EXTENSION OF LIFE-SPAN BY INTRODUCTION OF TELOMERASE INTO NORMAL HUMAN-CELLS

Normal human cells undergo a finite number of cell divisions and ultim ately enter a nondividing state called replicative senescence. It has been proposed that telomere shortening is the molecular clock that tri ggers senescence, To test this hypothesis, two telomerase-negative nor mal human cell types, retinal pigment epithelial cells and foreskin fi broblasts, were transfected with vectors encoding the human telomerase catalytic subunit. In contrast to telomerase-negative control clones, which exhibited telomere shortening and senescence, telomerase-expres sing clones had elongated telomeres, divided vigorously, and showed re duced staining for beta-galactosidase, a biomarker for senescence, Not ably, the telomerase-expressing clones have a normal karyotype and hav e already exceeded their normal life-span by at least 20 doublings, th us establishing a causal relationship between telomere shortening and in vitro cellular senescence. The ability to maintain normal human cel ls in a phenotypically youthful state could have important application s in research and medicine.