: A possible mechanism for the increased tumor incidence in older populations Zhaohui Feng*, Wenwei Hu*, Angelika K. Teresky*, Eva Hernando , Carlos Cordon-Cardo , and Arnold J. Levine*, Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903; Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY 10021; and School of Natural Sciences, Institute for Advanced Study, Princeton, NJ 08540 Decreased p53 responses to various stress signals in the cultured splenocytes isolated from aging mice. The splenocytes were isolated from 6-month-old and 21-month-old female C57BL/6 mice and exposed to various stress signals. (A–C) Cells were treated with IR (5 Gy) and collected at 6 h after IR. (A) ThemRNA levels were measured by real-time PCR. The gene induction fold was calculated as gene expression levels in irradiated cells compared with nonirradiated cells after normalization with actin. (B) The p53 protein levels were measured by ELISA. (C) Apoptotic cells were detected by Annexin V staining in a flow cytometer. (D–F) Splenocytes were isolated from 2-month-old p53/ or p53/ (D) and 6-month-old or 21-month-old (E and F) female wild-type C57BL/6 mice and exposed to etoposide (ETP, 10Mfor 10 h), adriamycin (ADR, 200 ng/ml for 24 h), ALLN (10 Mfor 12 h), actinomycin D (ACTD, 2 nM for 24 h), or Taxol (20 nM for 24 h). Apoptotic cells were detected by AnnexinVstaining in aflowcytometer (D and E), and the p53 protein levels were measured by ELISA (F). The p53 protein induction fold was calculated as the p53 levels in treated cells compared with untreated cells from the same mice. * * Figure 4 Phenotypes of aged p53+/+ and p53+/m mice. a, Photograph of a 24-month-old p53+/+ male mouse. b, Photograph of a 24-month-old p53+/m male mouse showing red