Positive correlation between mammalian life span and cellular resistance to stress

Identifying the mechanisms determining species-specific life spans is a cen tral challenge in understanding the biology of aging. Cellular stresses pro duce damage, that may accumulate and cause aging. Evolution theory predicts that long-lived species secure their longevity through investment in a mor e durable soma, including enhanced cellular resistance to stress. To invest igate whether cells from long-lived species have better mechanisms to cope with oxidative and non-oxidative stress, we compared cellular resistance of primary skin fibroblasts from eight mammalian species with a range of life spans. Cell survival was measured by the thymidine incorporation assay fol lowing stresses induced by paraquat, hydrogen peroxide, tert-butyl hydroper oxide, sodium arsenite and alkaline pH (sodium hydroxide). Significant posi tive correlations between cell LD90 and maximum life span were found for al l these stresses. Similar results were obtained when cell survival was meas ured by the MTT assay, and when lymphocytes from different species were com pared. Cellular resistance to a variety of oxidative and non-oxidative stre sses was positively correlated with mammalian longevity. Our results suppor t the concept that the gene network regulating the cellular response to str ess is functionally important in aging and longevity. (C) 1999 Elsevier Sci ence Inc.