Childhood Growth, IQ and Education as Predictors of
White Blood Cell Telomere Length at Age 49–51 Years:
The Newcastle Thousand Families Study
Mark S. Pearce1*, Kay D. Mann1, Carmen Martin-Ruiz2, Louise Parker3, Martin White1, Thomas von
Zglinicki2, Jean Adams1
1Institute of Health & Society, Newcastle University, Newcastle Upon Tyne, England, United Kingdom, 2Institute for Ageing and Health, Newcastle University, Newcastle
Upon Tyne, England, United Kingdom, 3Departments of Medicine and Paediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
Background: Telomere length is emerging as a potential factor in the pathogenesis of cardiovascular disease. We
investigated whether birth weight, infant growth, childhood cognition and adult height, as well as a range of lifestyle, socio-
economic and educational factors, were associated with white blood cell telomere length at age 49–51 years.
Methods: The study included 318 members of the Newcastle Thousand Families Study, a prospectively followed birth
cohort which includes all individuals born in Newcastle, England in May and June 1947, who attended for clinical
examination at age 49–51 years, and had telomere length successfully measured using real-time PCR analyses of DNA
extracted from peripheral blood mononuclear cells.
Results: No association was found between birth weight and later telomere length. However, associations were seen with
other factors from early life. Education level was the only predictor in males, while telomere length in females was
associated with gestational age at birth, childhood growth and childhood IQ.
Conclusions: While these findings may be due to chance, in particular where differing associations were seen between
males and females, they do provide evidence of early life associations with telomere length much later in life. Our findings
of sex differences in the education association may reflect the sex differences in achieved education levels in this generation
where few women went to university regardless of their intelligence. Our findings do not support the concept of telomere
length being on the pathway between very early growth and later disease risk.
Citation: Pearce MS, Mann KD, Martin-Ruiz C, Parker L, White M, et al. (2012) Childhood Growth, IQ and Education as Predictors of White Blood Cell Telomere
Length at Age 49–51 Years: The Newcastle Thousand Families Study. PLoS ONE 7(7): e40116. doi:10.1371/journal.pone.0040116
Editor: Fre ´de ´rique Magdinier, INSERM UMR S_910, France
Received February 7, 2012; Accepted June 1, 2012; Published July 6, 2012
Copyright: ? 2012 Pearce et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was partly supported by funding from the Faculty of Public Health Medicine/BUPA research fellowship (2001–4) awarded to JA and by a
Research into Aging programme grant awarded to TvZ. JA is funded in full and MW in part by Fuse - the Centre for Translational Research in Public Health, a UK
Clinical Research Collaboration (UKCRC) Public Health Research Centre of Excellence. Funding for Fuse is provided by the British Heart Foundation, Cancer
Research UK, Economic and Social Research Council, Medical Research Council, and National Institute of Health Research. The views expressed in this paper do not
necessarily represent those of the funders or UKCRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: email@example.com
Telomere length has been reported to be associated with
longevity and risk of a number of age-related diseases, including
associations with cardiovascular disease [1–3], type 2 diabetes
mellitus , vascular  and Alzheimer’s dementia [6–7] and
solid tissue tumours . However, it has been suggested that the
associations with morbidity and mortality are not apparent in very
old age .
Risk of adverse health in middle age has been proposed to be
‘programmed’ by impaired development in utero . Early
growth has also been linked to physical functioning on older age
. Telomere length is known to vary at birth  and has been
suggested to be a biological marker on the pathway between early
growth and later health . Further, it has been associated with
age-related mortality and morbidity . Low birth weight children
may have shorter telomeres in childhood , although very low
birth weight newborns were found to have longer telomeres in
cord blood than low birth weight newborns . However, when
comparing small-for-gestational-age newborns to appropriately
grown controls, telomere lengths were shown to be similar .
Associations between early growth and telomere length in later life
do not appear to have been studied previously.
A recent study has suggested a link between education and
telomere length in adulthood . However, in addition to
studying whether early growth or education are associated with a
later outcome such as telomere length, it is also important to
address whether factors later in life such as smoking, diet, physical
activity and alcohol consumption, may have a more important role
in influencing telomere length. It is only by studying detailed
PLoS ONE | www.plosone.org1July 2012 | Volume 7 | Issue 7 | e40116
longitudinal birth cohort data in an appropriate manner, that
questions regarding relative contributions and mediating pathways
can be addressed.
The Newcastle Thousand Families birth cohort  provides
such an opportunity to investigate the determinants of telomere
length at age 49–51 years from across the life course and their
relative contribution to explaining variation in telomere length. A
previous investigation of the telomere data for this cohort found
that telomere length was longer in men than in women , but
did not find associations with socio-economic status or a number
of lifestyle factors. The current study investigated the potential
associations and interactions between sex and a number of
markers of body size at different stages of life, including achieved
adult height, childhood cognition, education and further adult
lifestyle factors and peripheral blood telomere length at age 49–51
years in members of the Newcastle Thousand Families birth
The study received ethical approval from the South Durham
Lead Research Ethics Committee and the Joint Newcastle Health
Authority/University of Newcastle upon Tyne Ethics Committee,
and all study members gave their written informed consent.
The Newcastle Thousand Families study began as a prospective
study of all 1142 children born in May and June 1947 to mothers
resident in Newcastle upon Tyne, UK . The health, growth
and development of the cohort were followed in great detail up to
age 15. Throughout the first years of the children’s lives, all
families were visited both on a routine (up to every six weeks
during infancy and at least quarterly until age five years) and on an
ad hoc basis by the study team, which consisted of health visitors
(nurses who visited families at home) and paediatricians.
The cohort underwent a major follow-up at age 49–51 years
. Participants were members of the cohort who were either
traced through the National Health Service Central Register or
contacted the study team in response to media publicity. Between
October 1996 and December 1998, health and lifestyle question-
naires were sent out for completion and return and study members
were invited to attend for clinical examination which took place
over the same time period.
Between October 1996 and December 1998, when study
members were aged between 49 and 51 years, height, weight and
other markers of size were measured. Waist and hip circumfer-
ences were measured according to the protocol of the World
Health Organisation Monitoring Trends and Determinants in
Cardiovascular Disease project . Percent body fat was
estimated from impedance measured using a Holtain body
composition analyser (Holtain Ltd, Crymych, Wales, UK).
Telomere length in peripheral blood mononuclear cells was
measured using real-time polymerase chain reaction (PCR)
analysis  on DNA extracted from blood donated at age 49–
51 years with the following modifications: Measurements were
performed in quadruplicate. All PCRs were carried out on an
Applied Biosystems 7900HT Fast Real Time PCR machine with
384-well plate capacity. For T/S ratios, the coefficients of
variation (CV) were 4.5% (intra-assay) and 6.2% (inter-assay),
respectively. In addition, four internal control DNA samples were
run within each plate to correct for plate–to-plate variation. This
enabled the calculation of absolute telomere length (in kb) from the
T/S ratios and further reduced the inter-assay CV to below 5%.
The reproducibility of the whole technique including DNA
isolation had also been tested in the same laboratory using parallel
but independent blood samples , resulting in a CV of 2%.
Measurement of Size and Growth in Early Life
Birth weights, as recorded by the midwife, were standardised for
gestational age (as recorded in ante-natal records) and sex .
Growth in early childhood was defined as the standard deviation
(z) score for height at age nine years, the age in childhood for
which the most complete data were available, less the z-score for
weight at birth. Childhood BMI, also measured at this age was also
included in analyses. Liaison with schools enabled the prospective
collection of information on educational performance. In 1958,
study members took the 11-plus examination, consisting of written
papers involving tests of verbal reasoning (Moray House tests 57
and 58) and two standardized tests of English and arithmetical
ability. The total IQ score was derived as the average of the four
test results. At that time in England, the 11-plus examination was a
standard test used in educational establishments at the age of 11
years, often to determine the type of secondary school at which a
child was to continue their education. Results of 11-plus
examinations were not available for those children who had
moved away from the study area.
Measurement of Adult Lifestyle
The number of pack-years of cigarettes smoked, current
smoking status, physical activity, alcohol consumption and
achieved education level were derived from the responses to
the self-completion questionnaire data at age 49–51 years .
Four categories of alcohol consumption were derived: No
drinking; light drinking (up to ten units/week of alcohol for
males, 5 units for females); moderate drinking (11–28 units for
males, 6–21 units for females) and heavy drinking (.28 units for
males, .21 units for females). In the UK, one unit is 10 ml or
8 g of pure alcohol. The number of pack-years of cigarettes
smoked (one pack-year = one pack of cigarettes smoked per day
for one year) was estimated from the study members’ smoking
habits at ages 15, 25, 35 and 50, as ascertained at age 49–51
years. Current smoking status (at the time of questionnaire
completion) was also derived (never, ex-smoker, current smoker).
Physical activity assessment at age 49–51 years was based on that
used for the Medical Research Council’s National Survey of
Health and Development with four categories (inactive and light,
moderate and heavy activity). Achieved education level was
classified by the highest achieved qualifications (no qualifications,
O-Level (school exit examinations at age 16 years), A-level
(school exit examinations at age 18 years), and University degree
level and above).
As the distribution of telomere length was skewed, it was log
transformed prior to analyses. Linear regression was used to assess
potential associations between log transformed telomere length
and potential predictors, and relevant assumptions were tested.
Regression coefficients (in log base pairs per unit) and corre-
sponding 95% confidence intervals (95% CI) are reported. Sex-
specific analyses and tests for interaction between sex and other
potential explanatory variables were done within the linear
regression framework. The statistical software package Stata,
version 10.0, (StataCorp, College Station: TX) was used for all
Early Predictors of Telomere Length
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Of the original 1142 study members, 832 (86% of the
surviving sample of 967 children whose families remained in
Newcastle for at least the first year of the study) were traced at
age 49–51 years
lifestyle questionnaire and telomere length was measured in 318
study members with available DNA samples (120 men, 198
women). There were no differences in early life factors between
the study sample and the remainder of the birth cohort, other
than for sex, with more women than men included.
Descriptive statistics for all variables are given in table 1. Mean
telomere length was greater in men than in women (p,0.001).
Univariate analyses showed strong associations between telomere
length and achieved adult height, waist:hip ratio and achieved
education at age 49–51 years (table 2). There was little evidence of
an association between any early life factors including standardised
or crude birth weight and telomere length (p=0.92 and 0.66
After adjusting for sex, neither achieved adult height or
waist:hipratio remained associated
(p=0.28 and 0.53 respectively). However, the negative associ-
ation between achieved education level and telomere length
remained (p=0.01). In sex-specific analyses, there were associ-
ations between telomere length and gestational age (p=0.03),
childhood growth (p=0.05) and childhood IQ (p=0.02) in
women. Achieved education level at age 49–51 years in men
was associated with telomere length (p,0.01). When compared
to the reference category of no qualifications, lesser telomere
lengths were seen for those with O and A-levels, but slightly
longer telomeres were seen in those with university qualifica-
tions. Interactions were seen between sex and both gestational
age (p=0.026) and achieved education level (p=0.05) on
telomere length. Increasing male gestational age was associated
with increased telomere length in contrast to an association
between decreased length and increasing female gestation.
There were decreasing telomere lengths for higher educational
achievement in females, but with the longest telomere lengths in
the highest achieving males. There was no evidence of
interactions between sex and any of the other explanatory
variables on telomere length.
Of the associations observed, the highest explanation of
variation in the data was seen for sex (r2=0.12). Within sex-
specific analyses, male achieved education level and female
childhood IQ and gestational age accounted for 11%, 4% and
2.4%, respectively, of the variation in log transformed telomere
length. After adjustment for sex, the resulting model including
education and interactions was found to explain 15% of the
variation in log transformed telomere length.
12. Of these, 574 completed the health and
While associations were seen between telomere length and both
achieved adult height and contemporary waist:hip ratio, neither
association was independent of sex. This is likely to be due to men
being both taller and having greater waist:hip ratios and having
longer telomeres in this cohort. An association was seen between
achieved education level and telomere length, with an interaction
with sex. Achieved education level was the only association with
telomere length in men, while gestational age, childhood IQ and
childhood growth (from birth to age nine years) were associated in
Strengths and Potential Weaknesses
The main strength of this study is the ability to analyse
prospectively collected data from different stages of life simulta-
neously. Of 1142 men and women recruited at birth in 1947, 28%
participated in the current study. Except for sex, the study sample
attending for clinical examination has been shown to be
comparable for a wide range of explanatory variables in early
life23. In addition, inclusion of cohort members who had moved
out of the study region (18% of those who attended for clinical
examination were resident outside the Northern Region of
England) increased the representativeness of the population
studied. However, the potential for participation bias in terms of
later factors remains a possibility and the study may have been
underpowered for some variables, particularly for the sex-specific
analyses. Despite the small numbers in these analyses, though, a
number of associations and interactions were identified and the
final model accounted for 15% of the variation in telomere length.
Telomere length is known to vary with age. All cohort members
were born within a two-month period and assessed when aged
between 49 and 51 years, reducing the potential for bias.
Furthermore, they were all born to mothers resident within the
city of Newcastle upon Tyne in the north east of England, so
should have less genetic and environmental heterogeneity than
would be found in a study incorporating a larger geographical
area, or one with ethnic diversity .
Comparisons with Other Studies
We have previously reported that the men in this cohort had, on
average, longer telomeres than the women at age 49–51 years
. This is contrast to the majority of other studies reporting
longer telomeres in women or no difference between men and
women [24–28]However, a recent study of Scottish 70-year-olds
also found longer telomeres in males when compared to females
.We are not aware of any cohort-specific behavioural patterns
or environmental exposures that could explain this observation,
although in the older Scottish cohort it is possible that factors such
as the selective survival of men with longer telomeres may play a
There were associations between both achieved adult height
and contemporary waist:hip ratio and telomere length at age 49–
51years in unadjusted analyses, but neither association remained
after adjustment for sex or in sex-specific analyses. For waist:hip
ratio, this is likely to reflect the larger waist:hip ratio in men
compared to women.
Although telomere length is suggested to vary between men and
women, such a difference is not apparent at birth, despite the
variability in telomere length among newborns . Very low
birth weight newborns have been found to have longer telomeres
in cord blood than low birth weight newborns , while fetal
growth restriction has been associated with reduced telomere
length . Low birth weight children have been found to have
shorter telomeres in childhood , but do not appear to have
been studied in terms of telomere length later in life. Telomere
length at age 49–51 years and both crude and standardised birth
weight were slightly greater in males than in females, though not to
the extent that they could be included in the adjusted model.
Gestational age was inversely associated with telomere length in
women. This, to our knowledge, has not previously been reported
and requires replication in other cohorts to rule out the possibility
of it being a chance finding, particularly given the number of
potential predictor variables included in this analysis.
Our finding of an association between childhood growth and
telomere length at age 49–51 years was restricted to women, with
a higher change in z-score between birth and height at age nine
Early Predictors of Telomere Length
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Table 1. Continuous descriptive statistics by sex.
VariableN Mean (SD)N Mean (SD)N Mean (SD)
Standardised birth weight (Z score)318
20.39 (0.99) 1980.01 (1.13)
Birth weight (kg)3183.37 (0.51)1203.35 (0.48) 1983.38 (0.52)
Childhood growth (change in z-scores: birth and 9 years)275
20.02 (0.49)169 0.00(0.50)
Childhood BMI (age 9 years)26916.4 (1.99)10316.4 (1.92)166 16.4(2.04)
Childhood IQ (age 11 years)266 101.6 (13.9)103 101.8 (14.3)163 101.5 (13.7)
Height at age 49–51 years (cm)314 166.1(8.44)118 173.4(6.66) 196161.7 (5.94)
BMI at age 49–51 years (kg)317 26.5 (4.69) 12026.79 (3.54)197 26.3 (5.26)
Waist : Hip ratio316 0.86 (0.10)120 0.95(0.06)196 0.80(0.06)
Percent body fat313 39.8(8.81)11936.82 (7.11)194 41.58 (9.27)
Telomere length at age 49–51 years (log base pairs)318 8.50 (0.22)120 8.59 (0.22)198 8.44 (0.20)
N Median (IQR)N Median (IQR)N Median (IQR)
Gestational Age (weeks)317 40(40,40) 11940(40,40)19840 (40,40)
Duration Breast Fed (days)31361(23,219)11961 (28,223) 19461.5 (21,219)
Pack years cigarettes3162.25(0,22.1)1198.3 (0,29.59)197 0.7 (0,17.65)
Telomere length at age 49–51 years (base pairs)3185016 (1151)1205512(1210)1984716 (1003)
Social class at birth
Smoking status age 49–51 years
Never Smoked137424134 9648
Current Smoker872831 265628
Alcohol consumption at age 49–51 years (self reported)
None381210 8 2814
Heavy 248131111 6
Social class at age 49–51 years
Physical activity at age 49–51 years
Inactive 32 1011102111
Light Activity15050 61548948
Moderate Activity6823232045 24
Heavy Activity 501718163217
Achieved education level at age 49–51 years
No Qualifications10434302674 39
O Level or equivalent105343530 70 37
A level or equivalent5819322826 13
Degree/post graduate391318 16 2111
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Table 2. Univariate associations between telomere length (log base pairs) and explanatory variables.
All, adjusted for sex
b (95% CI)
b (95% CI)
b (95% CI)
b (95% CI)
Sex (male reference category)
Standardised birth weight
Birth weight (kg)
Gestational Age (weeks)
20.03 (20.05, 20.03)
Duration Breast Fed (weeks)
20.01 (0.00, 0.01)
20.00 (0.00, 0.01)
0.00 (0.00, 0.00)
Social class at birth
Childhood IQ (age 11)
20.02 (20.04, 20.01)
Height at age 49–51 years (cm)
BMI at age 49–51 years
Waist : Hip ratio
Percent body fat
Pack years cigarettes
age 49–51 years
20.07 (20.13, 20.01)
at age 49–51 years
Social class at age
0.04 (20.11, 0.18)
Physical activity at
age 49–51 years
0.03 (20.02, 20.11)
Achieved education level at
age 49–51 years
O Level or equivalent
20.08 (20.13, 20.02)
20.08 (20.14, 20.03)
20.12 (20.22, 20.02)
A level or equivalent
20.08 (20.15, 20.01)
20.11 (20.21, 20.03)
20.01 (20.09, 20.06)
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years associated with longer telomeres. Obesity in childhood has
been reported to be associated with shorter telomere length, again
measured in childhood , but does not appear to have been
studied in relation to telomere length later in life.
Childhood IQ (in females) and achieved education level (in
males) were both associated with telomere length. The association
with educational attainment for men, in that the longest telomeres
were seen in those with the highest achieved education level, is
consistent with recent evidence reporting that the associations with
telomere length were dependent on educational attainment rather
than contemporary socio-economic circumstances [17,32]. Also
consistent with this is our previous finding of no association with
socio-economic status . Telomere length has been inconsis-
tently associated with contemporary cognitive function [29,33–
34], although not with cognitive decline . That education was
the significant factor in men while it was childhood IQ in women
may be explained by the social values of the time, where education
was not considered as important for women. Members of this
cohort were teenagers in the 1960 s when only a small percentage
of the population went to university and there were still high levels
of inequality between the sexes, with less opportunity for women to
achieve a high education level even with a relatively high IQ .
However, the lack of consistent results in the expected directions
for both males and females may also suggest that some of the
significant findings in the sex-specific analyses may be due to
chance or due to residual confounding.
Our findings suggest that, while achieved adult height and
waist:hip ratio at age 49–51 years appear to be associated with
telomere length at the same age, this is likely to reflect the
differences in these measures between men and women and thus
be due to confounding. No association was found between birth
weight and later telomere length. However, significant associations
were seen with other factors from early life. Education level was
the only predictor in males, possibly reflecting the higher
education levels in males in this generation, while telomere length
in females was associated with gestational age, childhood growth
and childhood IQ. While these findings may be due to chance, in
particular where differing associations were seen between males
and females, they do provide evidence of early life associations
with telomere length much later in life. However, they do not
support the concept of telomere length being on the pathway
between very early growth and later disease risk.
We thank all study members for taking part in this study and the study
teams and funders past and present.
Conceived and designed the experiments: LP MW TVZ JA. Performed the
experiments: CMR. Analyzed the data: MSP KDM. Wrote the paper:
MSP. Critically reviewed the manuscript and approved the final version:
MSP KDM CMR LP MW TVZ JA.
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