Shorter telomeres are associated with obesity and weight gain in the elderly.
ABSTRACT Objective:Obesity and shorter telomeres are commonly associated with elevated risk for age-related diseases and mortality. Whether telomere length (TL) may be associated with obesity or variations in adiposity is not well established. Therefore, we set out to test the hypothesis that TL may be a risk factor for increased adiposity using data from a large population-based cohort study.Design:Levels of adiposity were assessed in six ways (obesity status, body mass index (BMI), the percentage of body fat or % body fat, leptin, visceral and subcutaneous fat mass) in 2721 elderly subjects (42% black and 58% white). Associations between TL measured in leukocytes at baseline and adiposity traits measured at baseline, and three of these traits after 7 years of follow-up were tested using regression models adjusting for important covariates. Additionally, we look at weight changes and relative changes in BMI and % body fat between baseline and follow-up.Results:At baseline, TL was negatively associated with % body fat (ß=-0.35±0.09, P=0.001) and subcutaneous fat (ß=-2.66±1.07, P=0.01), and positively associated with leptin after adjusting for % body fat (ß=0.32±0.14, P=0.001), but not with obesity, BMI or visceral fat. Prospective analyses showed that longer TL was associated with positive percent change between baseline and 7-year follow-up for both BMI (ß=0.48±0.20, P=0.01) and % body fat (ß=0.42±0.23, P=0.05).Conclusion:Our study suggests that shorter TL may be a risk factor for increased adiposity. Coupling with previous reports on their reversed roles, the relationship between adiposity and TL may be complicated and may warrant more prospective studies.
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ABSTRACT: Adipocyte hypertrophy and hyperplasia have been shown to be associated with shorter telomere length, which may reflect aging, altered cell proliferation and adipose tissue (AT) dysfunction. In individuals with obesity, differences in fat distribution and AT cellular composition may contribute to obesity related metabolic diseases. Here, we tested the hypotheses that telomere lengths (TL) are different between: (1) abdominal subcutaneous and omental fat depots, (2) superficial and deep abdominal subcutaneous AT (SAT), and (3) adipocytes and cells of the stromal vascular fraction (SVF). We further asked whether AT TL is related to age, anthropometric and metabolic traits. TL was analyzed by quantitative PCR in total human genomic DNA isolated from paired subcutaneous and visceral AT of 47 lean and 50 obese individuals. In subgroups, we analyzed TL in isolated small and large adipocytes and SVF cells. We find significantly shorter TL in subcutaneous compared to visceral AT (p<0.001) which is consistent in men and subgroups of lean and obese, and individuals with or without type 2 diabetes (T2D). Shorter TL in SAT is entirely due to shorter TL in the SVF compared to visceral AT (p<0.01). SAT TL is most strongly correlated with age (r=-0.205, p<0.05) and independently of age with HbA1c (r=-0.5, p<0.05). We found significant TL differences between superficial SAT of lean and obese as well as between individuals with our without T2D, but not between the two layers of SAT. Our data indicate that fat depot differences in TL mainly reflect shorter TL of SVF cells. In addition, we found an age and BMI-independent relationship between shorter TL and HbA1c suggesting that chronic hyperglycemia may impair the regenerative capacity of AT more strongly than obesity alone. Copyright © 2015. Published by Elsevier Inc.Biochemical and Biophysical Research Communications 01/2015; DOI:10.1016/j.bbrc.2014.12.122 · 2.28 Impact Factor
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ABSTRACT: Context Metabolic Syndrome (MetS) clusters risk factors for age-related conditions including cardiovascular disease and diabetes. Shorter telomere length (TL), a cellular marker for biological age, may predict an individual's deteriorating metabolic condition. Objective We examined whether shorter baseline TL is associated with a worse metabolic profile and with less favorable trajectories of MetS components over a six-year follow-up. Design and setting Participants were part of the Netherlands Study of Depression and Anxiety, an ongoing prospective cohort study with six years follow-up. Participants This study included 2848 participants aged 18-65 years. Main outcome measures Baseline TL from leukocytes was determined using quantitative polymerase chain reaction, and MetS components (waist circumference, triglycerides, high-density lipoprotein (HDL) cholesterol, systolic blood pressure (SBP) and fasting glucose) were determined at baseline, and after two and six years. Cross-sectional and longitudinal analyses were adjusted for relevant sociodemographic, lifestyle and health factors. Results Shorter baseline TL was cross-sectionally associated with HDL (β=-0.016, SE=0.008, p=.05), waist circumference (β=0.647, SE=0.238, p=.007), triglycerides (β=0.038, SE=0.009, p<.001), and fasting glucose (β=0.011, SE=0.003, p<.001), as well as with the total number of MetS components (β=0.075, SE=0.023, p=.001) and the presence of MetS (OR=1.19, 95% CI=1.07-1.33; p=.002). Although baseline differences progressively reduced over time, shorter baseline TL was still significantly associated with unfavourable scores of most MetS components at the two- or six-year follow-ups. Conclusions Cellular aging, as assessed by TL, is associated with a higher metabolic risk profile which maintains to be unfavorable even after a period of six years. These findings suggest that cellular aging might play a role in the onset of various aging-related somatic diseases via its effect on metabolic alterations.Journal of Clinical Endocrinology & Metabolism 09/2014; DOI:10.1210/jc.2014-1851 · 6.31 Impact Factor
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ABSTRACT: Human telomeres are tandem repeats of DNA (5'-TTAGGG-3') and a complex of associated proteins, called shelterin (e.g. telomeric repeat factors 1 and 2, TRF1 and TRF2) (1). This complex structure is responsible for protecting the chromosome end from nucleolytic degradation, chromosome end-to-end fusion and breakage-fusion-bridge-cycle (2). Due to the semiconservative replication of the DNA, in each cell division, a small portion of the DNA at 5' end chromosome is not replicated (3). Due to its high guanine content, telomeric DNA is highly susceptible to accumulation of oxidative stress induction of 8-oxo-guanine which is not efficiently repaired and may lead to reduced binding of TRF1 and TRF2 causing telomere dysfunction (4, 5). Furthermore, random accumulation of single-strand breaks resulting from hydroxyl radical attack on the DNA backbone all along the telomere and in subtelomeric regions leads to accelerated telomere shortening or complete loss of telomeres, respectively (6). Therefore, in normal somatic tissues, telomeres shorten and/or become dysfunctional with age (6), and this process can be accelerated by poor lifestyle and diet (7, 8), as well as by exposure to environmental and occupational factors (9). Both extremely short and long telomeres have been associated with neurodegenerative and cardiovascular diseases, cancer risk (10), and with some polymorphisms (11). Telomeres have become an important issue in relation to healthy aging because their dysfunction leads to genomic instability, triggering senescence and accelerating age-related diseases (12, 13). What is known, so far, is that a diet rich in folate, omega-3 fatty acids, vitamin D, cereal fiber and use of multivitamins can help to maintain stable and functional telomeres. On the other hand, the intake of polyunsaturated fatty acids, processed meat and high homocysteine plasma levels, a metabolic indicator of folate deficiency, are associated with shorter telomeres (for a review, see reference 8). Results show that obesity can also be related to shorter telomeres (14), which is plausible because excessive accumulation of adipose tissue and associated metabolic imbalances, increases oxidative stress and can deregulate inflammatory cytokines. Chronic heart failure and coronary artery disease are strongly associated with inflammation and, as anticipated, have been linked with telomere shortening as well (10). There is growing evidence that telomere stability can be affected by occupational and environmental exposures, since some of these factors have been correlated with chronic diseases and inflammation. The environmental and occupational exposures linked to shorter telomeres include polycyclic aromatic hydrocarbons (PAHs), benzene and toluene, particulate matter and lead long-term exposure (for a review, see reference 9). PAHs are known for generating DNA adducts and, therefore, genomic instability. Lead induces double-strand breaks in DNA, particularly on the telomere lagging strand (for a review, see reference 9). Not all the mechanisms of action of these chemicals are already elucidated, but in almost all cases, the induction of oxidative stress and reactive oxygen species appears to be involved. Moreover, telomere shortening is a risk factor for several kinds of cancers (15). As previously stated, longer telomeres can also represent a health problem. For example, a recent study showed that folate deficiency leads to longer but dysfunctional telomeres associated with increased chromosomal instability possibly as a result of DNA hypomethylation (16). Persistent organic pollutants were associated with telomere elongation, but the mechanism is still unknown. Increased telomerase activity and, therefore, longer telomeres were observed in exposure to arsenic (for a review, see reference 9). Telomere dynamics also seems to be associated with psychological and psychosocial effects. Some authors observed that telomere shortening was associated with childhood chronic or serious illness, besides adverse lifetime events, as anxiety disorder and childhood maltreatment, resulting in shorter telomeres at adult life (7, 17). These results may indicate that childhood adversities might have a considerable impact on well being in later life. Higher stress levels in relation to psychosocial effects and higher average levels of depressive symptoms were observed in caregivers of Alzheimer's patients, and shortened telomeres were found (for a review see reference 7). Finally, telomeric DNA is relatively less capable of repair, resulting in accelerated telomere shortening during the cell cycle and replicative senescence (12). It is recognized that diet plays an important role on telomere maintenance, and