Leukocyte Telomere Length in Newborns: Implications for the Role of Telomeres in Human Disease

Factor-Litvak, Pam; Süsser, Ezra; Kezios, Katrina; McKeague, Ian W.; Kark, Jeremy D.; Hoffman, Matthew; Kimura, Masayuki; Wapner, Ronald J.; Aviv, Abraham

doi:10.1542/peds.2015-3927

Cited by 193 publications

(212 citation statements)

References 47 publications

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“…Moreover, genetic analyses have revealed that alleles associated with short LTL are also associated with CVD [10–12], largely excluding the possibility of reverse causality, i.e., CVD causing LTL shortening. Coupled with observations that LTL, which reflects telomere length in somatic tissues [13], is highly heritable [14,15] and is largely determined at birth [16], these findings suggest that telomere length might play an active role in CVD and longevity. Such a conclusion is relevant to the debate about the existence of a natural lifespan limit for humans [17–21].…”

Section: Introductionmentioning

confidence: 65%

Telomeres and the natural lifespan limit in humans

Steenstrup

Kark

Verhulst

et al. 2017

Aging

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An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics during adult life could set a maximal natural lifespan limit. We define leukocyte telomere length of 5 kb as the ‘telomeric brink’, which denotes a high risk of imminent death. We show that a subset of adults may reach the telomeric brink within the current life expectancy and more so for a 100-year life expectancy. Thus, secular trends in life expectancy should confront a biological limit due to crossing the telomeric brink.

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Section: Introductionmentioning

confidence: 65%

Telomeres and the natural lifespan limit in humans

Steenstrup

Kark

Verhulst

et al. 2017

Aging

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“…TL, which is a highly heritable complex genetic trait [25–27], displays wide variation across the population, a phenomenon that is already observed at birth [28]. While individuals with constitutively long telomeres are prone to major cancers [7–14], those with constitutively short telomeres are prone to atherosclerotic cardiovascular disease [29–31], perhaps the most common human degenerative disease.…”

Section: Evolutionary and Epidemiological Perspectivesmentioning

confidence: 99%

Mutations, Cancer and the Telomere Length Paradox

2017

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Individuals with short telomeres should be at increased risk for cancer, since short telomeres lead to genomic instability— a hallmark of cancer. However, individuals with long telomeres also display an increased risk for major cancers, thus creating a cancer-telomere length paradox. The two-stage clonal expansion model we propose is based on the thesis that a series of mutational hits (1st Hit) at the stem-cell level generates a clone with replicative advantage. A series of additional mutational hits (2nd Hit) transforms the expanding clone into cancer. By proposing that the 1st Hit is largely telomere length-independent, while the 2nd Hit is largely telomere length-dependent, we resolve the paradox, highlighting a regulatory role of telomeres in cancer.

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“…Aging starts even before birth, that is why is necessary not only to study telomere length at birth, as a prerequisite to understand its dynamics throughout life, but also to investigate several exposures, and genetic and epigenetic factors that may contribute to accelerate this process [37]. Aging is defined as the time-dependent event that results in a progressive functional decline that affects most living organisms.…”

Section: Telomere Length and Human Healthmentioning

confidence: 99%

Telomere Length and Its Relation to Human Health

Kahl¹,

Silva²

2016

Telomere - A Complex End of a Chromosome

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Telomeres are complex nucleotide sequences that cap the end of chromosomes from degradation, unwanted recombination-fusion, inappropriate activation of DNA damage response and play a critical role in cell division and chromosome stability. There is growing evidence that telomere stability can be affected by occupational and environmental exposure, as some of these factors have been correlated with increase in inflammation, oxidative stress, DNA damage, chromosome aberration, and epigenetic alterations. Both extremely short and long telomeres have been associated with neurodegenerative, cardiovascular diseases (CVD) and cancer risk. Occupational and environmental exposure to several synthetic and natural chemicals has been found to be associated with changes in telomere length, although the molecular mechanism is not fully understood. Telomeric DNA is relatively less capable of repair, resulting in accelerated shortening during the cell cycle and replicative senescence. It is recognized that diet plays an important role in telomere maintenance. Prevention of exposure to environmental and occupational hazards as well as psychological stressors can reduce the risk of telomere instability. This review provides a broad evaluation of the associated mechanism between human health and environmental and occupational exposure with telomere length, including recent findings and future perspectives.

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Leukocyte Telomere Length in Newborns: Implications for the Role of Telomeres in Human Disease

Cited by 193 publications

References 47 publications

Telomeres and the natural lifespan limit in humans

Telomeres and the natural lifespan limit in humans

Mutations, Cancer and the Telomere Length Paradox

Telomere Length and Its Relation to Human Health

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