The rate of telomere sequence loss in human leukocytes varies with age

Abstract

A gradual loss of telomeric repeat sequences with aging previously has been noted in normal adult tissues, and this process has been implicated in cell senescence. No data exist that address the rate of telomere shortening in normal human cells within families or early in life. To address these questions, we measured telomere lengths in peripheral blood leukocytes (PBLs) from 75 members of 12 families and in a group of unrelated healthy children who were 5-48 months old. Here we report the surprising observation that rates of telomere attrition vary markedly at different ages. Telomeric repeats are lost rapidly (at a rate of >1 kilobase per year) from the PBLs of young children, followed by an apparent plateau between age 4 and young adulthood, and by gradual attrition later in life. These data suggest that the loss of telomeric repeats in hematopoietic cells is a dynamic process that is differentially regulated in young children and adults. Our results have implications for current models of how telomeric sequences are lost in normal somatic cells and suggest that PBLs are an excellent tissue to investigate how this process is controlled.

Figure 1

Telomere repeats in a multigenerational family. Leukocyte DNA was digested with BglII and hybridized with a probe that recognizes the TTAGGG telomeric repeat. Lanes 1–5 contain DNA from umbilical cord of a newborn infant (1), his mother (2), father (3), maternal grandmother (4), and maternal grandfather (5). The wider vertical length in the bands seen in lanes 2–5 reflect greater variability in the length in individual telomeres in the leukocyte populations of adults relative to neonatal PBLs (lane 1).

Figure 2

Telomere lengths in 10 unrelated children between ages 5 and 24 months. ▪ shows the mean ± 1 SD for neonatal specimens. The R value of the regression line is 0.65, and the coefficient of variance (R²) is 0.424.

Figure 3

Phases of telomere shortening in normal PBLs. The point shown for age 5 is taken from the oldest child shown in Fig. 2. The initial phase is characterized by rapid loss of telomeric repeats. An apparent stabilization then occurs between age 5 and young adulthood. Telomere loss resumes at a slower rate later as adults grow older. See text for further discussion.