Abstract
Senescence is a permanent growth arrest that restricts the lifespan of primary cells in culture, and represents an in vitro model for aging. Senescence functions as a tumor suppressor mechanism that can be induced independent of replicative crisis by diverse stress stimuli. RNase-L mediates antiproliferative activities and functions as a tumor suppressor in prostate cancer, therefore, we examined a role for RNase-L in cellular senescence and aging. Ectopic expression of RNase-L induced a senescent morphology, a decrease in DNA synthesis, an increase in senescence-associated beta-galactosidase activity, and accelerated replicative senescence. In contrast, senescence was retarded in RNase-L-null fibroblasts compared with wild-type fibroblasts. Activation of endogenous RNase-L by 2-5A transfection induced distinct senescent and apoptotic responses in parental and Simian virus 40-transformed WI38 fibroblasts, respectively, demonstrating cell type specific differences in the antiproliferative response to RNase-L activation. Replicative senescence is a model for in vivo aging; therefore, genetic disruption of senescence effectors may impact lifespan. RNase-L-/- mice survived 31.7% (P
| Original language | English |
|---|---|
| Journal | Oncogene |
| Volume | 26 |
| Issue number | 21 |
| Pages (from-to) | 3081-8 |
| Number of pages | 8 |
| ISSN | 0950-9232 |
| DOIs | |
| Publication status | Published - 10 May 2007 |
| Externally published | Yes |
Keywords
- Aging
- Animals
- BALB 3T3 Cells
- Cell Aging
- Cell Line, Transformed
- Cells, Cultured
- Endoribonucleases
- Longevity
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Knockout
- Tumor Suppressor Proteins
