Mutations that extend nematode longevity by interference with IGF-I/insulin sensing pathways also lead to resistance to multiple forms of stress. Here, we report that skin-derived fibroblasts from Snell dwarf mice, already known to show increased longevity and delayed aspects of aging, are resistant to multiple forms of cellular stress, including UV light, heat, paraquat, H2O2, and the toxic metal cadmium. The findings suggest that increases in cellular resistance to stress may mediate extended longevity in mammals.