This project is based on the general hypothesis that the mechanism of cellular senescence is, in part at least, dependent on altered gene expression. We have prepared RNA stocks from young and senescent cells at seven time points. We have worked extensively with the G0 time point (i.e. unstimulated cells) and identified by screening eleven genes that are differentially expressed. We plan now to characterize four of these extensively. Two of them, EPC-1 and EPC-A2 are overexpressed in young cells; LPC-1 is overexpressed in senescent cells and its expression is uncoupled from the cell cycle. The fourth is the mitochondrial electron transport system genes. These are overexpressed in senescent cells. We plan to characterize the regulation and physiologic significance of altered regulation of these genes. In addition, we will compare the alterations resulting from aging in vitro with possible changes in early passage skin fibroblasts from people of different ages. Finally, as time permits, we will identify and characterize additional differentially expressed genes.
| Francis, Mary Kay; Appel, Stacia; Meyer, Christine et al. (2004) Loss of EPC-1/PEDF expression during skin aging in vivo. J Invest Dermatol 122:1096-105 |
| Pignolo, Robert J; Francis, Mary Kay; Rotenberg, Mitch O et al. (2003) Putative role for EPC-1/PEDF in the G0 growth arrest of human diploid fibroblasts. J Cell Physiol 195:12-20 |
| Cristofalo, Vincent J; Beck, Jeanne; Allen, R G (2003) Cell senescence: an evaluation of replicative senescence in culture as a model for cell aging in situ. J Gerontol A Biol Sci Med Sci 58:B776-9; discussion 779-81 |
| Torres, Claudio; Francis, Mary Kay; Lorenzini, Antonello et al. (2003) Metabolic stabilization of MAP kinase phosphatase-2 in senescence of human fibroblasts. Exp Cell Res 290:195-206 |
| Gerhard, Glenn S; Benko, Floyd A; Allen, R G et al. (2002) Mitochondrial DNA mutation analysis in human skin fibroblasts from fetal, young, and old donors. Mech Ageing Dev 123:155-66 |
| Mawal-Dewan, Madhu; Lorenzini, Antonello; Frisoni, Lorenza et al. (2002) Regulation of collagenase expression during replicative senescence in human fibroblasts by Akt-forkhead signaling. J Biol Chem 277:7857-64 |
| Macera-Bloch, Lisa; Houghton, JeanMarie; Lenahan, Melanie et al. (2002) Termination of lifespan of SV40-transformed human fibroblasts in crisis is due to apoptosis. J Cell Physiol 190:332-44 |
| Lorenzini, Antonello; Tresini, Maria; Mawal-Dewan, Madhu et al. (2002) Role of the Raf/MEK/ERK and the PI3K/Akt(PKB) pathways in fibroblast senescence. Exp Gerontol 37:1149-56 |
| Tresini, M; Lorenzini, A; Frisoni, L et al. (2001) Lack of Elk-1 phosphorylation and dysregulation of the extracellular regulated kinase signaling pathway in senescent human fibroblast. Exp Cell Res 269:287-300 |
| Lorenzini, A; Hrelia, S; Bordoni, A et al. (2001) Is increased arachidonic acid release a cause or a consequence of replicative senescence? Exp Gerontol 36:65-78 |
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