Extension of Life-Span by Introduction of Telomerase into Normal Human Cells

TLDR

Normal human cells undergo a finite number of divisions before entering replicative senescence, a process thought to be driven by telomere shortening. The study aimed to test whether introducing telomerase into telomerase‑negative retinal pigment epithelial cells and foreskin fibroblasts would prevent senescence. The authors transfected the cells with vectors encoding the human telomerase catalytic subunit. Telomerase expression elongated telomeres, allowed continued vigorous division, reduced senescence markers, preserved normal karyotype, and extended the cells’ life‑span by at least 20 doublings, demonstrating a causal link between telomere shortening and senescence and suggesting useful applications.

Abstract

Normal human cells undergo a finite number of cell divisions and ultimately enter a nondividing state called replicative senescence. It has been proposed that telomere shortening is the molecular clock that triggers senescence. To test this hypothesis, two telomerase-negative normal human cell types, retinal pigment epithelial cells and foreskin fibroblasts, were transfected with vectors encoding the human telomerase catalytic subunit. In contrast to telomerase-negative control clones, which exhibited telomere shortening and senescence, telomerase-expressing clones had elongated telomeres, divided vigorously, and showed reduced staining for β-galactosidase, a biomarker for senescence. Notably, the telomerase-expressing clones have a normal karyotype and have already exceeded their normal life-span by at least 20 doublings, thus establishing a causal relationship between telomere shortening and in vitro cellular senescence. The ability to maintain normal human cells in a phenotypically youthful state could have important applications in research and medicine.