Shorter Leukocyte Telomere Length Research Articles

Abstract 4145812: Cardiovascular MRI-Derived Cardiac Age Acceleration is Associated with Shortened Leukocyte Telomere Length But Not Clonal Hematopoiesis of Indeterminate Potential

Introduction: Cardiac structure and function typically decline with age. Abnormal acceleration of this decline, known as cardiac age acceleration, can be estimated from MRI using deep learning. Both general and cardiac-specific mechanisms may contribute to cardiac aging. Longer telomere length in circulating leukocytes, which indicates greater cellular capacity for replication, has been associated with a lower risk of heart failure and more favorable cardiac structure and function Recent data have also suggested that longer telomeres contribute to risk of clonal hematopoiesis of indeterminate potential (CHIP), which has been linked to increased risk of atherosclerosis, heart failure and arrhythmia. Here we studied whether telomere length or CHIP status are associated with deep learning derived cardiac age acceleration. Methods: We developed a deep learning model to estimate cardiac age acceleration in 70,805 UK Biobank participants from the cardiovascular MRI (four-chamber long axis view). Of these, we identified leukocyte telomere length (LTL) in 61,554 and were able to evaluate CHIP in 61,636. In an additional 372,465 participants unrelated to those with imaging, a genome-wide association study (GWAS) was conducted for LTL, and a GWAS of cardiac age acceleration was conducted in those with imaging; using these, a two-sample Mendelian randomization (MR) was performed to identify putatively causal relationships. Results: In the 61,636 participants with both CHIP and cardiac age acceleration measurements, CHIP was not associated with cardiac age acceleration regardless of driver gene (p=0.79). In contrast, cardiac age acceleration was associated with a shorter LTL (Beta=-0.025 SD, p=5.4E-10). Shorter LTL was causally associated with cardiac age acceleration (Beta=-0.10, p=0.047). Conclusions: These data suggest that general aging mechanisms conferred by shortening telomeres may contribute to the age-associated structural and functional decline of the heart as observed with MRI. In comparison, the relationship between CHIP and cardiovascular risk may not manifest in ways that cause apparent cardiac age acceleration.

Telomere length and chronotype among women in the California Teachers Study (CTS)

ABSTRACT While links between certain chronotypes and poorer health outcomes have been well established in previous studies, few studies have examined the relationship between chronotype and cellular aging. Using data from the California Teachers Study (CTS), the present study evaluates the relationship between cellular aging and chronobiology through an analysis of leukocyte telomere length (LTL) and chronotype among 817 predominantly postmenopausal women with no history of cancer and occupations not associated with night-shift work. Unconditional logistic regression models were run to estimate odds ratios (ORs) for each chronotype category, adjusted for age, ethnicity, and smoking status. Analyses were then stratified by potential modifiers to assess whether results varied among specific subgroups within the sample. Women who reported being current evening types and evening types from teen years to now were significantly less likely to have short LTL compared to women who reported being current morning types or morning types from teen years to now (OR = 0.72; 95% CI = 0.53-0.98; OR = 0.57; 95% CI = 0.39-0.84). Our results suggest that women with no history of cancer who identify as evening chronotypes may undergo decreased cellular aging compared to women in the same population who identify as morning types. Further studies on populations of postmenopausal women are warranted.

Association of leukocyte telomere length and the risk of disease severity and metabolic comorbidities in Arab patients with psoriasis.

Several studies have related shortened leukocyte telomere length (LTL) with age-related diseases and worse prognosis. Telomere length attrition has recently been associated with inflammatory diseases, including psoriasis. However, no study has demonstrated an association between LTL and the risk of disease severity and metabolic comorbidities in Arab patients with psoriasis (Ps). 68 Ps and 42 normal controls (NC) were included. LTL and oxidative damage were determined by quantitative (q) PCR. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression. Statistical differences between the groups were determined using 2 and t-tests. Patients with psoriasis had significantly shorter LTL (P= 0.032) and higher oxidative damage (P= 0.015) than those without psoriasis. Patients with moderate-to-severe index (P= 0.03) and metabolic comorbidity showed significantly shorter LTL (P= 0.003) compared to patients with mild index and without metabolic comorbidity, respectively. Patients with short LTL (≤ 0.9) were correlated with higher risk of moderate-to-severe conditions (OR= 6.98, 95% CI= 2.3-20.8, P= 0.001) and metabolic comorbidities (OR= 2.89, 95% CI= 1.02- 8.2, P= 0.04). LTL shortening may be a consequence of increased oxidative damage, and is related to the risk of severe psoriasis and metabolic comorbidities. Therefore, LTL may be a good candidate biomarker for predicting the risk of poor prognosis in patients with psoriasis.

Telomere shortening and cardiac alterations in asymptomatic type 2 diabetes patients: impact of sex

Abstract Background Telomere shortening is associated with the occurrence of deleterious events in the context of cardiometabolic disorders, including type 2 diabetes mellitus (T2DM). However, no evidence is available on the link between leukocyte telomere length (LTL) and subclinical cardiac alterations in T2DM patients. Purpose Our aim is to evaluate the relation between LTL and cardiovascular function in asymptomatic T2DM patients, taking into consideration the impact of the sex. Methods We analyzed a cohort of asymptomatic T2DM patients free from any overt cardiovascular disease (including coronary artery disease) and other T2DM comorbidities. A detailed metabolic and echocardiographic evaluation was performed together with LTL measurements at inclusion and after 2 years of follow-up. Univariate analyses in regard of the comparison of three graded LTL tertiles and different gender were used to test individual relationships betweenbioclinical and echocardiographic parameters and LTL measures. Subsequently, an unsupervised clustering method (self-organizing maps [SOM]) was used to identify cluster at risk of cardiomyopathy. Results We studied 89 T2DM patients aged 50±4 years (43% female) with a mean T2DM duration of 10±5.8 years and an average follow-up of 2.1±0.2 years. Leukocyte TL analysis demonstrated a slight but significant attrition after 2 years. The analysis of echocardiographic variables (transmitral flow velocities, velocity of mitral annular motion, left ventricular ejection fraction) did not show any evidence for ouvert cardiomyopathy. However, in the lower LTL tertile a higher proportion of patients with global longitudinal strain [GLS]<18% was found [41.6% vs. 22.8% vs. 21.6%]. Interestingly, leukocyte TL was associated with T2DM duration, FIB-4, a noninvasive indice used to assess fibrosis associated with non-alcoholic fatty liver disease (NAFLD), and usage of GLP-1 agonists. Comparison of men and women by univariate analysis did not show any differences in both LTL and echocardiographic parameters. However, unsupervised cluster method (SOM) unmasked a subgroup of female T2DM patients with diastolic alterations (e’ mean) and systolic alteration (GLS) both linked with lower LTL, whereas no specific subgroup in male T2DM patients could be distinguished. Conclusion Our study identifies subclinical diastolic and systolic dysfunction together with shorter LTL in a subgroup of female T2DM patients. These findings raise the importance of considering sex effect in the understanding of diabetic cardiomyopathy.

Shorter Leukocyte Telomere Length Is Associated with Increased Major Adverse Cardiovascular Events or Mortality in Patients with Essential Hypertension.

The association between leukocyte telomere length (LTL) alteration and major adverse cardiovascular events (MACE) or mortality in patients with hypertension is still unclear. 20,034 patients with essential hypertension were enrolled from UK biobank. Multivariable COX regression models were performed to assess the association. LTL was shorter in hypertensive patients with MACE compared to those without MACE. Hypertensive patients in the lowest LTL quartile were at higher risk to develop MACE (adjusted HR 1.15 [95%CI 1.02-1.29], vs top LTL quartile, p-trend = 0.03). Similarly, shorter LTL was related with increased mortality (adjusted HR 1.18[95% CI 1.06-1.3], lowest vs top LTL quartile, p-trend < 0.001). This investigation demonstrated that shorter LTL is associated with increased risk of MACE or mortality in patients with essential hypertension, which indicates that LTL may be a potential predictor of prognosis or underlying therapeutic target for hypertension.

Telomere length as a biomarker in multiple sclerosis

Background: Leukocyte telomere length (LTL) shortens with age and may be related to multiple sclerosis (MS). Objective: We hypothesize that chronologically young people with MS (pwMS) with short LTL behave similarly to older MS subjects. Methods: Prospective 2-year study including two cohorts of young (18–35 years) and elderly (⩾50 years) pwMS with similar disease duration. Physical and cognitive evaluation, 3 T brain magnetic resonance imaging (MRI) and retinal nerve fiber layer (RNFL) measurement by optical coherence tomography were performed. LTL was measured by quantitative polymerase chain reaction assay. Results: Around 105 patients were included, 57 young and 48 elderly. LTL was shorter in older patients (0.61 versus 0.57, p = 0.0081) and in males (female, 0.60; male, 0.59; p = 0.01335). For every 10-year increase in age, LTL was 0.02 U shorter. In elderly, LTL correlated with disease duration (p = 0.05), smoking (p = 0.03), Expanded Disability Status Scale (EDSS; p = 0.004), 9HPT (p = 0.00007), high-efficacy therapies (p = 0.001), brain lesion volume (BLV) (p = 0.011), and number of T2 lesions (p = 0.01). In young patients, LTL did not correlate with clinical or radiological variables. For every 0.1 U shorter LTL, gray matter volume decreased 1.75 cm3 and white matter volume 1.78 cm3. Conclusion: LTL correlated with disability and BLV in elderly. Besides LTL shortening, other variables should be considered as mechanisms of neurodegeneration that might be involved in aging pwMS.

Leukocyte telomere length and attrition in association with disease severity in cystic fibrosis patients.

Cystic fibrosis (CF) is characterized by chronic airway inflammation and premature aging. The link with leukocyte telomere length (LTL) as a marker of biological aging is unclear. We studied disease severity and LTL in 168 CF patients of which 85 patients had a second retrospective LTL assessment. A higher FEV1 was associated with longer LTL, with a stronger effect in men (5.08% longer LTL) compared to women (0.41% longer LTL). A higher FEV1/FVC ratio was associated with 7.05% (P=0.017) longer LTL in men. CF asthma, as defined by the treatment with inhaled corticosteroids, was associated with -6.65% shorter LTL (P=0.028). Men homozygous for the ΔF508 genotype showed a -10.48% (P=0.026) shorter LTL compared to heterozygotes. A genotype-specific non-linear association between LTL shortening and chronological age was observed. Stronger age-related LTL shortening was observed in patients homozygous for the ΔF508 genotype (P-interaction= 0.044). This work showed that disease severity in CF patients negatively influences LTL, with slightly more pronounced effects in men. The homozygous genotype for ΔF508 may play a role in LTL attrition in CF patients. Understanding factors in CF patients that accelerate biological aging provides insights into mechanisms that can extend the overall life quality in CF-diseased.

Association and causal impact of TERT genetic variants on peripheral blood leukocyte telomere length and cerebral small vessel disease risk in a Chinese Han population: a mendelian randomization analysis

BackgroundPrevious observational studies have highlighted potential relationships between the telomerase reverse transcriptase (TERT) gene, short leukocyte telomere length (LTL), and cerebrovascular disease. However, it remains to be established as to whether TERT gene variants are associated with an elevated risk of cerebral small vessel disease (CSVD), and whether there is a causal relationship between LTL and CSVD.MethodsFive TERT single nucleotide polymorphisms (SNPs) were analyzed in 307 CSVD patients and 320 healthy controls in whom LTL values were quantified. Allele models and four genetic models were used to explore the relationship between these SNP genotypes and CSVD risk. A Mendelian randomization analysis of CSVD risk was then performed using LTL-related SNPs and the polygenic risk score (PRS) constructed from these SNPs as genetic instrumental variables to predict the causal relationship between LTL and CSVD risk.ResultsModel association analyses identified two SNPs that were significantly associated with CSVD risk. LTL was significantly correlated with age (P < 0.001), and the MR analysis revealed an association between short LTL and an elevated risk of CSVD. PRS-based genetic prediction of short LTLs was also significantly related to an elevated CSVD risk.ConclusionMultiple genetic models and MR results indicate that TERT gene SNPs may be related to an elevated risk of CSVD, and that shorter LTL may be causally linked to such CSVD risk.

Associations of childhood and adulthood body size, and child-to-adult body size change with adult telomere length.

To comprehensivelyexamine the associations of childhood and adulthood body size, and child-to-adult body size change with adult leucocyte telomere length (LTL). We included 453 602 participants from the UK Biobank. Childhood body size at the age of 10 years was collected through a questionnaire. Adulthood body size was assessed using body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fat mass index (FMI), and fat-free mass index (FFMI). Individuals with plumper body size in childhood exhibited shorter LTL in adulthood (-0.0086 [-0.0017, -0.0004]). Adulthood BMI (-0.0286 [-0.0315, -0.0258]), WC (-0.0271 [-0.0303, -0.0238]), WHR (-0.0269 [-0.0308, -0.0230]) and FMI (-0.0396 [-0.0438, -0.0351]) were negatively associated with LTL, whereas FFMI (0.0095 [0.0039, 0.0152]) was positively associated with LTL. Compared to individuals consistently having an average/normal weight in both childhood and adulthood, those who maintained or developed overweight/obesity from childhood to adulthood had a shorter adult LTL, regardless of childhood body size. Notably, the LTL shortening effect was not observed in individuals with plumper body size in childhood but normal weight in adulthood. Childhood and adulthood obesity are both associated with LTL shortening in adulthood. Transitioning to or maintaining overweight/obese status from childhood to adulthood is associated with shorter adult LTL, whereas this effect can be reversed if plumper children become normal weight.

Association between osteoporosis and the rate of telomere shortening.

A shorter leukocyte telomere length (LTL) is reported to be associated with age-related diseases, including osteoporosis. Many studies have tried identifying the association between LTL and osteoporosis, although it remains controversial. This study aimed to determine whether osteoporosis is independently associated with LTL shortening in a prospective longitudinal cohort. The KBASE study is an independent multicenter prospective cohort in South Korea, which began in 2014. We compared the LTL values for each participant at baseline and over a 2-year follow-up period. Boxplots were used to demonstrate the differences in the change in LTL over a 2-year follow-up according to osteoporosis. Multivariable linear regression was conducted to identify whether osteoporosis is independently associated with the rate of telomere shortening. A total of 233 subjects (from 55 to 88 years) from the KBASE cohort were finally enrolled in the study. We observed that the LTL decreased by approximately 1.2 kbp over 2 years. While the LTL decreased as age increased, the rate of LTL shortening did not increase with age. Multivariable linear regression analysis indicated that only osteoporosis was independently associated with rapid LTL shortening over 2 years (B, -8.08; p = 0.038). We sought to identify an association between osteoporosis and LTL shortening in an independent prospective cohort. We found that participants with osteoporosis had significantly faster LTL shortening over 2 years than those without osteoporosis. We hope this study will help elucidate the underlying mechanisms in the relationship between LTL and osteoporosis in the future.

Association of pregnancy complications and postpartum maternal leukocyte telomeres in two diverse cohorts: a nested case-control study

BackgroundBiologic strain such as oxidative stress has been associated with short leukocyte telomere length (LTL), as well as with preeclampsia and spontaneous preterm birth, yet little is known about their relationships with each other. We investigated associations of postpartum maternal LTL with preeclampsia and spontaneous preterm birth.MethodsThis pilot nested case control study included independent cohorts of pregnant people with singleton gestations from two academic institutions: Cohort 1 (hereafter referred to as Suburban) were enrolled prior to 20 weeks’ gestation between 2012 and 2018; and Cohort 2 (hereafter referred to as Urban) were enrolled at delivery between 2000 and 2012. Spontaneous preterm birth or preeclampsia were the selected pregnancy complications and served as cases. Cases were compared with controls from each study cohort of uncomplicated term births. Blood was collected between postpartum day 1 and up to 6 months postpartum and samples were frozen, then simultaneously thawed for analysis. Postpartum LTL was the primary outcome, measured using quantitative polymerase chain reaction (PCR) and compared using linear multivariable regression models adjusting for maternal age. Secondary analyses were done stratified by mode of delivery and self-reported level of stress during pregnancy.Results156 people were included; 66 from the Suburban Cohort and 90 from the Urban Cohort. The Suburban Cohort was predominantly White, Hispanic, higher income and the Urban Cohort was predominantly Black, Haitian, and lower income. We found a trend towards shorter LTLs among people with preeclampsia in the Urban Cohort (6517 versus 6913 bp, p = 0.07), but not in the Suburban Cohort. There were no significant differences in LTLs among people with spontaneous preterm birth compared to term controls in the Suburban Cohort (6044 versus 6144 bp, p = 0.64) or in the Urban Cohort (6717 versus 6913, p = 0.37). No differences were noted by mode of delivery. When stratifying by stress levels in the Urban Cohort, preeclampsia was associated with shorter postpartum LTLs in people with moderate stress levels (p = 0.02).ConclusionOur exploratory results compare postpartum maternal LTLs between cases with preeclampsia or spontaneous preterm birth and controls in two distinct cohorts. These pilot data contribute to emerging literature on LTLs in pregnancy.

Short leukocyte telomere length and high plasma phospholipid fatty acids increase the risk of type 2 diabetes.

In the last 40 years, there has been a notable rise in the occurrence of diabetes within China, leading to the country now having the highest number of individuals affected by this condition globally. This prospective observational study examined the effect of different baseline relative leukocyte telomere length (RTL) and the combined effect of baseline RTL and plasma phospholipid fatty acid (PPFA) on the risk of developing diabetes. Adults from Ningxia Province who underwent baseline and follow-up surveys were included in the study. The correlation between the baseline RTL and PPFA was investigated using a multiple linear regression model. The combined effects of baseline RTL and PPFA levels on the risk of developing type 2 diabetes mellitus (T2DM) were investigated using a Cox regression model with time as the covariate. A total of 1461 study subjects were included in this study. According to the diagnostic criteria of the Chinese Diabetes Society, 141 subjects developed T2DM during the follow-up period. The baseline age was negatively correlated with RTL. After adjustment for age, C16:0, C18:1 n-9, C20:4 n-6, C20:3 n-3, and monounsaturated fatty acid (MUFA) concentrations were negatively correlated with RTL. Multiple linear regression analysis showed that C16:0 and MUFA concentrations influenced RTL. Subjects with shorter RTL at baseline had a higher risk of developing diabetes than those with longer RTL. Subjects with shorter RTL and higher C16:0 and MUFA concentrations at baseline had a higher risk of developing T2DM than those with longer RTL and lower C16:0 and MUFA concentrations. Our findings indicated that PPFA affects changes in RTL. In addition, RTL and PPFA are associated with the occurrence of T2DM.

Telomerase activity, telomere length, and the euploidy rate of human embryos

Background Telomeres maintain chromosome stability, while telomerase counteracts their progressive shortening. Telomere length varies between cell types, with leukocyte telomere length (LTL) decreasing with age. Reduced telomerase activity has been linked to reproductive issues in females, such as low pregnancy rates and premature ovarian failure, with recent studies indicating correlations between telomere length in granulosa cells and IVF outcomes. Objectives The study aims to explore the relationship between telomere length, telomerase activity, and euploid blastocyst rate in infertile women undergoing IVF/ICSI PGT-A cycles. Methods This prospective study involves 108 patients undergoing controlled ovarian stimulation and PGT-A. Telomere length and telomerase activity were measured in peripheral mononuclear cells and granulosa cells (GC), respectively. Results The telomere repeat copy number to single gene copy number ratio (T/S) results respectively 0.6 ± 0.8 in leukocytes and 0.7 ± 0.9 in GC. An inverse relationship was found between LTL and the patient’s age (p < .01). A higher aneuploid rate was noticed in patients with short LTL, with no differences in ovarian reserve markers (p = .15), number of oocytes retrieved (p = .33), and number of MII (p = 0.42). No significant association was noticed between telomere length in GC and patients’ age (p = 0.95), in ovarian reserve markers (p = 0.32), number of oocytes retrieved (p = .58), number of MII (p = .74) and aneuploidy rate (p = .65). Conclusion LTL shows a significant inverse correlation with patient age and higher aneuploidy rates. Telomere length in GCs does not correlate with patient age or reproductive outcomes, indicating differential telomere dynamics between leukocytes and granulosa cells.

Association of retinal image-based, deep learning cardiac BioAge with telomere length and cardiovascular biomarkers.

Our retinal image-based deep learning (DL) cardiac biological age (BioAge) model could facilitate fast, accurate, noninvasive screening for cardiovascular disease (CVD) in novel community settings and thus improve outcome with those with limited access to health care services. This study aimed to determine whether the results issued by our DL cardiac BioAge model are consistent with the known trends of CVD risk and the biomarker leukocyte telomere length (LTL), in a cohort of individuals from the UK Biobank. A cross-sectional cohort study was conducted using those individuals in the UK Biobank who had LTL data. These individuals were divided by sex, ranked by LTL, and then grouped into deciles. The retinal images were then presented to the DL model, and individual's cardiac BioAge was determined. Individuals within each LTL decile were then ranked by cardiac BioAge, and the mean of the CVD risk biomarkers in the top and bottom quartiles was compared. The relationship between an individual's cardiac BioAge, the CVD biomarkers, and LTL was determined using traditional correlation statistics. The DL cardiac BioAge model was able to accurately stratify individuals by the traditional CVD risk biomarkers, and for both males and females, those issued with a cardiac BioAge in the top quartile of their chronological peer group had a significantly higher mean systolic blood pressure, hemoglobin A 1c , and 10-year Pooled Cohort Equation CVD risk scores compared with those individuals in the bottom quartile (p<0.001). Cardiac BioAge was associated with LTL shortening for both males and females (males: -0.22, r2 = 0.04; females: -0.18, r2 = 0.03). In this cross-sectional cohort study, increasing CVD risk whether assessed by traditional biomarkers, CVD risk scoring, or our DL cardiac BioAge, CVD risk model, was inversely related to LTL. At a population level, our data support the growing body of evidence that suggests LTL shortening is a surrogate marker for increasing CVD risk and that this risk can be captured by our novel DL cardiac BioAge model.

Leukocyte Telomere Length Mediates the Associations between Blood Lead and Cadmium with Hypertension among Adults in the United States: A Cross-Sectional Study.

There is evidence to support the links between lead and cadmium exposure with hypertension and also with leukocyte telomere length (LTL). The objective of this study is to investigate the role that LTL may play in the relationship between lead and cadmium exposure and hypertension. This study consisted of 3718 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Logistic regression was used to analyze the relationship between blood metals with hypertension, and the mediating model was used to evaluate the mediating effect of LTL. In the fully adjusted model, both blood lead and cadmium ln-transformed concentrations were significantly positively associated with hypertension risk, as were all quartiles of blood lead. Additionally, we observed positive linear dose-response relationships with hypertension by restricted cubic spline analysis (both p overall < 0.001, p non-linear = 0.3008 for lead and p non-linear = 0.7611 for cadmium). The ln-transformed blood lead and cadmium concentrations were associated with shorter LTL. LTL was inversely related to hypertension and the OR was 0.65 (95% CI: 0.47 to 0.89). Furthermore, LTL had mediating effects on the associations of blood lead and cadmium with hypertension risk, and the mediation proportions were 2.25% and 4.20%, respectively. Our findings suggested that exposure to lead and cadmium raised the risk of hypertension, while LTL played as a mediating factor.

Breaking down causes, consequences, and mediating effects of telomere length variation on human health

BackgroundTelomeres form repeated DNA sequences at the ends of chromosomes, which shorten with each cell division. Yet, factors modulating telomere attrition and the health consequences thereof are not fully understood. To address this, we leveraged data from 326,363 unrelated UK Biobank participants of European ancestry.ResultsUsing linear regression and bidirectional univariable and multivariable Mendelian randomization (MR), we elucidate the relationships between leukocyte telomere length (LTL) and 142 complex traits, including diseases, biomarkers, and lifestyle factors. We confirm that telomeres shorten with age and show a stronger decline in males than in females, with these factors contributing to the majority of the 5.4% of LTL variance explained by the phenome. MR reveals 23 traits modulating LTL. Smoking cessation and high educational attainment associate with longer LTL, while weekly alcohol intake, body mass index, urate levels, and female reproductive events, such as childbirth, associate with shorter LTL. We also identify 24 traits affected by LTL, with risk for cardiovascular, pulmonary, and some autoimmune diseases being increased by short LTL, while longer LTL increased risk for other autoimmune conditions and cancers. Through multivariable MR, we show that LTL may partially mediate the impact of educational attainment, body mass index, and female age at childbirth on proxied lifespan.ConclusionsOur study sheds light on the modulators, consequences, and the mediatory role of telomeres, portraying an intricate relationship between LTL, diseases, lifestyle, and socio-economic factors.

Chronic and Latent Viral Infections and Leukocyte Telomere Length across the Lifespan of Female and Male Individuals Living with or without HIV

Background: Chronic/latent viral infections may accelerate immunological aging, particularly among people living with HIV (PLWH). We characterized chronic/latent virus infections across their lifespan and investigated their associations with leukocyte telomere length (LTL). Methods: Participants enrolled in the CARMA cohort study were randomly selected to include n = 15 for each decade of age between 0 and &gt;60 y, for each sex, and each HIV status. Cytomegalovirus (CMV), Epstein–Barr virus (EBV), human herpesvirus 8 (HHV-8), herpes simplex virus 1 (HSV-1), and HSV-2 infection were determined serologically; HIV, hepatitis C (HCV), and hepatitis B (HBV) were self-reported. LTLs were measured using monochrome multiplex qPCR. Associations between the number of viruses, LTL, and sociodemographic factors were assessed using ordinal logistic and linear regression modeling. Results: The study included 187 PLWH (105 female/82 male) and 190 HIV-negative participants (105 female/84 male), ranging in age from 0.7 to 76.1 years. Living with HIV, being older, and being female were associated with harbouring a greater number of chronic/latent non-HIV viruses. Having more infections was in turn bivariately associated with a shorter LTL. In multivariable analyses, older age, living with HIV, and the female sex remained independently associated with having more infections, while having 3–4 viruses (vs. 0–2) was associated with a shorter LTL. Conclusions: Our results suggest that persistent viral infections are more prevalent in PLWH and females, and that these may contribute to immunological aging. Whether this is associated with comorbidities later in life remains an important question.

Causal association and shared genetics between telomere length and COVID-19 outcomes: New evidence from the latest large-scale summary statistics

BackgroundObservational studies suggested that leukocyte telomere length (LTL) is shortened in COVID-19 patients. However, the genetic association and causality remained unknown. MethodsBased on the genome-wide association of LTL (N = 472,174) and COVID-19 phenotypes (N = 1086,211–2597,856), LDSC and SUPERGNOVA were used to estimate the genetic correlation. Cross-trait GWAS meta-analysis, colocalization, fine-mapping analysis, and transcriptome-wide association study were conducted to explore the shared genetic etiology. Mendelian randomization (MR) was utilized to infer the causality. Upstream and downstream two-step MR was performed to investigate the potential mediating effects. ResultsLDSC identified a significant genetic association between LTL and all COVID-19 phenotypes (rG < 0, p < 0.05). Six significant regions were observed for LTL and COVID-19 susceptibility and hospitalization, respectively. Colocalization analysis found rs144204502, rs34517439, and rs56255908 were shared causal variants between LTL and COVID-19 phenotypes. Numerous biological pathways associated with LTL and COVID-19 outcomes were identified, primarily involving immune-related pathways. MR showed that longer LTL was significantly associated with a lower risk of COVID-19 severity (OR [95% CI] = 0.81 [0.71–0.92], p = 1.24 ×10-3) and suggestively associated with lower risks of COVID-19 susceptibility (OR [95% CI] = 0.96 [0.92–1.00], p = 3.44 ×10-2) and COVID-19 hospitalization (OR [95% CI] = 0.89 [0.80–0.98], p = 1.89 ×10-2). LTL partially mediated the effects of BMI, smoking, and education on COVID-19 outcomes. Furthermore, six proteins partially mediated the causality of LTL on COVID-19 outcomes, including BNDF, QPCT, FAS, MPO, SFTPB, and APOF. ConclusionsOur findings suggested that shorter LTL was genetically associated with a higher risk of COVID-19 phenotypes, with shared genetic etiology and potential causality.

Association Between Ultra-Processed Food Consumption and Leucocyte Telomere Length: A cross-sectional study of UK Biobank

ObjectiveThis study aimed to investigate the association between consumption of ultra-processed foods (UPFs) and leucocyte telomere length (LTL). MethodsThis cross-sectional study utilized data from the UK Biobank, including a total of 64,690 participants. LTL was measured using Q-PCR with natural logarithmic conversion and Z-score normalization. Dietary data were collected through a 24-hour recall questionnaire from 2009 to 2010. UPFs were identified using the Nova food classification and analyzed as either a continuous or categorical variable respectively. Multiple linear regression models were employed to analyze the association between UPF consumption and LTL. ResultsThe included participants had an average age of 56.26 years, of whom 55.2% were female. After adjusting for sociodemographic, lifestyle-related and anthropometric variables, LTL exhibited a decrease of 0.005 (95% CI: −0.007, −0.002) with one UPF serving/day increase. Compared to participants consuming ≤ 3.5 servings/day, those consuming 3.5 to < 6, 6 to ≤ 8 and > 8 servings/day showed a shortening of LTL by 0.025 (95% CI: −0.047, −0.004), 0.034 (95% CI: −0.055, −0.012) and 0.038 (95% CI: −0.062, −0.015), respectively (P for trend = 0.001). Subgroup analyses by UPF subclasses revealed that consumption of ready-to-eat/heated food (β = −0.008, 95% CI: −0.014, −0.002), beans and potatoes (β = −0.024, 95% CI: −0.039, −0.009), animal-based products (β = −0.011, 95% CI: −0.019, −0.004), artificial sugar (β = −0.014, 95% CI: −0.025, −0.004), and beverages (β = −0.005, 95% CI: −0.009, −0.001) showed negative associations with LTL. Conversely, breakfast cereals (β = 0.020, 95% CI: 0.004, 0.036) and vegetarian alternatives (β = 0.057, 95% CI: 0.027, 0.086) showed positive correlations with LTL. ConclusionsOur study found that a higher consumption of total UPFs was associated with a shorter LTL. However, some subclass UPFs may be associated with longer LTL, depending on their nutritional composition.

Association between telomere length and Plasmodium falciparum malaria endemicity in sub-Saharan Africans

Leukocyte telomere length (LTL) varies significantly across human populations, with individuals of African ancestry having longer LTL than non-Africans. However, the genetic and environmental drivers of LTL variation in Africans remain largely unknown. We report here on the relationship between LTL, genetics, and a variety of environmental and climatic factors in ethnically diverse African adults (n= 1,818) originating from Botswana, Tanzania, Ethiopia, and Cameroon. We observe significant variation in LTL among populations, finding that the San hunter-gatherers from Botswana have the longest leukocyte telomeres and that the Fulani pastoralists from Cameroon have the shortest telomeres. Genetic factors explain ∼50% of LTL variation among individuals. Moreover, we observe a significant negative association between Plasmodium falciparum malaria endemicity and LTL while adjusting for age, sex, and genetics. Within Africa, adults from populations indigenous to areas with high malaria exposure have shorter LTL than those in populations indigenous to areas with low malaria exposure. Finally, we explore to what degree the genetic architecture underlying LTL in Africa covaries with malaria exposure.