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Obesity, cigarette smoking, and telomere length in women

Authors:
Ana M Valdes at University of Nottingham
Ana M Valdes
Toby Andrew at Imperial College London
Toby Andrew
J.P. Gardner
J.P. Gardner
J.P. Gardner
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M Kimura
M Kimura
M Kimura
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Abstract

Obesity and smoking are important risk factors for many age-related diseases. Both are states of heightened oxidative stress, which increases the rate of telomere erosion per replication, and inflammation, which enhances white blood cell turnover. Together, these processes might accelerate telomere erosion with age. We therefore tested the hypothesis that increased body mass and smoking are associated with shortened telomere length in white blood cells. We investigated 1122 white women aged 18-76 years and found that telomere length decreased steadily with age at a mean rate of 27 bp per year. Telomeres of obese women were 240 bp shorter than those of lean women (p=0.026). A dose-dependent relation with smoking was recorded (p=0.017), and each pack-year smoked was equivalent to an additional 5 bp of telomere length lost (18%) compared with the rate in the overall cohort. Our results emphasise the pro-ageing effects of obesity and cigarette smoking.
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Research Letters
Telomeres cap the ends of chromosomes and protect
them from degradation and end-to-end fusion.
Telomeres of cultured somatic cells undergo erosion
with each cycle of replication, and oxidative stress
enhances this process.1
Both obesity and cigarette smoking are important risk
factors in many age-related diseases, and are associated
with increased oxidative stress and inflammation.2,3 The
latter process is marked by increased white blood cell
(WBC) turnover. Telomere attrition (expressed in
WBCs) can serve as a marker of the cumulative oxidative
stress and inflammation and, consequently, show the
pace of biological ageing. We therefore expected obese
individuals and smokers to have shortened telomeres.
To investigate this hypothesis we studied WBC telomere
length in 1122 healthy white women aged 18–72 years,
examining the relations with both smoking and obesity-
related phenotypes.
Participants were female twins (45 monozygotic and
516 dizygotic pairs) from the TwinsUK Adult Twin
Registry, a group previously developed to study the
heritability and genetics of diseases with a higher
prevalence among women. These women were recruited
from the general population through national media
campaigns in the UK, and were similar to age-matched
population singletons in terms of disease-related and
lifestyle characteristics (www.twinsuk.ac.uk).4In our
cohort, body-mass index (BMI) was 30 in 119 (11%)
women and 20 in 85 (8%). None of the participants
had clinical diabetes. 531 (47%) women had never
smoked, 369 (33%) were ex-smokers, 203 (18%) were
still smoking, and smoking status was unknown for 19
(2%). Smoking history was recorded with a standardised
questionnaire. Smoking exposure was measured as
pack-years=number of cigarette packs smoked per
daynumber of years smoking.
A venous blood sample was taken after an overnight
fast. We extracted DNA from WBCs, and measured
the concentration of leptin in serum with a
radioimmunoassay (Linco, St Charles, MO, USA). We
measured the mean of the terminal telomere restriction
fragment (TRF) lengths, an index of telomere length,
with the Southern blot method.5Written and oral
informed consent was obtained from all participants.
The St Thomas’ Hospital Research Ethics Committee
approved the study.
Standard linear regression techniques were used to
correlate the TRF length with age and the age-adjusted
TRF with individual factors. Log-transformed leptin
values were used for both the age-adjusted and
unadjusted linear regressions. The associations between
categorical variables and telomere length, adjusting for
age or other covariates, were assessed using analyses of
variance. To adjust for non-independence between twins
in a pair, bootstrap sets were generated by selecting a
random twin from each pair using analysis of variance,
and the p value of the mean test statistic from
100 replicates was used to confirm statistical
significance. S-Plus 6.0 (Insightful Corp) software was
used. No significant difference in the variables studied
was noted between monozygotic and dizygotic twins.
Telomere length decreased steadily with age at a mean
rate of 27 bp per year (SD 50·2; figure A) and a highly
significant negative correlation was detected (table). The
proportion of the variance in telomere length accounted
for by age was 20·6%. Squared and cubed age terms
were also added to the model and had no significant
effect on telomere length (p=0·92 and p=0·98,
respectively) suggesting a linear relation between TRF
and age.
Additionally, we noted no clear age-related difference
in rates of TRF loss; average rate of loss was 27·7 bp per
year in women aged 50 years and over and 25·7 bp
per year in those younger than 50 years.
BMI, leptin concentration in serum, and smoking
status were all significantly correlated with age (r= 0·12,
r=0·13, r=–0·10, respectively). Leptin concentration in
serum and BMI were strongly positively correlated
(r=0·76). However, the correlations between smoking
status and BMI (r=–0·05) and between leptin
concentration in serum and smoking status (r=–0·06)
were not statistically significant. BMI, leptin
concentration in serum, and packs-year of cigarettes
smoked were negatively correlated with telomere length.
The regression coefficients of these variables remained
statistically significant after adjustment for age (table).
Published online
June 14, 2005
DOI:10.1016/S0140-6736(05)
66630-5
Twin Research and Genetic
Epidemiology Unit, St Thomas’
Hospital, London, UK
(A M Valdes PhD, T Andrew PhD,
E Oelsner BSc, L F Cherkas PhD,
Prof T D Spector MD); and
Hypertension Research Center,
University of Medicine and
Dentistry of New Jersey,
Newark, New Jersey, USA
(J P Gardner PhD, M Kimura MD,
Prof A Aviv MD)
Correspondence to:
Professor T D Spector
tim.spector@kcl.ac.uk
www.thelancet.com Published online June 14, 2005 DOI:10.1016/S0140-6736(05)66630-5 1
Obesity, cigarette smoking, and telomere length in women
A M Valdes, T Andrew, J P Gardner, M Kimura, E Oelsner, L F Cherkas, A Aviv, T D Spector
Obesity and smoking are important risk factors for many age-related diseases. Both are states of heightened oxidative
stress, which increases the rate of telomere erosion per replication, and inflammation, which enhances white blood
cell turnover. Together, these processes might accelerate telomere erosion with age. We therefore tested the
hypothesis that increased body mass and smoking are associated with shortened telomere length in white blood
cells. We investigated 1122 white women aged 18–76 years and found that telomere length decreased steadily with
age at a mean rate of 27 bp per year. Telomeres of obese women were 240 bp shorter than those of lean women
(p=0·026). A dose-dependent relation with smoking was recorded (p=0·017), and each pack-year smoked was
equivalent to an additional 5 bp of telomere length lost (18%) compared with the rate in the overall cohort. Our
results emphasise the pro-ageing effects of obesity and cigarette smoking.
Research Letters
In addition to the linear models tested on continuous
measures, lean individuals were found to have
significantly longer telomeres than women with mid-
range BMIs, who, in turn, had longer telomeres than
obese individuals (figure, B; p=0·026).
Age-adjusted telomere length was negatively
correlated with log-transformed leptin concentration in
serum (table) and the mean age-adjusted telomere
length showed a progressive decrease through the
quartiles of leptin concentration (figure, C).
Individuals who had never smoked had longer age-
adjusted telomeres than former smokers and both had
longer telomeres than current smokers (figure, D;
p=0·02). Moreover, age-adjusted telomere length
decreased with the amount of cigarettes smoked (table;
figure, D). Each pack-year smoked was equivalent to a
loss of an additional 5 bp, or 18% of the average annual
loss in age-adjusted telomere length, compared with the
rate in the overall cohort.
No statistical interaction between leptin concentration
and smoking history or between BMI and smoking
history was noted. After fitting stepwise linear
regression, age, smoking (p0·0004), and leptin
(p0·006) remained significantly associated with
telomere length, but BMI did not, suggesting that the
mechanisms by which obesity affects telomere length
might be better represented by leptin concentration than
by BMI. We conclude that both obesity and smoking are
associated with shortened WBC telomere length in
women. Additionally, telomere length was inversely
correlated with the serum concentration of leptin—
a marker and regulator of body fat that itself may have
some pro-inflammatory properties known to increase
oxidative stress.6
Our findings suggest that obesity and cigarette
smoking accelerate human ageing. Our cross-sectional
data underscore the considerable variation in telomere
length between individuals. Thus large cohorts are
needed to capture the effects of inflammation and
oxidative stress.1However, in view of the hypothesis that
telomere length in vivo represents cellular turnover and
exposure to oxidative and inflammatory damage, the
difference in telomere length between being lean and
being obese corresponds to 8·8 years of ageing; smoking
(previous or current) corresponds on average to
4·6 years of ageing; and smoking a pack per day for
40 years corresponds to 7·4 years of ageing. Our results
emphasise the potential wide-ranging effects of the two
most important preventable exposures in developed
countries—cigarettes and obesity.
Contributors
A M Valdes participated in the statistical analysis and in the preparation
of the manuscript. T Andrew participated in the processing and
statistical analysis of the data. E Oelsner and L F Cherkas collected and
verified the clinical information of the study participants. J Gardner and
M Kimura did the telomere assays and participated in the processing of
the data. T D Spector and A Aviv designed and coordinated the study
and participated in the preparation of the manuscript.
2www.thelancet.com Published online June 14, 2005 DOI:10.1016/S0140-6736(05)66630-5
Lean (BMI 20)
(n=85)
BMI 20–30
(n=918)
Obese (BMI 30)
(n=119)
BMI category
TRF length (kb)
Q1 Q2 Q3 Q4
Quartiles of serum leptin
TRF length (kb)
Non-smoker
(n=531)
Ex-smoker
(n=369)
Current smoker
(n=203)
Smoking category
TRF length (kb)
6·8
7·2
7·0
7·4
7·6
7·8
6·8
7·2
7·0
7·4
7·6
7·8
6·8
7·2
7·0
7·4
7·6
7·8
6·8
7·2
7·0
7·4
7·6
7·8
Q1 Q2 Q3 Q4
Quartiles of cigarette pack-years
TRF length (kb)
5·0
5·5
6·0
6·5
7·0
7·5
8·0
8·5
9·0
9·5
10 20 30 40 50 60 70 80
Age (years)
TRF length (kb)
A
BC
DE
8·0 8·0
8·0 8·0
Figure: Relation between telomere length and (A) age, (B) BMI, (C) leptin, (D) smoking history, and
(E) cigarette pack-years
Data for B–E are age-adjusted mean TRF with SD.
Mean (SD) Correlation p Age-adjusted correlation p*
with TRF with TRF
TRF (kb) 7·06 (0·67)
Age (years) 47·77 (12·11) –0·455 0·0001 n/a n/a
BMI (kg/m2) 25·05 (4·69) –0·126 0·0001 –0·077 0·031
Serum leptin (ng/mL) 16·26 (12·50) –0·124 0·0001 –0·088 0·019
Smoking status† n/a –0·031 ns –0·087 0·017
Cigarette pack-years‡ 8·15 (14·31) –0·214 0·0001 –0·110 0·045
ns=not significant. *Statistical significance of regression coefficient from 100 bootstrap replicates. †Coded as 0=never smoked,
1=ex-smokers, 2=current smokers. ‡Among ex-smokers and current smokers only.
Table 1: Descriptive statistics of study subjects and correlations with telomere terminal restriction
fragment (TRF) length before and after adjusting for chronological age
Research Letters
Conflict of interest statement
We declare that we have no conflict of interest.
Acknowledgments
We thank all the twins participating in TwinsUK, R Swaminathan of
Chemical Pathology for the leptin assays, and Gabriela L Surdulescu for
the DNA preparation. This work was supported by the Wellcome Trust
Functional Genomics Initiative for the TwinsUK program and WT
project grant no 07495/t/Z/04/Z, the Healthcare Foundation of New
Jersey and NIH grant AG021593. The sponsor of the study had no role
in study design, data collection, data analysis, data interpretation, or
writing of the report. The corresponding author had full access to all the
data in the study and had final responsibility for the decision to submit
for publication.
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5 Benetos A, Okuda K, Lajemi M, et al. Telomere length as an
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www.thelancet.com Published online June 14, 2005 DOI:10.1016/S0140-6736(05)66630-5 3
... Model 1: unadjusted; Model 2: adjusted for gender, age, race/ethnicity, household poverty ratio, and education; Model 3: additional adjustments for BMI, total cholesterol, SII, creatinine, hypertension, diabetes, coronary heart disease, stroke, alcohol, and smoke. 95%CI, Confidence Interval physical activity levels, smoking, and obesity can influence telomere length [20][21][22][23][24]. Consistent with prior research [20][21][22][23][24], our results also indicate that gender, ethnicity, BMI, and nicotine exposure were statistically significant factors associated with telomere length. ...
... Model 1: unadjusted; Model 2: adjusted for gender, age, race/ethnicity, household poverty ratio, and education; Model 3: additional adjustments for BMI, total cholesterol, SII, creatinine, hypertension, diabetes, coronary heart disease, stroke, alcohol, and smoke. 95%CI, Confidence Interval physical activity levels, smoking, and obesity can influence telomere length [20][21][22][23][24]. Consistent with prior research [20][21][22][23][24], our results also indicate that gender, ethnicity, BMI, and nicotine exposure were statistically significant factors associated with telomere length. Previous studies have shown that alcohol consumption also affects telomere length [25], although our study did not find a statistically significant association, possibly due to the assessment of alcohol consumption relying on selfreported questionnaires, which are susceptible to recall bias. ...
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Background Telomere length is closely associated with the occurrence and development of cardiovascular and other diseases. Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel indicator of inflammation, oxidative stress, and metabolic syndrome, with some predictive ability for related disease risks in clinical practice. However, there is no research on the correlation between these two factors. Methods Using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002, we conducted analysis and research on the correlation between MHR and telomere length using the Kruskal-Wallis H test, Spearman rank correlation analysis, and partial correlation analysis. Weighted linear regression analysis assessed the strength of the association between the two variables, while restricted cubic spline regression (RCS) explored potential nonlinear relationships between them. Results The results of correlation analysis showed that MHR levels were negatively correlated with telomere length (ρ=-0.083, P < 0.001), and this relationship remained statistically significant after controlling for other covariates (P all < 0.001). Weighted linear regression analysis showed that after adjusting for all covariates, MHR remained negatively associated with telomere length (β = -0.020; 95% CI: -0.039 to -0.002; P = 0.037). Subgroup analysis shows that the negative association between MHR and telomere length appeared more striking among females (𝛽 = -0.024; 95%CI: -0.050 to 0.001; P = 0.058), the Non-Hispanic White (𝛽 = -0.022; 95%CI: -0.045 to 0.002; P = 0.066), and other race (𝛽 = -0.067; 95%CI: -0.134 to -0.000; P = 0.049). Using RCS explored potential nonlinear relationships between MHR and telomere length, revealing no nonlinear relationship between the two (P = 0.102). Conclusions This study suggests a negative correlation between MHR levels and telomere length in American adults. More comprehensive research is needed to confirm these findings in the future.
View
... In NAFLD patients, triggering factors such as obesity and insulin resistance also cause chronic liver damage and a regeneration state characterized by telomere shortening and aging in hepatocytes 12 . Obesity is also associated with chronic inflammation mediated by cytokines (and adipocytokines), increased production of reactive oxygen, nitrogen species (pro-oxidation, decreased anti-oxidation), and increased systemic oxidative stress 13,14 . ...
... Studies report that BMI was inversely correlated with TL in adults, and increased telomere abrasion and decreased TL with age were associated with increased morbidity and mortality in various diseases 27,28 . While increasing BMI resulted in higher blood volume, increased blood cells, and telomere shortening, weight loss was positively associated with telomere lengthening 13 . A recent meta-analysis examining the relationship between obesity and TL in children and adolescents has similarly shown that obesity is associated with TL shortening 29 . ...
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It is known that telomere length (TL) (evaluated with T/S ratio) is shortened in the presence of obesity. In this study, we aimed to investigate how obesity in adolescents and non-alcoholic liver disease (NAFLD) within the obese group affect TL and the clinical significance of the human telomerase reverse transcriptase (hTERT) gene MNS16A VNTR variant in terms of NAFLD. Adolescents with exogenous obesity and healthy controls (aged 10–19 years) who applied to our adolescent outpatient clinic between May-October 2023 were included in this study. We performed upper abdominal ultrasonography to investigate the presence of NAFLD in adolescents with obesity and divided into two groups: those without hepatosteatosis (obese NAFLD (-)) and those with hepatosteatosis (obese NAFLD (+)). We recorded body weight, height, waist circumference, and blood pressure measurements and measured the T/S ratio (telomere sequence copy number/gene single copy number) by the Quantitative Polymerase Chain Reaction method. The groups were compared using frequentist and Bayesian methods. Eighty-three obese adolescents [63 NAFLD(+) 20 NAFLD(-)] and 69 lean controls were included in the study. Pairwise comparisons revealed that T/S ratio was significantly lower in the obese NAFLD (-) group than the obese NAFLD (+) and the control group (p = 0.025, p = 0.007, respectively). T/S ratio was lower in the LL allele group than in the other alleles (p = 0.022) and slightly higher in the obese group with metabolic syndrome compared to the obese group without metabolic syndrome (p = 0.072). hTERT-MNS16A-VNTR gene variant LL allele had a negative correlation with T/S ratio among the obese adolescent group. Patients with LL alleles had higher ALT, GGT, HOMA-IR, and ALT/AST. Diastolic blood pressure had a significant correlation with the T/S ratio. The T/S ratio was shorter in the obese adolescent group compared to healthy ones but was higher in the NAFLD (+) obese compared to the NAFLD (-) obese. ALT level and ALT/AST ratio were higher, T/S ratio was lower in the hTERT MNS16A VNTR variant LL allele group among obese adolescents. In addition, there was a significant correlation between the T/S ratio and diastolic blood pressure in obese adolescents.
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... Chronic inflammation and diseases can also accelerate telomere shortening. [17][18][19][20][21]. Therefore, average TL is suggested as a marker of the 'biological age' of cells and the organism as a whole [16]. ...
... Valdes et al. and O'Sullivan et al. observed a direct correlation between telomere length and advancing age [19,26]. This finding was reinforced by research from Xing and colleagues, who investigated chromosome-specific telomere lengths on chromosomes 17p, 12q, 2p, and 11q in relation to esophageal cancer [51]. ...
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Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromo-some ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering in-sights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers.
View
... Telomere shortening is influenced by genetic factors like inherited telomere length and telomerase activity, lifestyle factors such as smoking, diet, and physical activity, and environmental factors including stress and exposure to pollutants. Chronic inflammation and diseases can also accelerate telomere shortening [17][18][19][20][21]. Therefore, average TL is suggested as a marker of the 'biological age' of cells and the organism as a whole [16]. ...
... Valdes et al. and O'Sullivan et al. observed a direct correlation between telomere length and advancing age [19,26]. This finding was reinforced by research from Xing and colleagues, who investigated chromosome-specific telomere lengths on chromosomes 17p, 12q, 2p, and 11q in relation to esophageal cancer [59]. ...
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Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromosome ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering insights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers.
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... Hence, telomeres act as biological clocks and regulate cell ageing. As the cell divides the telomere length keeps shortening [1]. ...
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Telomeres are vital for cellular function. Oxidative stress is detrimental to telomere function as it causes telomere attrition. Increase in oxidative stress has a negative impact on sperm telomere and chromatin integrity and therefore, on sperm function and male fertility. TERRA, a long non-coding RNA is a fundamental component required for telomere length homeostasis. Aim: The present work aimed to study the effect of H2O2 induced oxidative stress on sperm TERRA expression and chromatin function. Methodology: 5 infertile and 5 fertile males were selected for the study. Baseline semen analysis was done as per WHO manual 2021. Sperm TERRA expression was assessed by real time qPCR. To assess chromatin function nuclear chromatin decondensation test was done. Results: Study showed that 500µM H2O2 increased TERRA expression as compared to untreated groups and the difference was found to be statistically significant. As compared to controls, cases showed more fold increase in TERRA expression. When treated samples of control and cases were compared, cases had more TERRA expression than controls however, the baseline TERRA expressions in untreated samples were less in cases as compared to controls. Both comparisons yielded statistically nonsignificant results. When nuclear chromatin decondensation was compared before and after H2O2 treatment, the percentage of sperm head decondensation decreased in both cases and controls. When treated and untreated samples of cases and controls were compared, the difference was statistically nonsignificant. Conclusion: Oxidative stress led to an increase in the expression of sperm TERRA and had a negative impact on nuclear chromatin decondensation. Similar studies with greater sample size can provide much more insight into TERRA mediated regulation of telomere function and chromatin integrity and how it is affected by oxidative stress.
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... The current shift toward an aging population impacts the prevalence of noncommunicable diseases (NCD) worldwide (1). Obesity, smoking habits, excessive alcohol intake, and unhealthy dietary habits are well-known factors related to accelerated and poor-quality aging (2)(3)(4)(5)(6). On the other hand, greater adherence to healthy dietary patterns, such as the traditional Mediterranean diet (MedDiet), is associated with better quality of aging and slower telomere shortening (7,8). ...
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Objective: Life expectancy and obesity prevalence are increasing worldwide, leading to an increase in the prevalence of cardiovascular disease. High-density lipoprotein (HDL) functionality and immunosenescence play key roles in cardiovascular disease, longevity, and quality of aging. Both molecular hallmarks of aging are impacted by obesity and metabolic syndrome and can be modulated by lifestyle. We aimed to evaluate the effect of a lifestyle intervention focused on an energy-reduced Mediterranean diet (erMedDiet), physical activity (PA), and behavioral support on HDL cholesterol efflux capacity (CEC) and immunosenescence. Method: CEC and immunosenescent T cells were determined in 60 participants from the control group (CG) and 56 from the intervention group (IG) of the PREDIMED-Plus trial at baseline and after 1 and 3 years of follow-up. PREDIMED-Plus is a randomized, controlled, parallel-group trial with an IG of erMedDiet, PA promotion, and behavioral support for weight loss and a CG of usual primary care advice. The sample included 116 volunteers from the PREDIMED-Plus-IMDEA subsample of the PREDIMED-Plus trial. Men aged 55 to 75 years and women aged 60 to 75 years with a body mass index between 27 and 40 kg/m2 and metabolic syndrome were included. Results: Participants within the IG had significantly improved CEC (2.42% and 10.69% after 1 and 3 years of follow-up) and a decreased in senescent T cell profile (-3.32% ± 12.54% and -6.74% ± 11.2%, p < 0.001, after 1 and 3 years of follow-up). Baseline obesity status impacted the response to the intervention. Conclusions: A weight loss intervention program with erMedDiet and PA ameliorated senescence markers.
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... A recent metanalysis shows that telomeres shorten gradually, at a median rate of 23 bp per year until the age of 50, and then, TL shortening has a lower pace during elderly years (Ye et al., 2023). However, mean telomere length for individuals of the same age is variable and can be affected by risk factors such as tobacco consumption, stress, obesity and other lifestyle choices (Chico-Sordo et al., 2021;Polonio et al., 2020;Valdes et al., 2005;Epel et al., 2004), as well as by genetic factors, such as mutations in telomerase and other genes involved in DNA repair (Martínez and Blasco, 2017;Kong et al., 2013). All these factors lead to different proliferation potential for specific individuals at the same age and also different telomerase activity. ...
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Full-text available
  • Oct 2024
Telomeres, repetitive sequences located at the extremities of chromosomes, play a pivotal role in sustaining chromosomal stability. Telomerase is a complex enzyme that can elongate telomeres by appending telomeric repeats to chromosome ends and acts as a critical factor in telomere dynamics. The gradual shortening of telomeres over time is a hallmark of cellular senescence and cellular death. Notably, telomere shortening appears to result from the complex interplay of two primary mechanisms: telomere shelterin complexes and telomerase activity. The intricate interplay of genetic, environmental, and lifestyle influences can perturb telomere replication, incite oxidative stress damage, and modulate telomerase activity, collectively resulting in shifts in telomere length. This age-related process of telomere shortening plays a considerable role in various chronic inflammatory and oxidative stress conditions, including cancer, cardiovascular disease, and rheumatic disease. Existing evidence has shown that abnormal telomere shortening or telomerase activity abnormalities are present in the pathophysiological processes of most rheumatic diseases, including different disease stages and cell types. The impact of telomere shortening on rheumatic diseases is multifaceted. This review summarizes the current understanding of the link between telomere length and rheumatic diseases in clinical patients and examines probable telomere shortening in peripheral blood mononuclear cells and histiocytes. Therefore, understanding the intricate interaction between telomere shortening and various rheumatic diseases will help in designing personalized treatment and control measures for rheumatic disease.
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Are Twins and Singletons Comparable? A Study of Disease-related and Lifestyle Characteristics in Adult Women
Article
Full-text available
  • Dec 2001
  • Twin Res
The classic twin study is sometimes described as "the perfect natural experiment" for the investigation of the aetiology of complex disease, but assumptions of the twin design need to be empirically tested if their results are to be considered unbiased and representative of singleton populations. In this study comparisons of disease and prevalence of lifestyle characteristics have been made between twin participants in the St Thomas' Hospital UK adult twin registry, the largest twin volunteer register in the UK for the study of diseases of ageing, and a parallel population-based study of singleton women. The only differences found were for weight, where monozygotic (MZ) twins were lighter and had a smaller variance than dizygotic (DZ) twins and singletons. For the other variables studied, volunteer twins were not found to differ from age-matched singleton women in distribution or prevalence of: bone mineral density, osteoarthritis, blood pressure, hypertensive drug use, height, history of hysterectomy and ovariectomy, menopausal status and current alcohol and overall tobacco consumption. We conclude that the results of twin studies can be generalised to singleton populations for these measures and disease outcomes.
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Telomere length as indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity
Article
  • Mar 2001
  • Hypertension
Chronological age is the primary determinant of stiffness of central arteries. Increased stiffness is an independent indicator of cardiovascular risk. The aim of this study was to determine whether telomere length, a possible index of biological aging, provides a better account than chronological age for variation in arterial stiffness, evaluated by measuring pulse pressure and aortic pulse wave velocity. The study population included 193 French subjects (120 men, 73 women), with a mean age of 56+/-11 years, who were not on any antihypertensive medications. Telomere length was evaluated in white blood cells by measuring the mean length of the terminal restriction fragments. Age-adjusted telomere length was longer in women than in men (8.67+/-0.09 versus 8.37+/-0.07 kb; P=0.016). In both genders, telomere length was inversely correlated with age (P<0.01). Multivariate analysis showed that in men, but not in women, telomere length significantly contributed to pulse pressure and pulse wave velocity variations. In conclusion, telomere length provides an additional account to chronological age of variations in both pulse pressure and pulse wave velocity among men, such that men with shorter telomere length are more likely to exhibit high pulse pressure and pulse wave velocity, which are indices of large artery stiffness. The longer telomere length in women suggests that for a given chronological age, biological aging of men is more advanced than that of women.
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Oxidative stress and smoking-induced vascular injury
Article
  • Jul 2003
  • PROG CARDIOVASC DIS
The relative importance of mechanisms relevant to smoking-induced vascular injury is poorly understood. Cigarette smoke is a source of free radicals but also results in cellular activation and consequent generation of free radicals in vivo. Here we consider several approaches to estimating the consequences of free radical generation in vivo, using measurements of modified lipids, proteins, and DNA. Smoking appears to result in elevation of several biomarkers of oxidant stress, some in a dose-related fashion. There is also some evidence that disordered endothelial function in smokers may be partly attributable to oxidant stress. Other effects of smoking on hemostatic activation, sympathoadrenal function, and lipoprotein structure and function may also be modulated by smoking-induced oxidant stress. The emergence and application of rational quantitatively reliable indexes of oxidant stress in vivo is likely to elucidate the relative contribution of oxidant stress to smoking-induced vascular injury.
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Leptin decreases plasma paraoxonase 1 (PON1) activity and induces oxidative stress: The possible novel mechanism for proatherogenic effect of chronic hyperleptinemia
Article
  • Oct 2003
  • Atherosclerosis
Obesity is an important risk factor of atherosclerosis; however, the mechanism of proatherogenic effect of obesity is not definitely established. Recent studies suggest an important role of leptin in obesity associated complications. We investigated the effect of chronic hyperleptinemia on two antioxidant enzymes contained in plasma lipoproteins: paraoxonase 1 (PON1) and platelet activating factor-acetylhydrolase (PAF-AH). The study was performed on three groups of male Wistar rats: (1) control, fed ad libitum, (2) leptin treated, receiving leptin (0.25 mg/kg twice daily s.c. for 7 days), (3) pair-fed, in which food intake was identical as in leptin-treated animals. PON1 activity toward paraoxon, phenyl acetate, gamma-decanolactone and homogentisic acid lactone was lower in leptin-treated than in control group by 30.4, 30.8, 34.5 and 62%, respectively. Leptin increased plasma concentration and urinary excretion of isoprostanes by 46.4 and 49.2%, respectively. Leptin treatment had no effect on plasma lipid profile and glucose level. Plasma leptin was 208.8% higher in leptin-treated and 51.5% lower in pair-fed than in control group. These data indicate that hyperleptinemia induced by exogenous leptin administration markedly decreases plasma PON1 activity and induces oxidative stress. These mechanisms may be involved in atherogenesis in hyperleptinemic obese individuals.
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Inflammation: The link between insulin resistance, obesity and diabetes
Article
  • Feb 2004
  • TRENDS IMMUNOL
Recent data have revealed that the plasma concentration of inflammatory mediators, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), is increased in the insulin resistant states of obesity and type 2 diabetes, raising questions about the mechanisms underlying inflammation in these two conditions. It is also intriguing that an increase in inflammatory mediators or indices predicts the future development of obesity and diabetes. Two mechanisms might be involved in the pathogenesis of inflammation. Firstly, glucose and macronutrient intake causes oxidative stress and inflammatory changes. Chronic overnutrition (obesity) might thus be a proinflammatory state with oxidative stress. Secondly, the increased concentrations of TNF-alpha and IL-6, associated with obesity and type 2 diabetes, might interfere with insulin action by suppressing insulin signal transduction. This might interfere with the anti-inflammatory effect of insulin, which in turn might promote inflammation.
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Telomeres and Human Aging: Facts and Fibs
Article
  • Jan 2005
  • Sci Aging Knowl Environ
Can telomere dynamics, defined by telomere length and attrition rate, provide information about the biology of human aging above and beyond that provided by chronological age? Accruing data suggest that it can. White blood cells (WBCs) have been used as the primary model in attempts to decipher links between aging, aging-related disorders, and telomere dynamics in humans. The WBC model may be appropriate in clinical settings, provided that we fully appreciate its drawbacks and limitations. On the basis of WBC telomere data, it is evident that age-adjusted telomere length is highly variable, highly heritable, longer in women than men, and shorter in people who harbor a host of age-related disorders, whose common denominators may prove to be increased oxidative stress and inflammation. It appears that shorter age-adjusted WBC telomere length augurs a greater risk of morbidity and premature mortality in the elderly. However, it is unsettled whether human telomere dynamics is only a proxy for fundamental mechanisms that govern the course of aging or a key determinant in its progression.
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