scholarly journals Genetically Increased Telomere Length and Aging-Related Traits in the U.K. Biobank

2019 ◽  
Vol 76 (1) ◽  
pp. 15-22
Author(s):  
Kathryn Demanelis ◽  
Lin Tong ◽  
Brandon L Pierce
Keyword(s):  
Blood Pressure ◽  
Telomere Length ◽  
Simulated Data ◽  
Forced Expiratory Volume ◽  
Nucleotide Polymorphisms ◽  
Middle Aged ◽  
Standard Deviation Increase ◽  
Age Related ◽  
Potential Biomarker ◽  
The Impact

Abstract Telomere length (TL) shortens over time in most human cell types and is a potential biomarker of aging. However, the causal association of TL on physical and cognitive traits that decline with age has not been extensively examined in middle-aged adults. Using a Mendelian randomization (MR) approach, we utilized genetically increased TL (GI-TL) to estimate the impact of TL on aging-related traits among U.K. Biobank (UKB) participants (age 40–69 years). We manually curated 53 aging-related traits from the UKB and restricted to unrelated participants of British ancestry (n = 337,522). We estimated GI-TL as a linear combination of nine TL-associated single nucleotide polymorphisms (SNPs), each weighted by its previously-reported association with leukocyte TL. Regression models were used to assess the associations between GI-TL and each trait. We obtained MR estimates using the two-sample inverse variance weighted (IVW) approach. We identified six age-related traits associated with GI-TL (Bonferroni-corrected threshold p < .001): pulse pressure (PP) (p = 5.2 × 10-14), systolic blood pressure (SBP) (p = 2.9 × 10-15), diastolic blood pressure (DBP) (p = 5.5 × 10-6), hypertension (p = 5.5 × 10-11), forced expiratory volume (FEV1) (p = .0001), and forced vital capacity (FVC) (p = 3.8 × 10-6). Under MR assumptions, one standard deviation increase in TL (~1,200 base pairs) increased PP, SBP, and DBP by 1.5, 2.3, and 0.8 mmHg, respectively, while FEV1 and FVC increased by 34.7 and 52.2 mL, respectively. The observed associations appear unlikely to be due to selection bias based on analyses including inverse probability weights and analyses of simulated data. These findings suggest that longer TL increases pulmonary function and blood pressure traits among middle-aged UKB participants.

scholarly journals Genetically Increased Telomere Length and Aging-related Physical and Cognitive Traits in the UK Biobank

2019 ◽  
Author(s):  
Kathryn Demanelis ◽  
Lin Tong ◽  
Brandon L. Pierce
Keyword(s):  
Blood Pressure ◽  
Pulmonary Function ◽  
Telomere Length ◽  
Regression Models ◽  
Simulated Data ◽  
Uk Biobank ◽  
Inverse Probability Weights ◽  
Age Related ◽  
Potential Biomarker ◽  
The Uk

ABSTRACTBackgroundTelomere length (TL) shortens over time in most human cell types and is a potential biomarker aging. However, the causal impact of TL on physical and cognitive phenotypes that decline with age has not been extensively examined. Using a Mendelian randomization (MR) approach, we utilized genetically increased TL (GI-TL) to estimate the impact of TL on aging-related traits among UK Biobank (UKB) participants.MethodsWe manually curated >50 aging-related traits from UKB and restricted to unrelated participants of British ancestry (n=337,522). We estimated GI-TL as a linear combination of nine TL-associated SNPs, each weighted by its previously-reported association with leukocyte TL. Regression models were used to assess the associations between GI-TL and each trait. We obtained MR estimates using the two-sample inverse variance weighted (IVW) approach.ResultsWe identified 5 age-related traits associated with GI-TL (Bonferroni-corrected threshold p<0.001): pulse pressure (PP) (p=5.2×10−14), systolic blood pressure (SBP) (p=2.9×10−15), diastolic blood pressure (DBP) (p=5.5×10−6), forced expiratory volume (FEV1) (p= p=0.0001), and forced vital capacity (FVC) (p=3.8×10−6). Under MR assumptions, one standard deviation increase in TL (∼1200 base pairs) increased PP, SBP, and DBP by 1.5, 2.3, and 0.8 mmHg, respectively, while FEV1 and FVC increased by 34.7 and 52.2 mL, respectively. The observed associations appear unlikely to be due to selection bias based on analyses including inverse probability weights and analyses of simulated data.ConclusionsThese findings suggest that longer TL increases pulmonary function and blood pressure traits. Further research is necessary to evaluate TL in cardiovascular and pulmonary age-related decline.KEY MESSAGESTelomere length (TL) is a potential biomarker and cause of aging, however, the causal relationship between TL and aging-related traits has not been thoroughly examined using a Mendelian randomization (MR) approach.We evaluated genetically increased TL (GI-TL) and its association with over 50 aging-related traits in the UK Biobank cohort using regression models and MR approaches.Pulmonary function (FEV1 and FVC) and blood pressure (SBP, DBP, and PP) traits were positively associated with GI-TL in the expected and unexpected direction, respectively.Using inverse probability weights to account for the non-representativeness of the UKB, our observed associations for GI-TL with blood pressure traits and pulmonary function persisted.Using simulated data to examine study selection as a potential source of collider bias, we concluded that selection bias was unlikely to explain the observed associations.

scholarly journals Telomeres and Telomere Length: A General Overview

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 558 ◽  
Author(s):  
Nalini Srinivas ◽  
Sivaramakrishna Rachakonda ◽  
Rajiv Kumar
Keyword(s):  
Environmental Factors ◽  
Telomere Length ◽  
Replicative Senescence ◽  
Association Studies ◽  
Epidemiological Data ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Telomere Attrition ◽  
Age Related ◽  
The Impact

Telomeres are highly conserved tandem nucleotide repeats that include proximal double-stranded and distal single-stranded regions that in complex with shelterin proteins afford protection at chromosomal ends to maintain genomic integrity. Due to the inherent limitations of DNA replication and telomerase suppression in most somatic cells, telomeres undergo age-dependent incremental attrition. Short or dysfunctional telomeres are recognized as DNA double-stranded breaks, triggering cells to undergo replicative senescence. Telomere shortening, therefore, acts as a counting mechanism that drives replicative senescence by limiting the mitotic potential of cells. Telomere length, a complex hereditary trait, is associated with aging and age-related diseases. Epidemiological data, in general, support an association with varying magnitudes between constitutive telomere length and several disorders, including cancers. Telomere attrition is also influenced by oxidative damage and replicative stress caused by genetic, epigenetic, and environmental factors. Several single nucleotide polymorphisms at different loci, identified through genome-wide association studies, influence inter-individual variation in telomere length. In addition to genetic factors, environmental factors also influence telomere length during growth and development. Telomeres hold potential as biomarkers that reflect the genetic predisposition together with the impact of environmental conditions and as targets for anti-cancer therapies.

scholarly journals Inflamm-Aging Is Associated with Lower Plasma PTX3 Concentrations and an Impaired Capacity of PBMCs to Express hTERT following LPS Stimulation

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Aaron L. Slusher ◽  
Tiffany M. Zúñiga ◽  
Edmund O. Acevedo
Keyword(s):  
Gene Expression ◽  
Young Adults ◽  
Telomere Length ◽  
Immune Cell ◽  
Ex Vivo ◽  
Middle Aged ◽  
Human Telomerase Reverse Transcriptase ◽  
Negatively Associated ◽  
Htert Gene ◽  
Age Related

Age-related elevations in proinflammatory cytokines, known as inflamm-aging, are associated with shorter immune cell telomere lengths. Purpose. This study examined the relationship of plasma PTX3 concentrations, a biomarker of appropriate immune function, with telomere length in 15 middle-aged (40-64 years) and 15 young adults (20-31 years). In addition, PBMCs were isolated from middle-aged and young adults to examine their capacity to express a key mechanistic component of telomere length maintenance, human telomerase reverse transcriptase (hTERT), following ex vivo cellular stimulation. Methods. Plasma PTX3 and inflammatory cytokines (i.e., IL-6, IL-10, TGF-β, and TNF-α), PBMC telomere lengths, and PBMC hTERT gene expression and inflammatory protein secretion following exposure to LPS, PTX3, and PTX3+LPS were measured. Results. Aging was accompanied by the accumulation of centrally located visceral adipose tissue, without changes in body weight and BMI, and alterations in the systemic inflammatory milieu (decreased plasma PTX3 and TGF-β; increased TNF-α (p≤0.050)). In addition, shorter telomere lengths in middle-aged compared to young adults (p=0.011) were negatively associated with age, body fat percentages, and plasma TNF-α (r=−0.404, p=0.027; r=−0.427, p=0.019; and r=−0.323, p=0.041, respectively). Finally, the capacity of PBMCs to increase hTERT gene expression following ex vivo stimulation was impaired in middle-aged compared to young adults (p=0.033) and negatively associated with telomere lengths (r=0.353, p=0.028). Conclusions. Proinflammation and the impaired hTERT gene expression capacity of PBMCs may contribute to age-related telomere attrition and disease.

scholarly journals Childhood Cognition and Age-Related Change in Standing Balance Performance From Mid to Later Life: Findings From a British Birth Cohort

2018 ◽  
Vol 75 (1) ◽  
pp. 155-161 ◽  
Author(s):  
Joanna M Blodgett ◽  
Diana Kuh ◽  
Rebecca Hardy ◽  
Daniel H J Davis ◽  
Rachel Cooper
Keyword(s):  
Cognitive Processing ◽  
Verbal Memory ◽  
Repeated Measures ◽  
Later Life ◽  
Standing Balance ◽  
Balance Performance ◽  
Standard Deviation Increase ◽  
Eyes Closed ◽  
Age Related ◽  
The Impact

Abstract Background Cognitive processing plays a crucial role in the integration of sensory input and motor output that facilitates balance. However, whether balance ability in adulthood is influenced by cognitive pathways established in childhood is unclear, especially as no study has examined if these relationships change with age. We aimed to investigate associations between childhood cognition and age-related change in standing balance between mid and later life. Methods Data on 2,380 participants from the MRC National Survey of Health and Development were included in analyses. Repeated measures multilevel models estimated the association between childhood cognition, assessed at age 15, and log-transformed balance time, assessed at ages 53, 60–64, and 69 using the one-legged stand with eyes closed. Adjustments were made for sex, death, attrition, anthropometric measures, health conditions, health behaviors, education, other indicators of socioeconomic position (SEP), and adult verbal memory. Results In a sex-adjusted model, 1 standard deviation increase in childhood cognition was associated with a 13% (95% confidence interval: 10, 16; p &lt; .001) increase in balance time at age 53, and this association got smaller with age (cognition × age interaction: p &lt; .001). Adjustments for education, adult verbal memory, and SEP largely explained these associations. Conclusions Higher childhood cognition was associated with better balance performance in midlife, with diminishing associations with increasing age. The impact of adjustment for education, cognition and other indicators of SEP suggested a common pathway through which cognition is associated with balance across life. Further research is needed to understand underlying mechanisms, which may have important implications for falls risk and maintenance of physical capability.

Effects of Qigong on Blood Pressure, Blood Pressure Determinants and Ventilatory Function in Middle-Aged Patients with Essential Hypertension

2003 ◽  
Vol 31 (03) ◽  
pp. 489-497 ◽  
Author(s):  
Myung Suk Lee ◽  
Myeong Soo Lee ◽  
Euy-Soon Choi ◽  
Hun-Taeg Chung
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Vital Capacity ◽  
Forced Expiratory Volume ◽  
Control Group ◽  
Middle Aged ◽  
Aged Patients ◽  
Urinary Catecholamines ◽  
Baseline Values ◽  
Sympathetic Nervous

This study was designed to measure changes in blood pressure (BP), urinary catecholamines and ventilatory functions of patients with mild essential hypertension after 10 weeks of Qigong (Shuxinpingxuegong). Fifty-eight patients volunteered to participate in this study and were randomly divided into either a Qigong group (n = 29), or a control group (n = 29). Systolic blood pressure and diastolic blood pressure decreased significantly in the Qigong group such that both became significantly lower after 10 weeks in the Qigong than in the control group. Also, there was a significant reduction of norepinephrine, metanephrine and epinephrine compared to baseline values in the Qigong group. The ventilatory functions, forced vital capacity and forced expiratory volume per sec, were increased in the Qigong group but not the control. These results suggest that Qigong may stabilize the sympathetic nervous system is effective in modulating levels of urinary catecholamines and BP positively, and in improving ventilatory functions in mildly hypertensive middle-aged patients.

scholarly journals Effects of β-adrenergic receptor agonists on drinking and arterial blood pressure in young and old rats

2011 ◽  
Vol 300 (4) ◽  
pp. R1001-R1008 ◽  
Author(s):  
Robert L. Thunhorst ◽  
Connie L. Grobe ◽  
Terry G. Beltz ◽  
Alan Kim Johnson
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Aged Rats ◽  
Middle Aged ◽  
Young Rats ◽  
Arterial Blood ◽  
Age Related ◽  
Old Rats

These experiments examined water-drinking and arterial blood pressure responses to β-adrenergic receptor activation in young (4 mo), “middle-aged” adult (12 mo), and old (29 mo) male rats of the Brown-Norway strain. We used isoproterenol to simultaneously activate β1- and β2-adrenergic receptors, salbutamol to selectively activate β2-adrenergic receptors, and the combination of isoproterenol and the β2-adrenergic receptor antagonist ICI 118,551 to stimulate only β1-adrenergic receptors. Animals received one of the drug treatments, and water drinking was measured for 90 min. About 1 wk later, animals received the same drug treatment for measurement of arterial blood pressure responses for 90 min. In some rats, levels of renin and aldosterone secretion in response to isoproterenol or salbutamol were measured in additional tests. Old and middle-aged rats drank significantly less after isoproterenol than did young rats and also had greater reductions in arterial blood pressure. Old and middle-aged rats drank significantly less after salbutamol than did young rats, although reductions in arterial blood pressure were equivalent across the ages. The β2-adrenergic antagonist ICI 118,551 abolished drinking after isoproterenol and prevented most of the observed hypotension. Renin secretion after isoproterenol and salbutamol was greater in young rats than in middle-aged rats, and wholly absent in old rats. Aldosterone secretion was reduced in old rats compared with young and middle-aged rats after treatment with isoproterenol, but not after treatment with salbutamol. In conclusion, there are age-related differences in β-adrenergic receptor-mediated drinking that can be explained only in part by age-related differences in renin secretion after β-adrenergic receptor stimulation.

scholarly journals Adiposity and insulin resistance correlate with telomere length in middle-aged Arabs: the influence of circulating adiponectin

2010 ◽  
Vol 163 (4) ◽  
pp. 601-607 ◽  
Author(s):  
Omar S Al-Attas ◽  
Nasser M Al-Daghri ◽  
Majed S Alokail ◽  
Assim Alfadda ◽  
Ahmed Bamakhramah ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Telomere Length ◽  
Serum Insulin ◽  
Accelerated Aging ◽  
Model Assessment ◽  
Protective Effects ◽  
Ang Ii ◽  
Middle Aged

ObjectiveStudies in obesity have implicated adipocytokines in the development of insulin resistance, which in turn may lead to accelerated aging. In this study, we determined associations of chromosomal telomere length (TL) to markers of obesity and insulin resistance in middle-aged adult male and female Arabs with and without diabetes mellitus type 2 (DMT2).Design and methodsOne hundred and ninety-three non-diabetic and DMT2 subjects without complications (97 males and 96 females) participated in this cross-sectional study. Clinical data, as well as fasting blood samples, were collected. Serum glucose and lipid profile were determined using routine laboratory methods. Serum insulin, leptin, adiponectin, resistin, tumor necrosis factor-α, and PAI-1 were quantified using customized multiplex assay kits. High sensitive C-reactive protein (hsCRP) and angiotensin II (ANG II) were measured using ELISAs. Circulating leukocyte TL was examined by quantitative real-time PCR.ResultsCirculating chromosomal leukocyte TL had significant inverse associations with body mass index (BMI), systolic blood pressure, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein (LDL)- and total cholesterol, ANG II and hsCRP levels. Adiponectin, BMI, systolic blood pressure, and LDL cholesterol predicted 47% of the variance in TL (P<0.0001). HOMA-IR was the most significant predictor for TL in males, explaining 35% of the variance (P=0.01). In females, adiponectin accounted for 28% of the variance in TL (P=0.01).ConclusionObesity and insulin resistance are associated with chromosomal TL among adult Arabs. Evidence of causal relations needs further investigation. The positive association of adiponectin to TL has clinical implications as to the possible protective effects of this hormone from accelerated aging.

scholarly journals Age-Related Differences in Experiences With Social Distancing at the Onset of the COVID-19 Pandemic: A Computational and Content Analytic Investigation of Natural Language From a Social Media Survey (Preprint)

2020 ◽  
Author(s):  
Ryan C Moore ◽  
Angela Y Lee ◽  
Jeffrey T Hancock ◽  
Meghan C Halley ◽  
Eleni Linos
Keyword(s):  
Public Health ◽  
Age Groups ◽  
Prevention Measures ◽  
Middle Aged ◽  
Social Distancing ◽  
Aged People ◽  
Age Related ◽  
Health Related ◽  
The Impact ◽  
Health Guidance

BACKGROUND As COVID-19 poses different levels of threat to people of different ages, health communication regarding prevention measures such as social distancing and isolation may be strengthened by understanding the unique experiences of various age groups. OBJECTIVE The aim of this study was to examine how people of different ages (1) experienced the impact of the COVID-19 pandemic and (2) their respective rates and reasons for compliance or noncompliance with social distancing and isolation health guidance. METHODS We fielded a survey on social media early in the pandemic to examine the emotional impact of COVID-19 and individuals’ rates and reasons for noncompliance with public health guidance, using computational and content analytic methods of linguistic analysis. RESULTS A total of 17,287 participants were surveyed. The majority (n=13,183, 76.3%) were from the United States. Younger (18-31 years), middle-aged (32-44 years and 45-64 years), and older (≥65 years) individuals significantly varied in how they described the impact of COVID-19 on their lives, including their emotional experience, self-focused attention, and topical concerns. Younger individuals were more emotionally negative and self-focused, while middle-aged people were other-focused and concerned with family. The oldest and most at-risk group was most concerned with health-related terms but were lower in anxiety (use of fewer anxiety-related terms) and higher in the use of emotionally positive terms than the other less at-risk age groups. While all groups discussed topics such as acquiring essential supplies, they differentially experienced the impact of school closures and limited social interactions. We also found relatively high rates of noncompliance with COVID-19 prevention measures, such as social distancing and self-isolation, with younger people being more likely to be noncompliant than older people (<i>P</i>&lt;.001). Among the 43.1% (n=7456) of respondents who did not fully comply with health orders, people differed substantially in the reasons they gave for noncompliance. The most common reason for noncompliance was not being able to afford to miss work (n=4273, 57.3%). While work obligations proved challenging for participants across ages, younger people struggled more to find adequate space to self-isolate and manage their mental and physical health; middle-aged people had more concerns regarding childcare; and older people perceived themselves as being able to take sufficient precautions. CONCLUSIONS Analysis of natural language can provide insight into rapidly developing public health challenges like the COVID-19 pandemic, uncovering individual differences in emotional experiences and health-related behaviors. In this case, our analyses revealed significant differences between different age groups in feelings about and responses to public health orders aimed to mitigate the spread of COVID-19. To improve public compliance with health orders as the pandemic continues, health communication strategies could be made more effective by being tailored to these age-related differences.

scholarly journals Oral Intake of EPA:DHA 6:1 by Middle-Aged Rats for One Week Improves Age-Related Endothelial Dysfunction in Both the Femoral Artery and Vein: Role of Cyclooxygenases

2020 ◽  
Vol 21 (3) ◽  
pp. 920 ◽  
Author(s):  
Sébastien Gaertner ◽  
Cyril Auger ◽  
Muhammad A. Farooq ◽  
Brigitte Pollet ◽  
Sonia Khemais-Benkhiat ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Femoral Artery ◽  
Contractile Response ◽  
Corn Oil ◽  
Femoral Vein ◽  
Middle Aged ◽  
Partial Relaxation ◽  
Age Related ◽  
Increased Risk ◽  
The Impact

In humans, aging is associated with endothelial dysfunction and an increased risk of venous thromboembolism. Although intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a ratio of 6:1 by old rats improved the endothelial dysfunction in arteries, the impact on veins remains unclear. Eight-month-old male Wistar rats were either untreated or orally administered corn oil, EPA:DHA 1:1, or EPA:DHA 6:1 (500 mg/kg/d) for seven days. Vascular reactivity was studied by myography. In middle-aged femoral artery rings, acetylcholine caused a partial relaxation at low concentrations and a contractile response at high concentrations, whereas in the old femoral vein only a partial relaxation was observed. The EPA:DHA 6:1 treatment blunted the contractile response to acetylcholine in the middle-aged femoral artery and both EPA:DHA 6:1 and 1:1 increased the relaxation to acetylcholine in the old femoral vein. No such effects were observed with corn oil. Both the non-selective cyclooxygenase inhibitor indomethacin and the COX-1 inhibitor SC-560 increased the relaxation to acetylcholine in the middle-aged femoral artery whereas the COX-2 inhibitor NS-398 increased that in the middle-aged femoral vein. In conclusion, our results indicate that aging is associated with an endothelial dysfunction in the femoral artery and vein, which can be improved by EPA:DHA 6:1 treatment—most likely via a cyclooxygenase-dependent mechanism.

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