Tony Robertson

Gender and telomere length: Systematic review and meta-analysis

BACKGROUND It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. METHODS We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. RESULTS Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p=1.00) or cell type (p=0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. CONCLUSIONS Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required.

Is Socioeconomic Status Associated With Biological Aging as Measured by Telomere Length

It has been hypothesized that one way in which lower socioeconomic status (SES) affects health is by increasing the rate of biological aging. A widely used marker of biological aging is telomere length. Telomeres are structures at the ends of chromosomes that erode with increasing cell proliferation and genetic damage. We aimed to identify, through systematic review and meta-analysis, whether lower SES (greater deprivation) is associated with shorter telomeres. Thirty-one articles, including 29 study populations, were identified. We conducted 3 meta-analyses to compare the telomere lengths of persons of high and low SES with regard to contemporaneous SES (12 study populations from 10 individual articles), education (15 study populations from 14 articles), and childhood SES (2 study populations from 2 articles). For education, there was a significant difference in telomere length between persons of high and low SES in a random-effects model (standardized mean difference (SMD) = 0.060, 95% confidence interval (CI): 0.002, 0.118; P = 0.042), although a range of sensitivity analyses weakened this association. There was no evidence for an association between telomere length and contemporaneous SES (SMD = 0.104, 95% CI: −0.027, 0.236; P = 0.119) or childhood SES (SMD = −0.037, 95% CI: −0.143, 0.069; P = 0.491). These results suggest weak evidence for an association between SES (as measured by education) and biological aging (as measured by telomere length), although there was a lack of consistent findings across the SES measures investigated here.

Is Telomere Length a Biomarker for Aging: Cross-Sectional Evidence from the West of Scotland?

Background The search for biomarkers of aging (BoAs) has been largely unsuccessful to-date and there is widespread skepticism about the prospects of finding any that satisfy the criteria developed by the American Federation of Aging Research. This may be because the criteria are too strict or because a composite measure might be more appropriate. Telomere length has attracted a great deal of attention as a candidate BoA. We investigate whether it meets the criteria to be considered as a single biomarker of aging, and whether it makes a useful contribution to a composite measure. Methodology/Principal Findings Using data from a large population based study, we show that telomere length is associated with age, with several measures of physical and cognitive functioning that are related to normal aging, and with three measures of overall health. In the majority of cases, telomere length adds predictive power to that of age, although it was not nearly as good a predictor overall. We used principal components analysis to form two composites from the measures of functioning, one including telomere length and the other not including it. These composite BoAs were better predictors of the health outcomes than chronological age. There was little difference between the two composites. Conclusions Telomere length does not satisfy the strict criteria for a BoA, but does add predictive power to that of chronological age. Equivocal results from previous studies might be due to lack of power or the choice of measures examined together with a focus on single biomarkers. Composite biomarkers of aging have the potential to outperform age and should be considered for future research in this area.

Do symptoms of depression predict telomere length? Evidence from the west of Scotland twenty-07 study.

Objective Psychological factors such as the stress of caregiving are emerging as predictors of telomere length, an index of biological aging. However, although lifetime major depressive disorder is associated with shorter telomeres, less is known about depressive symptoms. Depression and depressive symptoms are associated with a range of morbidities and mortality, but the extent to which they predict biological aging is unclear. The present study examined participants in the West of Scotland Twenty-07 Study across three age cohorts and four waves of data collection from 1992/1993 to 2007/2008. Methods Participants were 37, 57, and 76 years old at final data collection. Depressive symptoms were measured using the Hospital Anxiety and Depression Scale at each time point. Telomere length was assessed from 1063 blood samples collected at the final wave in 2007/2008 for respondents who also had depression data. Results Average depression symptoms (&bgr;= −.12, p = .047) and their change over time (&bgr; = −.12, p = .031) were negatively associated with telomere length, but only in the youngest cohort. Depressive symptoms were not cross sectionally associated with telomere length in 2007 to 2008 (&bgr;= −.03, p = .45). In the youngest cohort only, depressive symptoms assessed in 1995 to 1997 and 2000 to 2004 were associated with shorter telomere length (&bgr; = .14 [p = .046] and &bgr; = .18 [p = .012], respectively), but not 1992 to 1993 or 2007 to 2008; associations in the middle- and older-aged cohorts were nonsignificant. Conclusions Depressive symptoms are longitudinally associated with shorter telomere length, but only in younger adults.

Telomere Attrition and Decreased Fetuin-A Levels Indicate Accelerated Biological Aging and Are Implicated in the Pathogenesis of Colorectal Cancer

Purpose: Increasing chronological age is a risk factor for many types of cancer including colorectal. An understanding of the biology of aging and factors which regulate it may provide insight into cancer pathogenesis. The role of telomere biology in both the cancer and aging process could prove useful in this regard. Experimental Design: Using quantitative PCR, we determined telomere length in the peripheral blood leukocytes of 64 colorectal cancer (CRC) patients and 1,348 controls. We also measured telomere length in 32 colorectal tumor samples and matched normal tissue. We aimed to assess whether telomere lengths were reflected in circulating mediators of inflammation and redox control factors, including fetuin-A, a circulating modulator of calcium homeostasis. Results: CRC patients had shorter telomeres [adjusted mean ratio of relative telomere repeat copy number to single-copy gene number (RelT/S) = 0.61] compared with chronologically older controls (mean age = 75, adjusted mean RelT/S = 0.70; ANCOVA, P = 0.004). Telomere length in tumor tissue [median = 0.43, interquartile range (IQR) = 0.40] was significantly shorter than adjacent normal tissue (median = 0.65, IQR = 0.28; P = 0.004). Patients with low fetuin-A levels were shown to have significantly shorter telomeres (P = 0.041). Patients with rectal tumors had significantly higher levels of fetuin-A than those with colonic tumors (P = 0.045). Conclusions: We have observed that patients with CRC display clear evidence of telomere attrition compared with controls. This is congruent with accelerated biological aging in the pathogenesis of CRC. An imbalance in redox control mechanisms and calcium homeostasis may be a contributing factor to telomere dynamics in our patients. Furthermore, fetuin-A levels can be used to distinguish between colon and rectal cancers. Clin Cancer Res; 17(17); 5573–81. ©2011 AACR.

Socioeconomic position across the lifecourse & allostatic load: data from the West of Scotland Twenty-07 cohort study

BackgroundWe examined how socioeconomic position (SEP) across the lifecourse (three critical periods, social mobility and accumulated over time) is associated with allostatic load (a measure of cumulative physiological burden).MethodsData are from the West of Scotland Twenty-07 Study, with respondents aged 35 (n = 740), 55 (n = 817) and 75 (n = 483). SEP measures representing childhood, the transition to adulthood and adulthood SEP were used. Allostatic load was produced by summing nine binary biomarker scores (1 = in the highest-risk quartile). Linear regressions were used for each of the lifecourse models; with model fits compared using partial F-tests.ResultsFor those aged 35 and 55, higher SEP was associated with lower allostatic load (no association in the 75-year-olds). The accumulation model (more time spent with higher SEP) had the best model fit in those aged 35 (b = −0.50, 95%CI = −0.68, −0.32, P = 0.002) and 55 (b = −0.31, 95%CI = −0.49, −0.12, P < 0.001). However, the relative contributions of each life-stage differed, with adulthood SEP less strongly associated with allostatic load.ConclusionsLong-term, accumulated higher SEP has been shown to be associated with lower allostatic load (less physiological burden). However, the transition to adulthood may represent a particularly sensitive period for SEP to impact on allostatic load.

Is Telomere Length Socially Patterned? Evidence from the West of Scotland Twenty-07 Study

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages.

The role of material, psychosocial and behavioral factors in mediating the association between socioeconomic position and allostatic load (measured by cardiovascular, metabolic and inflammatory markers).

Highlights • Lower socioeconomic position associated with higher cumulative physiological burden.• Material factors (home ownership and income) completely attenuated the association.• Psychological factors (as measured using GHQ-12) did not attenuate the association.• Smoking attenuated the association by approximately one third.• Alcohol, physical activity and diet had no attenuation impact.

Seven key investments for health equity across the lifecourse: Scotland versus the rest of the UK

While widespread lip service is given in the UK to the social determinants of health (SDoH), there are few published comparisons of how the UKs devolved jurisdictions ‘stack up’, in terms of implementing SDoH-based policies and programmes, to improve health equity over the life-course. Based on recent SDoH publications, seven key societal-level investments are suggested, across the life-course, for increasing health equity by socioeconomic position (SEP). We present hard-to-find comparable analyses of routinely collected data to gauge the relative extent to which these investments have been pursued and achieved expected goals in Scotland, as compared with England and Wales, in recent decades. Despite Scotlands longstanding explicit goal of reducing health inequalities, it has recently been doing slightly better than England and Wales on only one broad indicator of health-equity-related investments: childhood poverty. However, on the following indicators of other ‘best investments for health equity’, Scotland has not achieved demonstrably more equitable outcomes by SEP than the rest of the UK: infant mortality and teenage pregnancy rates; early childhood education implementation; standardised educational attainment after primary/secondary school; health care system access and performance; protection of the population from potentially hazardous patterns of food, drink and gambling use; unemployment. Although Scotland did not choose independence on September 18th, 2014, it could still (under the planned increased devolution of powers from Westminster) choose to increase investments in the underperforming categories of interventions for health equity listed above. However, such discussion is largely absent from the current post-referendum debate. Without further significant investments in such policies and programmes, Scotland is unlikely to achieve the ‘healthier, fairer society’ referred to in the current Scottish Governments official aspirations for the nation.

Allostatic load as a predictor of all-cause and cause-specific mortality in the general population: Evidence from the Scottish Health Survey

Allostatic load is a multiple biomarker measure of physiological ‘wear and tear’ that has shown some promise as marker of overall physiological health, but its power as a risk predictor for mortality and morbidity is less well known. This study has used data from the 2003 Scottish Health Survey (SHeS) (nationally representative sample of Scottish population) linked to mortality records to assess how well allostatic load predicts all-cause and cause-specific mortality. From the sample, data from 4,488 men and women were available with mortality status at 5 and 9.5 (rounded to 10) years after sampling in 2003. Cox proportional hazard models estimated the risk of death (all-cause and the five major causes of death in the population) according to allostatic load score. Multiple imputation was used to address missing values in the dataset. Analyses were also adjusted for potential confounders (sex, age and deprivation). There were 258 and 618 deaths over the 5-year and 10-year follow-up period, respectively. In the fully-adjusted model, higher allostatic load (poorer physiological ‘health’) was not associated with an increased risk of all-cause mortality after 5 years (HR = 1.07, 95% CI 0.94 to 1.22; p = 0.269), but it was after 10 years (HR = 1.08, 95% CI 1.01 to 1.16; p = 0.026). Allostatic load was not associated with specific causes of death over the same follow-up period. In conclusions, greater physiological wear and tear across multiple physiological systems, as measured by allostatic load, is associated with an increased risk of death, but may not be as useful as a predictor for specific causes of death.