title: Telomere length predicts replicative capacity of human fibroblasts.
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.
authors.affiliation: Department of Biochemistry, McMaster University, Hamilton, ON, Canada.
authors.forename: R C
authors.initials: RC
authors.lastname: Allsopp
authors.forename: H
authors.initials: H
authors.lastname: Vaziri
authors.forename: C
authors.initials: C
authors.lastname: Patterson
authors.forename: S
authors.initials: S
authors.lastname: Goldstein
authors.forename: E V
authors.initials: EV
authors.lastname: Younglai
authors.forename: A B
authors.initials: AB
authors.lastname: Futcher
authors.forename: C W
authors.initials: CW
authors.lastname: Greider
authors.forename: C B
authors.initials: CB
authors.lastname: Harley
mesh_terms: D001483:Base Sequence; D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D008297:Male; D011371:Progeria / Q000473:pathology / Q000503:physiopathology; D012016:Reference Values; D012091:Repetitive Sequences, Nucleic Acid; D012867:Skin / Q000166:cytology; D015595:Skin Aging / Q000502:physiology*; D012879:Skin Physiological Phenomena; D013094:Spermatozoa / Q000502:physiology*; D016615:Telomere / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D004247:DNA