Normal human lung fibroblasts were transfected with expression plasmids encoding mot-2, an hsp70 family member that is associated with the immortal phenotype. After the empty vector-transfected controls had become senescent and positive for senescence-associated beta-galactosidase (SA-beta-gal), the mot-2-expressing cells continued to proliferate for an additional 12-18 population doublings and showed a young cell morphology and much lower SA-beta-gal activity. The tumor suppressor p53 was found to be transcriptionally inactivated in life span-extended cells. We have thus shown for the first time that overexpression of mot-2 in normal human cells is able to permit their temporary escape from senescence.