Telomere length predicts replicative capacity of human fibroblasts

Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10114-8. doi: 10.1073/pnas.89.21.10114.

Abstract

When human fibroblasts from different donors are grown in vitro, only a small fraction of the variation in their finite replicative capacity is explained by the chronological age of the donor. Because we had previously shown that telomeres, the terminal guanine-rich sequences of chromosomes, shorten throughout the life-span of cultured cells, we wished to determine whether variation in initial telomere length would account for the unexplained variation in replicative capacity. Analysis of cells from 31 donors (aged 0-93 yr) indicated relatively weak correlations between proliferative ability and donor age (m = -0.2 doubling per yr; r = -0.42; P = 0.02) and between telomeric DNA and donor age (m = -15 base pairs per yr; r = -0.43; P = 0.02). However, there was a striking correlation, valid over the entire age range of the donors, between replicative capacity and initial telomere length (m = 10 doublings per kilobase pair; r = 0.76; P = 0.004), indicating that cell strains with shorter telomeres underwent significantly fewer doublings than those with longer telomeres. These observations suggest that telomere length is a biomarker of somatic cell aging in humans and are consistent with a causal role for telomere loss in this process. We also found that fibroblasts from Hutchinson-Gilford progeria donors had short telomeres, consistent with their reduced division potential in vitro. In contrast, telomeres from sperm DNA did not decrease with age of the donor, suggesting that a mechanism for maintaining telomere length, such as telomerase expression, may be active in germ-line tissue.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cell Division*
  • Cells, Cultured
  • DNA / genetics
  • DNA / isolation & purification
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Humans
  • Male
  • Progeria / pathology
  • Progeria / physiopathology
  • Reference Values
  • Repetitive Sequences, Nucleic Acid
  • Skin / cytology
  • Skin Aging / physiology*
  • Skin Physiological Phenomena
  • Spermatozoa / physiology*
  • Telomere / physiology*
  • Telomere / ultrastructure

Substances

  • DNA