Influences on the reduction of relative telomere length over 10 years in the population-based Bruneck Study: introduction of a well-controlled high-throughput assay

Abstract

This is the first comprehensive longitudinal study of individuals who were, on average, 60 at baseline, and who were re-evaluated 10 years later. Our methodology proved to be a reliable tool for a rapid, accurate and cost-efficient determination of RTL with a low amount of DNA.

Leukocyte Telomere Length and All-Cause, Cardiovascular Disease, and Cancer Mortality: Results From Individual-Participant-Data Meta-Analysis of 2 Large Prospective Cohort Studies

“…Whereas some earlier, relatively small studies had reported strong inverse association between LTL and mortality (17,41,42), much weaker associations or no association at all was seen in a number of larger, mostly more recent studies (11-13, 25, 26, 43). However, in the so far by far largest study from Denmark with 64,637 participants, with 7607 deaths during 22 years of follow-up, linear graded associations and modestly increased hazards for the shortest versus longest deciles of LTL were seen for all-cause mortality (HR: 1.40, 1.25-1.57), CVD mortality (1.36, 1.12-1.66) and cancer mortality (1.35, 1.11-1.65) (27).…”

Delayed paternal age of reproduction in humans is associated with longer telomeres across two generations of descendants

“…As cell replication generally requires a minimal TL, shortened TL is thought to contribute to senescence (6). Consistent with this, elderly persons with shorter telomeres (in blood) for their age have reduced survival (7)(8)(9)(10)(11)(12)(13).…”

“…To prevent gene loss, shortened telomeres generally activate damage response pathways that cause cell death or impairment of cellular function (2,3). Evidence that cell replication is limited by shorter TL has been reported in vitro (37)(38)(39)(40) through in vivo experimentation in animal models (41)(42)(43) and in cross-sectional and longitudinal observational studies (7)(8)(9)(10)(11)(12)(13)(44)(45)(46)(47)(48). On the other hand, whether inherited TL alters the risks of developing cancer is unsettled (20,21,(49)(50)(51)(52)(53), so the implications of the association of paternal ages at reproduction with TL for cancer risk are unclear.…”

“…Reactions were run with telomere primers (telg/telc) at 500 nM each and albumin (single-copy control) primers (albd/albu) at 300 nM each on a Bio-Rad iCycler iQ thermocycler with a modified thermo-profile: internal well factor collection for 1.5 min at 95°C; denaturation and Taq activation for 13.5 min at 95°C; two repeats of 2 s at 98°C followed by 30 s at 49°C; 34 repeats of 2 s at 98°C; 30 s at 59°C; 15 s at 74°C with signal acquisition; 30 s at 84°C; and 15 s at 85°C with signal acquisition, followed by a melt curve for PCR product verification. Data were analyzed with a per-well efficiency calculation method (7,67,68) using LinRegPCR version 12.7 (69,70). All telomere to single copy gene (T/S) ratios were normalized to (divided by) the same control sample run with six replicates per 96-well plate.…”

Telomeres and Lifestyle Choices

“…While cross-sectional studies are abundant, there have been very few longitudinal studies of telomere length [Aviv et al, 2009;Ehrlenbach et al, 2009;Epel et al, 2009;Nordfjall et al, 2009;Farzaneh-Far et al, 2010]. One consistent finding from the published longitudinal data is that the rate of telomere length change over time is inversely related to the baseline telomere length [Aviv et al, 2009;Farzaneh-Far et al, 2010].…”