Methods We compared RTL in 510 sample pairs from the longitudinal population-based Bruneck Study, which were collected in 1995 and recollected in 2005, and additionally determined RTL from 159 participants who died during follow-up. RTL were determined by a high-throughput real-time PCR assay and by applying a mathematical model. Results The telomeres shortened, on average, by 455 bp over 10 years. The RTL shortening rate was highly correlated with baseline RTL (r ¼ 0.674, P < 0.001). Participants who died within the observed period had considerably shorter telomeres than those who survived (median RTL of 0.98 vs 1.49; P < 0.001). In contrast to previous studies, smoking behaviour had no influence on RTL and on telomere shortening. Conclusion 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.

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

Telomeres are nucleoprotein structures that cap the end of each chromosome arm and function to maintain genome stability. The length of telomeres is known to shorten with each cell division and it is well-established that telomere attrition is related to replicative capacity in vitro. Moreover, telomere loss is also correlated with the process of aging in vivo. In this review, we discuss the mechanisms that lead to telomere shortening and summarise telomere homeostasis in humans throughout a lifetime. In addition, we discuss the available evidence that shows that telomere shortening is related to human aging and the onset of age-related disease.

https://www.mdpi.com/2073-4409/8/1/73/pdf

Telomere Biology and Human Phenotype

Telomeres, repetitive DNA sequences found at the ends of linear chromosomes, play a role in regulat- ing cellular proliferation, and shorten with increasing age in proliferating human tissues. The rate of age-related shortening of telomeres is highest early in life and decreases with age. Shortened telomeres are thought to limit the proliferation of cells and are associated with increased morbidity and mortality. Although natural selection is widely assumed to operate against long telomeres because they entail increased cancer risk, the evidence for this is mixed. Instead, here it is proposed that telomere length is primarily limited by energetic constraints. Cell proliferation is ener- getically expensive, so shorter telomeres should lead to a thrifty phenotype. Shorter telomeres are proposed to restrain adaptive immunity as an energy saving mechanism. Such a limited immune system, however, might also result in chronic infections, inflammatory stress, premature aging, and death—a more ''disposable soma.'' With an increased reproductive lifespan, the fitness costs of premature aging are higher and longer telomeres will be favored by selection. Telomeres exhibit a paternal effect whereby the offspring of older fathers have longer telomeres due to increased telo- mere lengths of sperm with age. This paternal effect is proposed to be an adaptive signal of the expected age of male reproduction in the environment offspring are born into. The offspring of lineages of older fathers will tend to have lon- ger, and thereby less thrifty, telomeres, better preparing them for an environment with higher expected ages at repro- duction. Am. J. Hum. Biol. 23:149-167, 2011. ' 2010 Wiley-Liss, Inc.

https://faculty.washington.edu/dtae/manuscripts/Eisenberg%20-%20thrifty%20telomere%20-An%20evolutionary.pdf

An Evolutionary Review of Human Telomere Biology: The Thrifty Telomere Hypothesis and Notes on Potential Adaptive Paternal Effects

Although telomere length is genetically determined, mouse embryonic stem (ES) cells with telomeres of twice the normal size have been generated. Here, we use such ES cells with 'hyper-long' telomeres, which also express green fluorescent protein (GFP), to generate chimaeric mice containing cells with both hyper-long and normal telomeres. We show that chimaeric mice contain GFP-positive cells in all mouse tissues, display normal tissue histology and normal survival. Both hyper-long and normal telomeres shorten with age, but GFP-positive cells retain longer telomeres as mice age. Chimaeric mice with hyper-long telomeres also accumulate fewer cells with short telomeres and less DNA damage with age, and express lower levels of p53. In highly renewing compartments, such as the blood, cells with hyper-long telomeres are longitudinally maintained or enriched with age. We further show that wound-healing rates in the skin are increased in chimaeric mice. Our work demonstrates that mice with functional, longer and better preserved telomeres can be generated without the need for genetic manipulations, such as TERT overexpression.

/pdf/generation-of-mice-with-longer-and-better-preserved-4cf0lhhfy0.pdf

Generation of mice with longer and better preserved telomeres in the absence of genetic manipulations.

Placental telomere length decreases with gestational age and is influenced by parity: a study of third trimester live-born twins.

Haemopoietic stem cells (HSC) undergo a process of self renewal to constantly maintain blood cell turnover. However, it has become apparent that adult HSC lose their self-renewal ability with age. Telomere shortening in peripheral blood leukocytes has been seen to occur with age and it has been associated with loss of HSC proliferative capacity and cellular ageing. In contrast foetal HSC are known to have greater proliferative capacity than post-natal stem cells. However it is unknown whether they undergo a similar process of telomere shortening. In this study we show a more accentuated rate of telomere loss in leukocytes from pre term infants compared to human foetuses of comparable age followed longitudinally for 8-12 weeks in a longitudinal study. Our results point to a difference in HSC behaviour between foetal and early postnatal life which is independent of age but may be influenced by events at birth itself.

Rachel Chittick

Papers

Telomere length dynamics differ in foetal and early post-natal human leukocytes in a longitudinal study