Telomeric length and telomerase activity vary with age in peripheral blood cells obtained from normal individuals

Abstract

The telomerase activity and length of telomeres of peripheral blood mononuclear cells obtained from 124 healthy individuals aged 4-95 years was measured. Telomerase activity level was semiquantitatively assessed by a fluorescent-telomeric repeat amplification protocol (fluorescent-TRAP) using an internal telomerase assay standard, fluorescent primers and an automated laser fluorescent DNA sequencer. Telomeric length, measured by assay of terminal restriction fragments (TRFs), was determined in HinfI-digested DNA by Southern blot analysis using a (TTAGGG)4 probe. TRF length was determined in 80 individuals and age-related progressive reduction of size was observed. TRF length in peripheral blood mononuclear cells obtained from normal individuals (aged 4-39 years) decreased by approximately 84 bp per year, while in individuals aged > or = 40 years it decreased by 41 bp per year. In contrast, telomerase activity showed an apparent biphasic pattern with aging. Individuals aged 4-39 years showed a progressive decrease in telomerase activity, whereas 65% of those aged > or = 40 years showed relatively stable but very low telomerase activity, and the remaining individuals aged > or = 40 years had no detectable telomerase activity. These data obtained from normal individuals might in the future be of value to help risk stratify and manage the care of patients with leukemia.

Lineage-Specific Telomere Shortening and Unaltered Capacity for Telomerase Expression in Human T and B Lymphocytes with Age

“…Telomerase activity was undetected in the majority of donor CD4 ϩ (75%) and CD8 ϩ (83%) T cells and B (91%) cell populations. Low levels of telomerase activity were detected in some donors and did not appear to be restricted to the young donors as previously reported (18) or to either gender (Fig. 2).…”

“…Age influence on telomerase activity in PBMC has been reported recently (18). It was found that telomerase activity in freshly isolated PBMC markedly declined from newborn to adolescence and was stable at low to undetectable levels in all adult life (18). Because PBMC consist of multiple cell lineages, such differences in telomerase activity may reflect changes such as decreased numbers of telomeraseexpressing stem cells and naive T cells newly derived from the thymus.…”

“…In contrast, lymphocytes appear to regulate telomerase activity through mechanisms other than the quantitative level of hTERT mRNA (35). Age influence on telomerase activity in PBMC has been reported recently (18). It was found that telomerase activity in freshly isolated PBMC markedly declined from newborn to adolescence and was stable at low to undetectable levels in all adult life (18).…”

“…Telomere shortening with age has been reported in human peripheral blood leukocytes (16,17), in PBMC (18), and in T cells (19,20). The rate of telomere shortening appears not to be uniform throughout life.…”

“…Loss of telomeres was reported to be most rapid from newborn to 4 years of age, with that rate gradually declining between age 4 and 39 years, and with telomere shortening continuing at a relatively stable and low rate between age 40 and 95 years (17,20). Telomerase activity in PBMC also varied with age and was detectable in many newborns and in some children before adolescence, decreasing to low or undetectable levels after age 20 (18). In addition, lymphocytes are capable of expressing induced telomerase activity after antigenic activation both in vivo (21,22) and in vitro (23)(24)(25), in what appears to be a specifically regulated process.…”