Fibroblasts from long‐lived Snell dwarf mice are resistant to oxygen‐induced in vitro growth arrest

Aging Cell - Tập 5 Số 1 - Trang 89-96 - 2006
Scott Maynard1, Richard A. Miller1
1Department of Pathology and Geriatrics Center, University of Michigan, and Ann Arbor VA Medical Center, Ann Arbor, MI 48109‐0940, USA

Tóm tắt

SummarySnell dwarf mice live longer than controls, and show lower age‐adjusted rates of lethal neoplastic diseases. Fibroblast cells from adult dwarf mice are resistant to the lethal effects of oxidative and nonoxidative stresses, including the carcinogen methyl methanesulfonate. We now report that dwarf‐derived fibroblasts are slow to enter the stage of growth arrest induced by culturing normal cells under standard culture conditions at 20% O2. Dwarf cells cultured at 20% O2 resemble control cells cultured at 3% O2 not only in their delayed growth arrest, but also in their rapid growth rates and resistance to both oxidative and nonoxidative forms of cytotoxic stress. Levels of the heat‐shock protein HSP‐70 respond to serum withdrawal and stress only in control cells, showing that intracellular signals are blunted in dwarf‐derived cells. These data suggest a model in which stable epigenetic changes induced in skin fibroblasts by the hormonal milieu of the Snell dwarf lead to resistance to multiple forms of injury, including the oxidative damage that contributes to growth arrest in vitro and neoplasia in intact mice.

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Tài liệu tham khảo

10.1023/A:1022448532248

10.1093/gerona/56.8.B340

10.1038/384033a0

10.1046/j.1474-9728.2003.00066.x

10.1210/en.2003-0374

10.1073/pnas.111158898

10.1038/nature01298

10.1093/gerona/58.4.B291

10.1002/j.1460-2075.1992.tb05433.x

10.1093/gerona/51A.6.B392

Karatza C, 1984, Kinetics of in vitro ageing of mouse embryo fibroblasts, J. Cell Sci., 65, 163, 10.1242/jcs.65.1.163

10.1016/S0031-9384(01)00423-1

10.1006/hbeh.2001.1654

10.1007/978-3-540-48003-7_7

10.1093/geronj/49.6.B270

Miller RA, 2001, Handbook of the Biology of Aging, 369

10.1128/MCB.17.9.5317

MurakamiS SalmonA MillerRA(2003a)Multiplex stress resistance in cells from long‐lived dwarf mice.FASEB Journalexpress article 10.1096/fj.02–1092fje. Published online 3 June 2003.

10.1096/fj.02-1092fje

10.1038/ncb1024

10.1152/ajpendo.00575.2004

Silberberg R, 1972, Articular aging and osteoarthritis in dwarf mice, Pathol. Microbiol. (Basel), 38, 417

10.1126/science.273.5271.63

10.1126/science.1081447

VergaraM Smith‐WheelockM HarperJM SiglerR MillerRA(2004) Hormone‐treated Snell dwarf mice regain fertility but remain long‐lived and disease resistant.J. Gerontol. Biol. Sci.59 1244–1250.

10.1016/S1534-5807(03)00323-X

10.1016/j.cell.2005.02.030

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Aging Cell

Tập 5 Số 1

89-96

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