Cellular aging and pregnancy complications: Examining maternal leukocyte telomere length in two diverse cohorts.

Introduction: The aging process in children and adolescents is accelerated resulting in the premature development of “adult” diseases such as hypertension and diabetes. Telomere shortening plays a key role in human aging; identifying factors that regulate this process is important for developing effective lifestyle interventions so as to prevent and treat age-associated diseases. In vitro and in vivo studies demonstrate that high salt content markedly decreases life span, and accelerates cellular aging through increased DNA breakage. However, the effect of high salt diet on telomere length, a marker of biological aging, remains unknown. Therefore, we aimed to test the hypothesis that high dietary sodium intake is inversely associated with leukocyte telomere length, especially in the context of obesity. Methods: Leukocyte telomere length (T/S ratio) was assessed by a quantitative polymerase chain reaction method in 766 adolescents aged 14-18 years (50% female, 49% African Americans). Diet was assessed with three to seven 24-h recalls, and physical activity was determined by accelerometry. Participants were classified according to low vs. high sodium intake (below or above the median), and according to weight status (normal vs. overweight/obese). Analysis of covariance and linear regression analyses were used to determine the effects of sodium intake and weight status on leukocyte telomere length. Results: After controlling for age, sex, race, energy intake, Tanner stage, and vigorous physical activity, a statistically significant sodium intake by weight status interaction was observed, such that leukocyte telomere length was significantly shorter in the high sodium intake vs. low sodium intake subjects from the overweight/obese group (1.24 ± 0.22 vs. 1.32 ± 0.21, p=0.02), but not the normal weight group (1.29 ± 0.24 vs. 1.30 ± 0.24, p=0.69). Consistent with the low vs. high sodium intake group data, multiple linear regression analyses, adjusting for age, sex, race, energy intake, Tanner stage and vigorous physical activity, revealed that higher dietary sodium intake was associated with shorter leukocyte telomere length in the overweight/obese group (β=-0.37, p=.045), but not the normal weight group. Conclusion: High dietary sodium intake is associated with shorter telomere length in overweight and obese adolescents suggesting that high sodium intake and obesity may act synergistically to accelerate cellular aging. Longitudinal studies are warranted to determine the synergistic effect of high sodium intake and obesity on telomere shortening over time.

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Delay discounting, genetic sensitivity, and leukocyte telomere length

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1514351113 ◽

2016 ◽

Vol 113 (10) ◽

pp. 2780-2785 ◽

Cited By ~ 15

Author(s):

Onn-Siong Yim ◽

Xing Zhang ◽

Idan Shalev ◽

Mikhail Monakhov ◽

Songfa Zhong ◽

...

Keyword(s):

Decision Making ◽

Estrogen Receptor ◽

Telomere Length ◽

Delay Discounting ◽

Receptor Gene ◽

Cellular Aging ◽

Leukocyte Telomere Length ◽

Psychological Resources ◽

Oxytocin Receptor Gene ◽

The Relationship

In a graying world, there is an increasing interest in correlates of aging, especially those found in early life. Leukocyte telomere length (LTL) is an emerging marker of aging at the cellular level, but little is known regarding its link with poor decision making that often entails being overly impatient. Here we investigate the relationship between LTL and the degree of impatience, which is measured in the laboratory using an incentivized delay discounting task. In a sample of 1,158 Han Chinese undergraduates, we observe that steeper delay discounting, indexing higher degree of impatience, is negatively associated with LTL. The relationship is robust after controlling for health-related variables, as well as risk attitude—another important determinant of decision making. LTL in females is more sensitive to impatience than in males. We then asked if genes possibly modulate the effect of impatient behavior on LTL. The oxytocin receptor gene (OXTR) polymorphism rs53576, which has figured prominently in investigations of social cognition and psychological resources, and the estrogen receptor β gene (ESR2) polymorphism rs2978381, one of two gonadal sex hormone genes, significantly mitigate the negative effect of impatience on cellular aging in females. The current results contribute to understanding the relationship between preferences in decision making, particularly impatience, and cellular aging, for the first time to our knowledge. Notably, oxytocin and estrogen receptor polymorphisms temper accelerated cellular aging in young females who tend to make impatient choices.

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Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging

Neuroscience & Biobehavioral Reviews ◽

10.1016/j.neubiorev.2015.05.007 ◽

2015 ◽

Vol 55 ◽

pp. 333-364 ◽

Cited By ~ 153

Author(s):

Daniel Lindqvist ◽

Elissa S. Epel ◽

Synthia H. Mellon ◽

Brenda W. Penninx ◽

Dóra Révész ◽

...

Keyword(s):

Mental Illness ◽

Psychiatric Disorders ◽

Telomere Length ◽

Cellular Aging ◽

Leukocyte Telomere Length ◽

Underlying Mechanisms

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Leukocyte Telomere Length Independently Predicts 3-Year Diabetes Risk in a Longitudinal Study of Chinese Population

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/9256107 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Yiwen Liu ◽

Chifa Ma ◽

Pingping Li ◽

Chunxiao Ma ◽

Shuli He ◽

...

Keyword(s):

Oxidative Stress ◽

Risk Factors ◽

Longitudinal Study ◽

Telomere Length ◽

Diabetes Risk ◽

Cellular Aging ◽

Leukocyte Telomere Length ◽

Sod Activity ◽

Diabetes Risk Factors

Cellular aging markers, including telomere length and mitochondrial function, as well as oxidative stress and inflammation markers influence each other and form a complex network, which is affected in diabetes. However, it remains unknown whether these markers could independently predict future diabetes after adjustment for their mutual effects. We conducted a 3-year longitudinal study in a Chinese cohort that comprised 108 nondiabetic individuals at baseline. The 2-hour 75 g oral glucose tolerance tests were performed at baseline and at 3-year follow-up. At baseline, leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) in leukocytes were determined using the polymerase chain reaction method. Tumor necrosis factor (TNF-α), interleukin-6, 8-hydroxy-2-deoxyguanosine levels, and superoxide dismutase (SOD) activity were measured by the enzyme-linked immunosorbent assay. Participants who developed diabetes at the 3-year follow-up (n=28) had shorter LTL and higher levels of TNF-α and SOD activity at baseline. Baseline LTL was found to be independently associated with the development of diabetes at the 3-year follow-up after the adjustment for mtDNAcn, markers of oxidative stress and inflammation, and conventional diabetes risk factors. Our findings suggest that LTL is an independent predictor for 3-year diabetes risk, which might inform timely prevention and treatment of diabetes. Telomere shortening might be involved in the pathogenesis of diabetes independently of conventional diabetes risk factors, mtDNAcn, or oxidative stress and inflammation pathways.

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Depressive and anxiety disorders and short leukocyte telomere length: mediating effects of metabolic stress and lifestyle factors

Psychological Medicine ◽

10.1017/s0033291716000891 ◽

2016 ◽

Vol 46 (11) ◽

pp. 2337-2349 ◽

Cited By ~ 23

Author(s):

D. Révész ◽

J. E. Verhoeven ◽

Y. Milaneschi ◽

B. W. J. H. Penninx

Keyword(s):

Cigarette Smoking ◽

Anxiety Disorders ◽

Telomere Length ◽

Symptom Severity ◽

Lifestyle Factors ◽

Lifestyle Changes ◽

Cellular Aging ◽

Leukocyte Telomere Length ◽

Metabolic Alterations ◽

The Relationship

BackgroundDepressive and anxiety disorders are associated with shorter leukocyte telomere length (LTL), an indicator of cellular aging. It is, however, unknown which pathways underlie this association. This study examined the extent to which lifestyle factors and physiological changes such as inflammatory or metabolic alterations mediate the relationship.MethodWe applied mediation analysis techniques to data from 2750 participants of the Netherlands Study of Depression and Anxiety. LTL was assessed using quantitative polymerase chain reaction. Independent variables were current depressive (30-item Inventory of Depressive Symptoms – Self Report) and anxiety (21-item Beck's Anxiety Inventory) symptoms and presence of a depressive or anxiety disorder diagnosis based on DSM-IV; mediator variables included physiological stress systems, metabolic syndrome components and lifestyle factors.ResultsShort LTL was associated with higher symptom severity (B = −2.4, p = 0.002) and current psychiatric diagnosis (B = −63.3, p = 0.024). C-reactive protein, interleukin-6, waist circumference, triglycerides, high-density lipoprotein cholesterol and cigarette smoking were significant mediators in the relationship between psychopathology and LTL. When all significant mediators were included in one model, the effect sizes of the relationships between LTL and symptom severity and current diagnosis were reduced by 36.7 and 32.7%, respectively, and the remaining direct effects were no longer significant.ConclusionsPro-inflammatory cytokines, metabolic alterations and cigarette smoking are important mediators of the association between depressive and anxiety disorders and LTL. This calls for future research on intervention programs that take into account lifestyle changes in mental health care settings.

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Association of a biomarker-based frailty index with telomere length in older US adults: Findings from NHANES 1999-2002

10.1101/191023 ◽

2017 ◽

Cited By ~ 1

Author(s):

Ghalib A. Bello ◽

Yueh-Hsiu M. Chiu ◽

Gerard G. Dumancas

Keyword(s):

Linear Regression ◽

Laboratory Test ◽

Telomere Length ◽

Cellular Senescence ◽

Frailty Index ◽

Cellular Aging ◽

Leukocyte Telomere Length ◽

Study Results ◽

Multiple Covariates ◽

The Relationship

ABSTRACTObjectivesTo study the link between frailty and cellular senescence, we examine the association of leukocyte telomere length (LTL) with a recently introduced measure of subclinical frailty that is based entirely on laboratory test biomarkers (FI-LAB).MethodsThis study was conducted on a random sample of 1890 Americans aged 60+. Multiple Linear Regression was used to examine the relationship between FI-LAB and LTL.ResultsA statistically significant association was found between FI-LAB and LTL after adjusting for multiple covariates, indicating that higher FI-LAB scores are associated with shorter telomeres.DiscussionOur study results establish a link between subclinical frailty (FI-LAB) and cellular aging, which may help elucidate the pathophysiological mechanisms giving rise to frailty.

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Adiposity and Leukocyte Telomere Length in US Adults by Sex-Specific Race/Ethnicity: National Health and Nutrition Examination Survey

Ethnicity & Disease ◽

10.18865/ed.30.3.441 ◽

2020 ◽

Vol 30 (3) ◽

pp. 441-450 ◽

Cited By ~ 1

Author(s):

Sharon K. Davis ◽

Ruihua Xu ◽

Rumana J. Khan ◽

Amadou Gaye

Keyword(s):

Telomere Length ◽

National Health ◽

Mexican American ◽

White Women ◽

The United States ◽

Cellular Aging ◽

Leukocyte Telomere Length ◽

Health And Nutrition ◽

Race Ethnicity ◽

Total Body

Objective: Little is known about the relationship between adiposity and telomere length in the United States population. The objective of our research was to examine this relationship in a representative, socioeconomically and sex-specific, diverse racial/ethnic population in the United States.Design: Cross-sectional.Methods: Body mass index (BMI), % total body fat (TBF) and waist circumference (WC) with leukocyte telomere length (LTL) were examined according to sex-specific race/ethnicity using separate adjusted multivariate linear regressions on a sample of 4,919 respondents aged 20-84 years from the National Health and Nutrition Examination Survey’s 1999-2002 data.Results: LTL was shortened .41%, .44%, and .16% in African American (AA) women and was associated with increasing BMI, %TBF, and WC, (β:-.0041, 95%CI: -.0070, -.0012; P=.007; β:-.0044, 95% CI: -.0081, -.0007; P=.02; β:-.0016, 95%CI: -.0031, -.0001; P=.04, respectively). LTL was shortened .29% in White women and was associated with increasing %TBF (β:-.0029, 95%CI: -.0048, -.0009; P=.006). There were no associations among AA men, White men or Mexican American men and women.Conclusions: LTL is associated with an obesity phenotype in AA women. Tailored intervention is needed to ameliorate the burden of excess adiposity and subsequent cellular aging. Ethn Dis. 2020;30(3):441-450; doi:10.18865/ed.30.3.441

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Abstract P079: Sugar-Sweetened Soda Consumption is Associated with Shorter Leukocyte Telomere Length among Healthy Adults

Circulation ◽

10.1161/circ.129.suppl_1.p079 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Cindy W Leung ◽

Barbara A Laraia ◽

Belinda L Needham ◽

David H Rehkopf ◽

Nancy E Adler ◽

...

Keyword(s):

Metabolic Disease ◽

Telomere Length ◽

Fruit Juice ◽

Sugar Content ◽

Individual Characteristics ◽

Healthy Adults ◽

Cellular Aging ◽

Cell Aging ◽

Prior History ◽

Leukocyte Telomere Length

Consumption of sugar-sweetened beverages (SSBs) is linked to increased risks of metabolic disease, but the biological mechanisms underlying this association are still under investigation. Leukocyte telomere length maintenance underlies healthy cellular aging, and may provide a link between SSB consumption and risk of disease. Given the known effects of SSBs on oxidative stress and insulin resistance, we examined the associations between sugar-sweetened beverage, diet soda, and fruit juice consumption, and leukocyte telomere length in 5,309 healthy adults with no prior history of diabetes or cardiovascular disease, using data from the 1999-2002 National Health and Nutrition Surveys (NHANES). We hypothesized that beverages with high sugar content would be most detrimental to cellular aging. Leukocyte telomere length was assayed from DNA specimens collected from adult NHANES participants. Diet was assessed using 24-hour dietary recalls. Because 24-hour dietary recalls may not accurately reflect long-term intake, the National Cancer Institute statistical method was used to estimate usual dietary intake. After adjustment for sociodemographic characteristics, smoking behavior, physical activity, dietary quality, and body mass index (BMI), each 8-ounce daily serving of sugar-sweetened sodas was associated with shorter telomeres (β=-0.010, 95% CI -0.019, -0.001), roughly equivalent to 1.8 additional years of aging. Twenty-one percent of study participants consumed ≥20 ounces of sugar-sweetened soda a day, translating into approximately 4.4 additional years of aging for heavy soda drinkers. No significant associations were observed between consumption of diet sodas, non-carbonated SSBs, or 100% fruit juice and telomere length. In conclusion, regular consumption of sugar-sweetened sodas was associated with shorter telomeres in a nationally representative sample of healthy, nonelderly adults independent of BMI and other individual characteristics. These results suggest that SSBs may influence metabolic disease development through accelerated cell aging. Although more research is needed to confirm these associations, these findings strengthen the rationale for limiting the consumption of SSBs.

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