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Obesity, cigarette smoking, and telomere length in women



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
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 ( 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
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 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.
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. Published online June 14, 2005 DOI:10.1016/S0140-6736(05)66630-5
Lean (BMI 20)
BMI 20–30
Obese (BMI 30)
BMI category
TRF length (kb)
Q1 Q2 Q3 Q4
Quartiles of serum leptin
TRF length (kb)
Current smoker
Smoking category
TRF length (kb)
Q1 Q2 Q3 Q4
Quartiles of cigarette pack-years
TRF length (kb)
10 20 30 40 50 60 70 80
Age (years)
TRF length (kb)
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.
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.
1 Aviv A. Telomeres and human aging: facts and fibs. DOI:
10·1126/sageke.2004·51.pe43 (accessed May 25, 2005).
2 Burke A, Fitzgerald GA. Oxidative stress and smoking-induced
vascular injury. Prog Cardiovasc Dis 2003; 46: 79–90.
3 Dandona P, Alijada A, Bandyopandhyay A. Inflammation: the link
between insulin resistance, obesity and diabetes. Trends Immunol
2004; 25: 4–7.
4 Andrew T, Hart DJ, Snieder H, de Lange M, Spector TD,
MacGregor AJ. Are twins and singletons comparable? A study of
disease-related and lifestyle characteristics in adult women.
Twin Res 2001; 4: 464–77.
5 Benetos A, Okuda K, Lajemi M, et al. Telomere length as an
indicator of biological ageing: the gender effect and relation with
pulse pressure and pulse wave velocity. Hypertension 2001; 37:
6 Beltowski J, Wojcicka G, Jamroz A. Leptin decreases plasma
paraxonases 1 (PON1) activity and induces oxidative stress: the
possible novel mechanism for proatherogenic effect of chronic
hyperleptinemia. Atherosclerosis 2003; 170: 21–29. Published online June 14, 2005 DOI:10.1016/S0140-6736(05)66630-5 3
... Age dependent deficit fat free mass associated with obesity is one of major risk factor for cardio metabolic disorder. 17 The soft lean mass decreases significantly with aging, even among relatively young adults. This decrease was more noticeable among obese women who displayed greater risk of rapid decrease in lean mass as compared to normal weight. ...
... Hence, it shows that regular exercise and physiological functioning of skeletal muscle mass can be improved in older females. 17 ...
Full-text available
Aging is often associated with changes in body composition that includes total fat mass and decreased total lean body mass. In addition to changes in total fat mass, visceral or centrally located fat stores increase in size. To assess the effect of increasing age on body composition parameters in young and middle-aged healthy obese females by Body Segment Analyzer and framing preventive health measures that reduce the changes in body composition during middle age, thus setting the stage for a healthy old age. The study was conducted in Department of Physiology (CRL), BPS GMC for Women, Kanpur Kalan, Sonepat. The data for this comparative study was collected from 150 females of which 75 were of group I and 75 were of group II. Group I had cover a range from 18 to 34 years and group II had cover a range from 35 to 50 years. The present study showed, the effect of age on body fat mass, fat free mass, soft lean mass and percentage body fat was found to be highly significant (p < 0.05) but skeletal muscle mass in both the groups was not found to be significant (p = 0.434). : From the present study it was concluded that age had severe effect on body composition parameters that is body fat, fat free mass, soft lean mass and percentage body fat in obese females.
... It is not implausible that short telomere length could be associated with increased mortality from SCLC while long telomere length could be associated with risk of NSCLC-AD, as both long and short telomeres likely represent telomere dysfunction, and the histotypes are biologically distinct [52]. Furthermore, as telomere length is in uenced by genetic and non-genetic factors such as ag, exposure to cigarette smoking [47,53], it is possible that short telomere length re ects higher cumulative exposure to factors that may be associated with poorer survival. Our results not only con rmed the effect of TL on lung cancer, but also demonstrated the important role of internal and external environmental factors in the occurrence and development of the disease. ...
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Background Previous studies have observed the abnormality in telomere biology and function during the process of chronic lung diseases (CLDs). However, whether alteration of telomere length (TL) causally facilitates the incidence of CLDs remains to be determined. Therefore, we here aim to estimate the causal effect of TL on the risk of CLDs using mendelian randomization (MR) analysis. Methods Single nucleotide polymorphisms (SNPs) strongly associated with TL and CLDs were selected as genetic variables from the genome-wide association studies (GWAS). A bidirectional two-sample MR analysis primarily based on inverse variance weighted (IVW) method was then conducted to infer the causality between TL and CLDs. Cochran’s Q test and MR-Egger regression analysis were performed to assess the heterogeneity and pleiotropy, and leave-one-out analysis was tested to determine the stability of MR results. Results The forward MR analysis indicated that among non-neoplastic CLDs, elevated TL was causally related to reduced risk of asthma (OR = 0.9986, 95%CI 0.9972–0.9999, P = 0.035), chronic obstructive pulmonary disease (COPD) (OR = 0.9987, 95%CI 0.9975–0.9999, P = 0.040), idiopathic pulmonary fibrosis (IPF) (OR = 0.9971, 95%CI 0.9961–0.9980, P < 0.001), and sarcoidosis (OR = 0.6820, 95%CI 0.5236–0.8884, P = 0.005). For neoplastic CLDs, increased TL genetically predicted higher risk of non-small cell lung cancer (OR = 1.8485, 95%CI 1.4074–2.4279, P < 0.001) and lung adenocarcinoma (OR = 1.9636, 95%CI 1.2275–3.1412, P = 0.005). However, there presented no significant causality between TL and pulmonary arterial hypertension, pneumoconiosis, small cell lung cancer and squamous cell lung cancer. Moreover, reverse MR analysis all showed no obvious causalities of CLDs with TL, except for sarcoidosis (OR = 0.9936, 95%CI 0.9887–0.9984, P = 0.010). Sensitivity analyses suggested the robustness of MR results with no horizonal pleiotropy despite of partial heterogeneity in reverse MR analysis. Conclusions Our study demonstrates that TL is causally associated with decreased risk of several non-neoplastic CLDs (asthma, COPD and IPF), whereas associated with increased risk of non-small cell lung cancer (especially adenocarcinoma). There’s mutual causality between TL attrition and sarcoidosis onset. This study comprehensively elucidated the causal associations between TL and CLDs, and might provide a promising target for the prevention of these CLDs.
... Relative telomere length is quantified by telomere to singlecopy gene (T/S) ratio. Chronic inflammation, and factors that influence a pro-inflammatory milieu, such as obesity and smoking, are associated with shorter leukocyte telomere length (3,4). Shortened leukocyte telomere length is associated with increased risk of infections (5), diabetes (6), cardiac diseases (7), and all-cause mortality (8). ...
Objectives Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio).Design, Setting, Participants, and InterventionParticipants were Australians aged 60–84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation.ResultsThe mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was −0.001 (95% CI −0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration.Conclusion In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length.
... [18][19][20][21][22][23] Many factors can affect TL, including obesity, diet, lifestyle habits, stress, chronic inflammation, radiation, and genetic factors. [24][25][26][27][28] SCCOP is mainly treated with radiotherapy, which preferentially targets telomeres. It is well established that shortening telomeres increases cell sensitivity to radiation, 29 whereas elongating telomeres induces radioresistance. ...
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Background: Lymphocyte telomere length (LTL)-related genetic variants may modulate LTL and affect recurrence of squamous cell carcinoma of the oropharynx (SCCOP). Methods: A total of 1013 patients with incident SCCOP were recruited and genotyped for 16 genome-wide association study (GWAS)-identified TL-related polymorphisms. Of these patients, 489 had tumour HPV16 status determination. Univariate and multivariate analyses were performed to evaluate associations. Findings: Of the 16 TL-related polymorphisms, four were significantly associated with LTL: rs1920116, rs3027234, rs6772228, and rs11125529, and the patients with putatively favourable genotypes had approximately 1.5-3 times the likelihood of shorter LTL compared with patients with the corresponding risk genotypes. Moreover, patients with one to four favourable genotypes of the four combined polymorphisms had approximately 3-11 times the likelihood of shorter LTL compared with patients with no favourable genotype. The four LTL-related polymorphisms were significantly associated with approximately 40% reduced risk (for favourable genotypes) or doubled risk (for risk genotypes) of recurrence, and similar but more pronounced associations were observed in patients with tumour HPV16-positive SCCOP. Similarly, patients with one to four risk genotypes had significantly approximately 2.5-4 times increased recurrence risk compared with patients with no risk genotype, and similar but more pronounced associations were observed in patients with tumour HPV16-positive SCCOP. Interpretation: Four LTL-related polymorphisms individually or jointly modify LTL and risk of recurrence of SCCOP, particularly HPV-positive SCCOP. These LTL-related polymorphisms could have potential to further stratify patients with HPV-positive SCCOP for individualized treatment and better survival. Funding: Not applicable.
... This is mainly due to stable expression of telomerase in B cells. However, B cells also show progressive telomere shortening with age, which is caused by a multitude of factors, such as obesity [164], oxidative stress [165], viral infections [166], and inflammation [153]. ...
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Aging attenuates the overall responsiveness of the immune system to eradicate pathogens. The increased production of pro-inflammatory cytokines by innate immune cells under basal conditions, termed inflammaging, contributes to impaired innate immune responsiveness towards pathogen-mediated stimulation and limits antigen-presenting activity. Adaptive immune responses are attenuated as well due to lowered numbers of naïve lymphocytes and their impaired responsiveness towards antigen-specific stimulation. Additionally, the numbers of immunoregulatory cell types, comprising regulatory T cells and myeloid-derived suppressor cells, that inhibit the activity of innate and adaptive immune cells are elevated. This review aims to summarize our knowledge on the cellular and molecular causes of immunosenescence while also taking into account senescence effects that constitute immune evasion mechanisms in the case of chronic viral infections and cancer. For tumor therapy numerous nanoformulated drugs have been developed to overcome poor solubility of compounds and to enable cell-directed delivery in order to restore immune functions, e.g., by addressing dysregulated signaling pathways. Further, nanovaccines which efficiently address antigen-presenting cells to mount sustained anti-tumor immune responses have been clinically evaluated. Further, senolytics that selectively deplete senescent cells are being tested in a number of clinical trials. Here we discuss the potential use of such drugs to improve anti-aging therapy.
... In the CLPTM1L region, our results showed that the A allele variant of rs31489 was also negatively associated with LC, it was also roughly the same in Caucasians and Asians, and previous case-control studies have also reported the decrease in the frequency of rs31489 [A] in LC patients in both populations [34] [40] . It has been reported that rs31489 [A] may affect telomere length, thereby reducing the risk of LC in nonsmokers because smoking counteracts the protective effects of the A allele, shortens telomere length, and enhances telomerase activity [110] . These evidences suggest that mutations in the A allele of rs31489 regulate telomerase activity, thereby reducing the risk of LC in Caucasians and Asians. ...
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Background: Although many genome-wide association studies(GWAS) have confirmed the associations between multiple sites in the TERT-CLPTM1L region and lung cancer(LC) susceptibility in different populations, some of them haven’t found the associations between these sites and LC. The purpose of this study is to clarify the associations between TERT-CLPTM1L polymorphism and LC, as well as the differences in these associations between patients of different ethnicities and different LC subtypes. Methods: Relevant literatures published before May 7, 2022 on ‘TERT-CLPTM1L polymorphisms and LC susceptibility’ in PubMed, EMbase,Web of Science, MEDLINE databases were searched through the Internet. Statistical analysis of data was performed in Revman5.3 software, including drawing forest plots, funnel plots and so on. Sensitivity and publication bias analysis were performed in Stata 14.0 software. TSA software was performed for the Trial sequential analysis(TSA) tests to evaluate the stability of the results. Registration number: CRD42023407890. Results: A total of 51 literatures were included in this meta-analysis, including 6 TERT-CLPTM1L polymorphisms and a total of 54 studies (12 GWAS and 42 case-control studies), including 11 studies in Caucasians and 43 studies in Asians. The results showed that the minor allele variants of the 6 polymorphisms were positively or negatively associated with the risk of LC (rs2736098[T]: [OR]=1.24, 95% CI [1.18, 1.31]; rs2736100[C]: [OR]=1.25, 95% CI [1.20, 1.30]; rs31489[A]: [OR]=0.87, 95% CI [0.82, 0.92]; rs401681[T]: [OR]=0.87, 95% CI [0.84, 0.90]; rs402710[T]: [OR]=0.86, 95% CI [0.83, 0.88]; rs4975616[G]: [OR]=0.86, 95% CI [0.82, 0.91]). However, there were clear differences in these associations in LC with different pathological subtypes in Caucasian and Asian populations (Subgroup differences: I²≥50%). Conclusions: Our results confirmed the clear associations between 6 TERT-CLPTM1L polymorphisms and the risk of LC, and there were significant differences in these associations among different ethnicities/pathological subtypes of LC.
... There appear to be underlying mechanisms for the association between percent weight change and telomere length. Elevated body weight and fat are known to increase body-wide inflammation and oxidative stress, which leads to shorter telomeres [21,[48][49][50][51]. Therefore, C-reactive protein (CRP), a systemic measure of inflammation, was controlled in the current study. ...
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This investigation was designed to study the relationship between weight change over 10 years and leukocyte telomere length (LTL) in a large sample of 3070 randomly selected U.S. adults, 36–70 years old. The National Health and Nutrition Examination Survey (NHANES) data were used to examine the relationship between percent weight change and LTL. Potential mediating variables were controlled using partial correlation. After adjusting for age, race, year, and housing status, the association between percent weight change over 10 years and LTL was significant in women (F = 6.9, p = 0.0138). Adjusting for the demographic and several other covariates weakened the relationship slightly (F = 4.7, p = 0.0392). With all the covariates controlled, for each one percentage point increase in weight over the previous 10 years, telomeres were, on average, 3.48 base pairs (bp) shorter in women. Given that each one-year increase in age was associated with telomeres that were 15.0 bp shorter in women, the median weight change in U.S. women over the previous 10 years (an increase of 10.4%) was predictive of LTLs that were 36 bp shorter, on average, or an increase of 2.4 years of biological aging. Percent weight change over 10 years was not associated with LTL in U.S. men. Percent weight change over 10 years is a strong predictor of biological aging in U.S. women, but not in men.
Telomer uzunluğu yaşlanma ile ilişkili olduğu bilinen, genetik ve çevresel faktörlerden etkilenen bir biyogöstergeçtir. Telomer uzunluğunun belirlenmesinde etkili olan en önemli faktörlerden biri olan beslenme bir çevresel faktör olarak karşımıza çıkmaktadır. Oksidasyon ve inflamasyon süreçlerini etkileyerek telomerlerin uzamasına veya kısalmasına yol açabilmektedir. Anti-inflamatuvar olduğu bilinen tam tahıllar, yağlı tohumlar ile antioksidan bakımından yüksek içeriğe sahip meyveler ve sebzeler, antioksidan özelliği olan vitaminler, mineraller ve polifenoller telomerlerin uzamasına veya korunmasına yardımcı olabilirler. İnflamasyonu ve oksidasyonu arttırabilen bazı besin grupları ve besin öğeleri ise telomerlerin kısalmasına yol açabilmektedir. Bu derlemenin amacı beslenme ve telomer uzunluğunun ilişkisi ve telomerleri etkileyen potansiyel mekanizmaları incelemektir. Tam tahıllarda bulunan posa ve biyolojik aktif bileşenler, sebze ve meyvelerde bulunan antioksidanlar ve balıkta bulunan omega-3 gibi bileşenler telomerlerin uzamasına yardımcı olurken, özellikle işlenmiş ette bulunan nitrat ve nitrit gibi bileşenler telomerlerin kısalmasına yol açmaktadır. Telomer uzunluğunun diyetsel faktörler açısından korunmasında meyve ve sebzeden zengin, uygun seviyelerde kurubaklagil ve kuruyemiş içeren, kırmızı et bakımından sınırlı ve sağlıklı yağlar içeren bir diyet tüketimi oldukça önemlidir.
Diabetes mellitus is a chronic metabolic condition marked by persistent hyperglycemia. It is a major issue of public health with wide-ranging effects. Telomeres are protective caps at chromosome ends, essential for preserving genomic stability and cellular integrity. Research highlights the complex link between diabetes and telomere biology and the potential interactions between the two. This review aims to present a summary of the relationship between diabetes and telomeres, highlighting significant discoveries and probable underlying mechanisms. Telomere shortening in those with diabetes and those at risk of getting the condition provides evidence that telomere dysfunction is linked to diabetes. It is said that telomere attrition, which is influenced by elements such as oxidative stress, inflammation, insulin resistance, and hyperglycemia, plays a major role in the pathophysiology of diabetes. Diabetes Mellitus's hallmark symptoms are chronic inflammation and oxidative stress, accelerating telomere shortening via pro-inflammatory cytokines production and reactive oxygen species, respectively. Telomere dysfunction is enhanced further by the long-term effects of insulin resistance and hyperglycemia. The onset of diabetic comorbidities such as cardiovascular disease, nephropathy, retinopathy, and neuropathy has also been linked to telomere shortening. Understanding how telomeres contribute to these issues may offer new therapeutic ideas. Diabetes and its consequences may be treated with telomere-targeted medicines, such as telomerase activators, telomerase gene therapy, and treatments that target telomere-associated proteins. However, more investigation is required to assess these strategies' security, effectiveness, and long-term impacts.
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With a rapidly aging global population and improvement of outcomes with newer multiple sclerosis (MS)-specific disease-modifying therapies (DMTs), the epidemiology of MS has shifted to an older than previously described population, with a peak prevalence of the disease seen in the 55–65 years age group. Changes in the pathophysiology of MS appear to be age-dependent. Several studies have identified a consistent phase of disability worsening around the fifth decade of life. The latter appears to be independent of prior disease duration and inflammatory activity and concomitant to pathological changes from acute focal active demyelination to chronic smoldering plaques, slow-expanding lesions, and compartmentalized inflammation within the central nervous system (CNS). On the other hand, decreased CNS tissue reserve and poorer remyelinating capacity with aging lead to loss of relapse recovery potential. Aging with MS may imply longer exposure to DMTs, although treatment efficacy in patients >55 years has not been evaluated in pivotal randomized controlled trials and appears to decrease with age. Older individuals are more prone to adverse effects of DMTs, an important aspect of treatment individualization. Aging with MS also implies a higher global burden of comorbid illnesses that contribute to overall impairments and represent a crucial confounder in interpreting clinical worsening. Discontinuation of DMTs after age 55, when no evidence of clinical or radiological activity is detected, is currently under the spotlight. In this review, we will discuss the impact of aging on MS pathobiology, the effect of comorbidities and other confounders on clinical worsening, and focus on current therapeutic considerations in this age group.
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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.
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.
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.
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.
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.
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.