Age-independent telomere length predicts fitness in two bird species

Telomeres are dynamic DNA-protein structures that form protective caps at the ends of eukaryotic chromosomes. Although initial telomere length is partly genetically determined, subsequent accelerated telomere shortening has been linked to elevated levels of oxidative stress. Recent studies show that short telomere length alone is insufficient to induce cellular senescence; advanced attrition of these repetitive DNA sequences does, however, reflect ageing processes. Furthermore, telomeres vary widely in length between individuals of the same age, suggesting that individuals differ in their exposure or response to telomere-shortening stress factors. Here, we show that residual telomere length predicts fitness components in two phylogenetically distant bird species: longevity in sand martins, Riparia riparia, and lifetime reproductive success in dunlins, Calidris alpina. Our results therefore imply that individuals with longer than expected telomeres for their age are of higher quality.     

Mid-life leukocyte telomere length and dementia risk: An observational and mendelian randomization study of 435,046 UK Biobank participants

Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data (n = 43,390), we associated TL with brain MRI phenotypes related to AD or vascular dementia pathology. Longer TL was associated with a lower risk of incident AD/ADRD (adjusted Hazard Ratio [aHR] per SD = 0.93, 95% CI 0.90–0.96, p = 3.37 × 10⁻⁷). Longer TL also was associated with better cognitive performance in specific cognitive domains, larger hippocampus volume, lower total volume of white matter hyperintensities, and higher fractional anisotropy and lower mean diffusivity in the fornix. In conclusion, longer TL is inversely associated with AD/ADRD, cognitive impairment, and brain structural lesions toward the development of AD/ADRD. However, the relationships between genetically determined TL and the outcomes above were not statistically significant based on the results from Mendelian randomization analysis results. Our findings add to the literature of prioritizing risk for AD/ADRD. The causality needs to be ascertained in mechanistic studies.     

Telomere length and cardiovascular risk factors in a middle-aged population free of overt cardiovascular disease

Evidence assembled over the last decade shows that average telomere length (TL) acts as a biomarker for biological aging and cardiovascular disease (CVD) in particular. Although essential for a more profound understanding of the underlying mechanisms, little reference information is available on TL. We therefore sought to provide baseline TL information and assess the association of prevalent CVD risk factors with TL in subjects free of overt CVD within a small age range. We measured mean telomere restriction fragment length of peripheral blood leukocytes in a large, representative Asklepios study cohort of 2509 community-dwelling, Caucasian female and male volunteers aged approximately 35-55 years and free of overt CVD. We found a manifest age-dependent telomere attrition, at a significantly faster rate in men as compared to women. No significant associations were established with classical CVD risk factors such as cholesterol status and blood pressure, yet shorter TL was associated with increased levels of several inflammation and oxidative stress markers. Importantly, shorter telomere length was associated with an increasingly unhealthy lifestyle, particularly in men. All findings were age and gender adjusted where appropriate. With these cross-sectional results we show that TL of peripheral blood leukocytes primarily reflects the burden of increased oxidative stress and inflammation, whether or not determined by an increasingly unhealthy lifestyle, while the association with classical CVD risk factors is limited. This further clarifies the added value of TL as a biomarker for biological aging and might improve our understanding of how TL is associated with CVD.     

Nestling telomere length does not predict longevity,but covaries with adult body size in wild barn swallows

Telomere length and dynamics are increasingly scrutinized as ultimate determinants of performance, including age-dependent mortality and fecundity. Few studies have investigated longevity in relation to telomere length (TL) in the wild and none has analysed longevity in relation to TL soon after hatching, despite the fact that telomere shortening may mostly occur early in life. We show that TL in nestling barn swallows (Hirundo rustica) in the wild does not predict longevity. However, TL positively covaries with body size, suggesting that individuals with large TL can afford to grow larger without paying the cost of reduced TL, and/or that benign rearing conditions ensure both large body size and low rates of telomere shortening. Overall, our study hints at a role of TL in developmental processes, but also indicates a need for further analyses to assess the expectation that TL in young individuals predicts longevity in the wild.     

Differential role of Kruppel like factor 1 (KLF1) gene in red blood cell disorders

The master erythroid regulator KLF1,plays a pivotal role during erythroid lineage development by regulating the expression of many erythroid genes. Variations in the KLF1 gene are found to be associated with varied erythroid phenotypes. With the aim of determining the role of KLF1 gene variations in HbF induction and their genotype phenotype relationship, in this study, we screened 370 individuals with different hemoglobinopathy condition. Hematological analysis was carried out using automated blood cell counter and Variant II HPLC (Biorad). KLF1 gene mutations were screened using automated DNA sequencing. Expression analysis was carried out using q-RT PCR of KLF1, BCL11A and γ-globin after selective enrichment and culturing of CD 34 +ve cells into an erythroid lineage. Over all 14 KLF1 gene variations were identified, of which six variants were novel. The incidence of KLF1 gene mutations was found to be 8.1%. It was seen that KLF1 mutations contributed in borderline HbA₂ levels as 7.6% of our borderline HbA₂ cases showed presence of KLF1 variations. It also contributed in induction of HbF levels under stress erythropoietic conditions. Gene expression studies revealed inverse correlation of KLF1, BCL11A (reduced) with γ-globin gene expression (increased) in patients showing KLF1 gene mutations, thus indicating the role of KLF1 gene in regulating the γ-globin gene expression. The identification of genomic variants of the KLF1 may help in determining the functionally active domain of this protein and will facilitate in understanding the wide spectrum of phenotypes generated by these variants.     

A CLCNKA polymorphism (rs10927887; p.Arg83Gly) previously linked to heart failure is associated with the estimated glomerular filtration rate in the RENASTUR cohort

A total of 569 individuals aged 55–85 and Caucasian were genotyped for SNP rs10927887 in the K_a renal chloride channel gene (CLCNKA). The following variables were significantly associated with an estimated glomerular filtration rate of (eGFR) < 60 ml/min./1.73 m²: age, type 2 diabetes, total cholesterol, LDL-cholesterol, and the CLCNKA GG genotype (p = 0.03; OR = 1.65, 95% CI = 1.04–2.62). This novel finding could partly explain the reported greater risk of heart failure linked to the CLCNKA SNP, but requires confirmation on other populations.