Longitudinal Changes in Leukocyte Telomere Length and Mortality in Humans

Bendix, Laila; Thinggaard, Mikael; Fenger, Mogens; Kølvraa, Steen; Avlund, Kirsten; Linneberg, Allan; Osler, Merete

doi:10.1093/gerona/glt153

Cited by 77 publications

(81 citation statements)

References 36 publications

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“…Most previous cross-sectional studies in which an association between smoking and short TL was reported were studies of female subjects only (11)(12)(13)(14)16), whereas those in which no association was reported were mostly studies of men or of older subjects (21,(23)(24)(25)(26), among whom estimates may be more likely to be biased because of higher rates of smoking cessation among older men with short TL. Previous longitudinal studies in which associations between smoking and TL attrition were reported involved younger subjects than did studies in which such an association was not reported (17)(18)(19)(20), further suggesting that estimates obtained from studies of older individuals could be biased because of adverse health-driven smoking cessation. In the Helsinki Businessmen Study, Strandberg et al (27) compared prospective and cross-sectional measures of smoking status and TL among men and reported findings consistent with those from our study.…”

Section: Discussionmentioning

confidence: 96%

“…However, epidemiologic reports of smoking and TL have been inconsistent; in some studies, investigators reported shorter TL associated with smoking (11)(12)(13)(14)(15)(16)(17)(18)(19)(20), whereas others found no association (21)(22)(23)(24)(25)(26). This inconsistency has also been seen in studies of smoking and longitudinal measures of TL attrition, with associations between smoking and TL shortening seen in some studies (17,18) but not in others (19,20). Furthermore, a study of older men in Finland (27) found that smoking during midlife was associated with short TL measured later in life but that smoking was not associated with TL in crosssectional analyses conducted in later life, which suggests that the timing of smoking behavior assessment may be important.…”

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confidence: 99%

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Sex-Specific and Time-Varying Associations Between Cigarette Smoking and Telomere Length Among Older Adults

Zhang¹,

Lauderdale²,

Pierce³

2016

Am. J. Epidemiol.

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Inconsistent associations between smoking and telomere length (TL) have been reported in epidemiologic studies, perhaps because of the time-varying nature of smoking behaviors. We estimated the associations of TL, which was measured by quantitative polymerase chain reaction using saliva DNA, with concurrent and past smoking status reported biennially for up to 16 years before TL measurement in 5,624 participants in the Health and Retirement Study (1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008). Smoking was associated with reduced TL when we used prospective data on smoking statuses among men and women, but the association was strongly attenuated among men in crosssectional analyses. This attenuation was largely due to a higher rate of smoking cessation during the study period among men with shorter TL than among men with longer TL. Short TL was also associated with poorer overall health in men, which suggests that male smokers with short TL were more likely to quit smoking because of poor health. Analyses of years since cessation, smoking duration, and pack-years of smoking all support the hypothesis that increased cigarette use shortens TL. Our results provide a potential explanation for the inconsistent associations between smoking and TL reported in previous cross-sectional studies. Time-varying associations should be considered in future studies of smoking behavior, TL, aging, and disease risk.aging; Health and Retirement Study; sex; smoking; smoking cessation; telomere length Abbreviations: HRS, Health and Retirement Study; TL, telomere length.Telomeres are DNA-protein complexes at chromosome ends that protect DNA from damage. Shortening of the DNA component of telomeres occurs with cell division, with average leukocyte telomere length (TL) decreasing by approximately 25 to 50 base pairs per year in adults (1). TL has been studied extensively as a biomarker of aging and susceptibility to age-related diseases, including cardiovascular diseases, cancers, and neurocognitive diseases (2-5).Cigarette smoking results in exposure to free radicals and reactive oxygen species, which leads to increased oxidative stress and inflammation (6). Both processes have also been linked to TL shortening (7-9), leading to the hypothesis that smoking promotes TL shortening (10). However, epidemiologic reports of smoking and TL have been inconsistent; in some studies, investigators reported shorter TL associated with smoking (11-20), whereas others found no association (21)(22)(23)(24)(25)(26). This inconsistency has also been seen in studies of smoking and longitudinal measures of TL attrition, with associations between smoking and TL shortening seen in some studies (17, 18) but not in others (19,20). Furthermore, a study of older men in Finland (27) found that smoking during midlife was associated with short TL measured later in life but that smoking was not associated with TL in crosssectional analyses conducted in later life, which suggests that the timing of smoking beh...

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Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

Sex-Specific and Time-Varying Associations Between Cigarette Smoking and Telomere Length Among Older Adults

Zhang¹,

Lauderdale²,

Pierce³

2016

Am. J. Epidemiol.

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“…However, more recent studies investigating cancer-specific associations have also correlated longer LTL with increased risk of certain malignancies, including pancreatic cancer, hepatocellular carcinoma, melanoma, sarcoma and lung adenocarcinoma (19)(20)(21)(22)(23)(24). With regards to all-cause mortality, several recent prospective cohort studies could not establish an association between LTL and all-cause mortality (12,25,26), while the by far largest study comprising a cohort of nearly 65.000 Danish individuals found linear graded associations of LTL with all-cause, CVD and cancer mortality (27).…”

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confidence: 99%

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

Mons

Müezzinler

Schöttker

et al. 2017

American Journal of Epidemiology

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“…Other recent meta-analyses support the concurrent associations between short telomeres and diabetes (8) and several cancers (9, 10). Several studies indicate that short telomeres from varied sources, including leukocytes and saliva, are related to early mortality (11-17), including a study with >60,000 adults (18), although null studies also exist (19)(20)(21)(22).Although these studies suggest that telomere length plays a role in disease, they are observational, and studies directly linking genetics of telomere length to disease would allow a more substantive inference of a causal role in disease pathogenesis. Recently, in humans, there were two such Mendelian randomization studies.…”

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confidence: 99%

mentioning

confidence: 99%

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study

Puterman

Gemmill

Karasek

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

148

108

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Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging. cellular aging | telomeres | lifespan adversity | childhood adversity A ging cells play a crucial role in the pathogenesis of noncommunicable diseases, and telomere shortening in cells plays a part of this aging process (1, 2). Telomeres are DNAprotein caps at the ends of chromosomes that protect genetic material from degradation, and their lengths indicate cellular aging (2, 3). Experiments in rodents implicate shortened telomeres and lower activity of telomerase, the enzyme that lengthens telomeres, as causes of mitochondrial and tissue damage associated with disease pathogenesis (4-6).Telomere length is linked cross-sectionally and prospectively with human disease states in many studies. A recent meta-analysis suggests that individuals with observed short leukocyte telomeres are at an ∼80% increased risk of concurrent reports of cardiovascular disease and an ∼40% increased risk of developing cardiovascular disease in the future (7). Other recent meta-analyses support the concurrent associations between short telomeres and diabetes (8) and several cancers (9, 10). Several studies indicate that short telomeres from varied sources, including leukocytes and saliva, are related to early mortality (11-17), including a study with >60,000 adults (18), although null studies also exist (19)(20)(21)(22).Although these studies suggest that telomere length plays a role in disease, they are observational, and studies directly linking genetics...

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Longitudinal Changes in Leukocyte Telomere Length and Mortality in Humans

Cited by 77 publications

References 36 publications

Sex-Specific and Time-Varying Associations Between Cigarette Smoking and Telomere Length Among Older Adults

Sex-Specific and Time-Varying Associations Between Cigarette Smoking and Telomere Length Among Older Adults

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

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study

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