Is Telomere Length a Biomarker of Aging? A Review

Mather, Karen A.; Jorm, Anthony F; Parslow, Ruth; Christensen, Helen

doi:10.1093/gerona/glq180

Cited by 375 publications

(303 citation statements)

References 101 publications

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“…Third, we tested 2 indicators of accelerated aging. Although some commentators have questioned whether TL is an appropriate biomarker of aging, 36 we confirmed a previous report that shorter TL is associated with older perceived age in the expected direction. 8 We used a perinatal complication index that was previously shown to predict cognitive problems in the Dunedin Study at ages 3, 5, 7, 11, and 13 years.…”

Section: Discussionsupporting

confidence: 89%

Perinatal Complications and Aging Indicators by Midlife

2014

PEDIATRICS

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WHAT'S KNOWN ON THIS SUBJECT: Perinatal complications predict increased risk for morbidity and early mortality. Evidence of perinatal programming of adult mortality raises the question of what mechanisms embed this long-term effect. Telomere length and perceived facial age are 2 indicators of accelerated aging. WHAT THIS STUDY ADDS:Perinatal complications predicted greater signs of accelerated aging "inside," as measured objectively by leukocyte telomere length, an indicator of cellular aging, and "outside," as measured subjectively by perceived age, an indicator of declining integrity of tissues. abstract BACKGROUND: Perinatal complications predict increased risk for morbidity and early mortality. Evidence of perinatal programming of adult mortality raises the question of what mechanisms embed this long-term effect. We tested a hypothesis related to the theory of developmental origins of health and disease: that perinatal complications assessed at birth predict indicators of accelerated aging by midlife.METHODS: Perinatal complications, including both maternal and neonatal complications, were assessed in the Dunedin Multidisciplinary Health and Development Study cohort (N = 1037), a 38-year, prospective longitudinal study of a representative birth cohort. Two aging indicators were assessed at age 38 years, objectively by leukocyte telomere length (TL) and subjectively by perceived facial age. RESULTS:Perinatal complications predicted both leukocyte TL (b = 20.101; 95% confidence interval, 20.169 to 20.033; P = .004) and perceived age (b = 0.097; 95% confidence interval, 0.029 to 0.165; P = .005) by midlife. We repeated analyses with controls for measures of family history and social risk that could predispose to perinatal complications and accelerated aging, and for measures of poor health taken in between birth and the age-38 follow-up. These covariates attenuated, but did not fully explain the associations observed between perinatal complications and aging indicators.CONCLUSIONS: Our findings provide support for early-life developmental programming by linking newborns' perinatal complications to accelerated aging at midlife. We observed indications of accelerated aging "inside," as measured by leukocyte TL, an indicator of cellular aging, and "outside," as measured by perceived age, an indicator of declining tissue integrity. A better understanding of mechanisms underlying perinatal programming of adult aging is needed. Pediatrics 2014;134:e1315-e1323 AUTHORS:

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Section: Discussionsupporting

confidence: 89%

Perinatal Complications and Aging Indicators by Midlife

2014

PEDIATRICS

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“…Thus, our findings may not apply to other cell types or tissues in the body or to acutely or severely ill inpatients with the illness. Another limitation of this, and other published studies of LTL in schizophrenia, is the use of a crosssectional design, which makes assessments of telomere trajectory or rate of telomere shortening in individual subjects impossible (Mather et al, 2011). Unless all trajectories of LTL with age parallel each other, the trajectory of LTL with age in cross-sectional studies does not well indicate the individual trajectories for subjects in the population (Kraemer et al, 2000;Louis et al, 1986;Vollmer, 1993).…”

Section: Discussionmentioning

confidence: 96%

“…Due to relatively high inter-individual variability in LTL at any time point, clearer interpretations are possible only from examining intra-individual, rather than between-individual or betweengroup, patterns longitudinally (Mather et al, 2011). Such studies should always include an HC group, separate analyses of men and women, adequate sample sizes within each group, consideration of possible differences in the aging process in each group (gender and diagnosis), and careful consideration of other covariates either interacting with, or collinear with gender, age, or diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…Accelerated biological aging occurs when biological age outpaces chronological age (Lindqvist et al, 2015). One marker of biological age is telomere length (TL), often measured in leukocytes (LTL), since it progressively declines with age and may be inversely related to diseases of aging and mortality (Bojesen, 2013;Cawthon et al, 2003;Mather et al, 2011;Muezzinler et al, 2013;Svensson et al, 2014). However, peak LTL (shortly after birth), the age at which a decline begins, the rate of decline, and when death interrupts the process, vary among individuals (Svensson et al, 2014), suggesting important interindividual differences in the rates of biological aging (Epel, 2012;Lindqvist et al, 2015;Muezzinler et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Leukocyte telomere length: Effects of schizophrenia, age, and gender

Wolkowitz

Jeste

Martin

et al. 2017

Journal of Psychiatric Research

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a b s t r a c tBackground: Schizophrenia is linked with early medical comorbidity and mortality. These observations indicate possible "accelerated biological aging" in schizophrenia, although prior findings are mixed, and few such studies have examined the role of gender. One putative marker of biological aging is leukocyte telomere length (LTL), which typically shortens with age. Methods: We assessed LTL in phenotypically well characterized 134 individuals with schizophrenia (60 women and 74 men) and 123 healthy comparison subjects (HCs) (66 women and 57 men), aged 26 to 65 years. Results: Overall, LTL was inversely associated with age (t(249) ¼ -6.2, p < 0.001), and a gender effect on the rate of LTL decrease with age was found (t(249) ¼ 2.20, p ¼ 0.029), with men declining more rapidly than women. No significant overall effect of diagnosis on the rate of decline was detected. However, at the average sample age (48 years), there was a significant gender effect in both schizophrenia and HC groups (t(249) ¼ 2.48, p ¼ 0.014), with women having longer LTL than men, and a significant gender X diagnosis effect (t(249) ¼ 2.43, p ¼ 0.016) -at the average sample age, women with schizophrenia had shorter LTL than HC women. Discussion: Gender, not the diagnosis of schizophrenia, was the major factor involved with LTL shortening across the age range studied. We discuss the constraints of a cross-sectional design and other methodological issues, and indicate future directions. Understanding the impact of schizophrenia on biological aging will require separate evaluations in men and women.Published by Elsevier Ltd.

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“…Telomere maintenance has relevance for long-term health. Shortened telomere length and/or reduced telomerase activity have been consistently associated with health risk and diseases (12)(13)(14)(15). Declines in the telomere/telomerase maintenance system may play a causal role in aging, serve as a biomarker of aging, or both.…”

Section: Developmental Programming | Fetal Originmentioning

confidence: 99%

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

Entringer

Epel

Kumsta

et al. 2011

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

349

244

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Leukocyte telomere length (LTL) is a predictor of age-related disease onset and mortality. The association in adults of psychosocial stress or stress biomarkers with LTL suggests telomere biology may represent a possible underlying mechanism linking stress and health outcomes. It is, however, unknown whether stress exposure in intrauterine life can produce variations in LTL, thereby potentially setting up a long-term trajectory for disease susceptibility. We, therefore, as a first step, tested the hypothesis that stress exposure during intrauterine life is associated with shorter telomeres in adult life after accounting for the effects of other factors on LTL. LTL was assessed in 94 healthy young adults. Forty-five subjects were offspring of mothers who had experienced a severe stressor in the index pregnancy (prenatal stress group; PSG), and 49 subjects were offspring of mothers who had a healthy, uneventful index pregnancy (comparison group; CG). Prenatal stress exposure was a significant predictor of subsequent adult telomere length in the offspring (178-bp difference between prenatal stress and CG; d = 0.41 SD units; P < 0.05). The effect was substantially unchanged after adjusting for potential confounders (subject characteristics, birth weight percentile, and early-life and concurrent stress level), and was more pronounced in women (295-bp difference; d = 0.68 SD units; P < 0.01). To the best of our knowledge, this study provides the first evidence in humans of an association between prenatal stress exposure and subsequent shorter telomere length. This observation may help shed light on an important biological pathway underlying the developmental origins of adult health and disease risk.developmental programming | fetal origin

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Is Telomere Length a Biomarker of Aging? A Review

Cited by 375 publications

References 101 publications

Perinatal Complications and Aging Indicators by Midlife

Perinatal Complications and Aging Indicators by Midlife

Leukocyte telomere length: Effects of schizophrenia, age, and gender

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

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