Mild stress-induced hormesis is an effective strategy to intervene in the aging process. Repeated exposure of human skin fibroblasts to 41 degrees C heat shock for 1 h twice a week is an example of mild stress that has many hormetic effects, including improved resistance to other stressors. We are now developing an experimental model system of sugar-induced premature senescence, which can be useful to test the hormetic and antiaging effects of other stresses. Our present studies show that early-passage human skin fibroblasts treated with 1 mM glyoxal for 72 h undergo premature senescence in terms of enlarged cell size, inhibition of cell division, slowing down of cell growth, a decrease in the number of DNA synthesizing cells, and increased resistance to apoptosis.