Telomere Length Measurement Research Articles

Genetically Determined Telomere Length Is Associated with Pancreatic Neuroendocrine Neoplasms Onset

Introduction: Telomere length (TL) is a potential indicator of cancer predisposition; however, the multitude of techniques used to measure it causes the results to be heterogeneous and, in some cases, controversial. In the last years, several studies adopted a strategy based on TL-associated genetic variants to generate a polygenic score, often referred as teloscore, used in lieu of direct TL measurement. For pancreatic neuroendocrine neoplasms (PanNEN), this strategy has not been attempted yet. Methods: A teloscore was generated using 11 SNPs (NAF1-rs7675998, ZNF676-rs409627, TERC-rs10936599, CTC1-rs3027234, PXK-rs6772228, DHX35-rs6028466, OBFC1-rs9420907, ZNF208-rs8105767, ACYP2-rs11125529, TERT-rs2736100, and ZBTB46-rs755017), and 291 PanNEN cases and 1,686 controls collected by the PANcreatic Disease ReseArch (PANDoRA) consortium were genotyped to analyse the association of the teloscore and its individual SNPs with the risk of developing PanNEN. Results: An association between genetically determined long telomeres and the risk of developing PanNEN (OR = 1.99, CI: 1.33–2.98, p = 0.0008) for highest versus median (third) quintile was observed. In addition, two novel SNPs associated with PanNEN risk were identified: ZNF676-rs409627 (OR_{C/C_vs_G/G} = 2.27, CI: 1.58–3.27, p = 8.80 × 10⁻⁶) and TERT-rs2736100 (OR_{C/A_vs_C/C} = 2.03, CI: 1.42–2.91, p = 1.06 × 10⁻⁴). Conclusion: In conclusion, this study provides for the first time a clear indication of the association between long genetically determined telomeres and increased risk of developing PanNEN.

The Length of Leukocyte and Femoral Artery Telomeres in Patients with Peripheral Atherosclerosis.

The length of telomeres (TLs) that protect chromosome ends may reflect the age of cells as well as the degree of genetic material damage caused by external factors. Since leukocyte telomere length is associated with cardiovascular diseases, the aim of this study was to evaluate whether leukocyte TL reflects femoral artery wall telomeres of patients with atherosclerosis and lower limb ischemia. Samples of femoral artery wall and blood were collected from 32 patients qualified to surgical revascularization. The analysis included blood and artery wall telomere length measurement and biochemical parameters. The study indicated that there was a moderate correlation between artery wall TL and leukocyte TL. Leukocyte TL was, on average, two times shorter than artery wall TL and correlated with the number of white blood cells. In turn, artery TL was impacted by total cholesterol level. The results suggest that the length of leukocyte telomeres may reflect artery wall TL and indirectly reflect the processes taking place in the artery wall in patients with atherosclerosis.

Systemic Human Htert Aav Gene Transfer Therapy And The Effect On Telomere Length And Biological Age, A Case Report

A single adult female human was treated with AAV hTERT gene transfer therapy on two separate occasions 5 years apart. Follow-up is 5.8 years. The first dose administered on 9.16.2015 consisted of a total intravenous dose of 3e15 AAV hTERT. The second dose administered on 9.24.2020 consisted of a total intravenous dose of 3e15 AAV hTERT. Before and after each therapy and periodically in between the doses, Human Leucocyte telomere analysis was performed. The initial telomere length measurements collected on 9.15.2015 at the initiation of the AAV hTERT gene transfer therapy demonstrated a baseline average telomere length of 6.71kb which corresponded to a telomere percentage relative to age and population at the 30th percentile. The most recent telomere length measurements collected on 7.13.2021 demonstrated an average telomere length of 8.94kb which corresponded to a telomere percentage relative to age and population at the 89th percentile. The results demonstrate the progressive lengthening of the recipient’s telomeres from 6.71kb to 8.94kb despite advancing 5.8 years in chronological age. Associated age as related to telomere length (also known as biological age) was calculated and compared to chronological age. Initially on 9.15.2015, and prior to the first AAV hTERT gene transfer therapy, the associated age was calculated to be 62 years. The latest telomere analysis dated 7.13.2021 demonstrated a calculated associated age of 25 years. This decrease in associated, or biological age, decreased at a rate of 5.3 years per year of chronological age advancement.

Analysis of Telomere Length and Its Implication in Neurocognitive Functions in Elderly Women.

During the normal aging process, a series of events occur, such as a decrease in telomere length and a decrease in various cognitive functions, such as attention, memory, or perceptual-motor speed. Several studies have attempted to establish a correlation between both variables; however, there is considerable controversy in the scientific literature. The aim of our study was to establish a correlation between the scores obtained in the following different cognitive tests: the Mini-Mental State Examination, the Benton Visual Retention Test, the Trail Making Test, the Rey Auditory Verbal Learning Test, the Stroop Test, and the measurement of telomere length. The sample consisted of a total of 41 physically active, healthy women, with a mean age of 71.21 (±4.32) and of 33 physically inactive, healthy women, with a mean age of 72.70 (±4.13). Our results indicate that there is no correlation between the scores obtained by the women in either group and their telomere length. Therefore, it is not possible to conclude that telomere length can be correlated with cognitive performance.

Genomic instability evaluation by BMCyt and telomere length in Brazilian family farmers exposed to pesticides

Brazil is one of the largest consumers of pesticides in the world. This high consumption has resulted in higher potential health risk to agricultural farm workers due to occupational exposure. Hence, the aim of this study is to evaluate genomic instability, using Buccal Micronucleus Cytome (BMCyt) and telomere length (TL) measurement as biomarkers of occupational exposure to pesticides in rural workers living in the State of São Paulo, Brazil. Genomic instability was evaluated in 81 pesticide-exposed farm workers (69 males and 12 females) with a mean age of 49.16 ± 10.06 years and a mean time job of 30.00 ± 14.00 years,81 non-exposed individuals (62 males and 15 females) with a mean age of 47.87 ± 10.66 years. BMCyt results showed significantly higher levels of cell damage (micronuclei and binucleated cells) and cell death (karyorrhectic and condensed chromatin cells) in subjects exposed to pesticide when compared to those non-exposed (p < 0.05). Although our results did not show significant differences in TL among exposed and non-exposed groups, effects in TL due to pesticide exposure was found in a multivariable linear regression model when we stratified the groups by age (≤ 49 years and ≥ 50 years old; β = 11.21, p = 0.006). In addition, TL reduction on was identified in relation to an increase in cigarette pack consumption (β = −0.633, p = 0.045). Furthermore, exposure to specific pesticides presented different effects in TL. Cypermethrin exposure resulted in a reduction in TL (β = −18.039, p = 0.018), while abamectin exposure led to an increase in TL (β = 23.990, p = 0.007). Thus, our findings substantiate genomic instability due to pesticides exposure.

Reduced telomere length in amniocytes: an early biomarker of abnormal fetal development?

Telomeres protect chromosome ends and control cell division and senescence. During organogenesis, telomeres need to be long enough to ensure the cell proliferation necessary at this stage of development. Previous studies have shown that telomere shortening is associated with growth retardation and congenital malformations. However, these studies were performed in newborns or postnatally, and data on telomere length (TL) during the prenatal period are still very limited. We measured TL using quantitative PCR in amniotic fluid (AF) and chorionic villi (CV) samples from 69 control fetuses with normal ultrasound (52 AF and 17 CV) and 213 fetuses (165 AF and 48 CV) with intrauterine growth retardation (IUGR) or congenital malformations diagnosed by ultrasound. The samples were collected by amniocentesis at the gestational age (GA) of 25.0 ± 5.4weeks and by CV biopsy at 18.1 ± 6.3weeks. In neither sample type was TL influenced by GA or fetal sex. In AF, a comparison of abnormal versus normal fetuses showed a significant telomere shortening in cases of IUGR (reduction of 34%, P < 10-6), single (29%, P < 10-6) and multiple (44%, P < 10-6) malformations. Similar TL shortening was also observed in CV from abnormal fetuses but to a lesser extent (25%, P = 0.0002; 18%, P = 0.016; 20%, P = 0.004, respectively). Telomere shortening was more pronounced in cases of multiple congenital anomalies than in fetuses with a single malformation, suggesting a correlation between TL and the severity of fetal phenotype. Thus, TL measurement in fetal samples during pregnancy could provide a novel predictive marker of pathological development.

Race Differences in Telomere Length in Benign Prostate Biopsies and Subsequent Risk of Prostate Cancer.

Telomere shortening is linked to aging and may be associated with increased risk for cancer. Most cancer studies have used telomere length in leukocytes rather than in the target tissue of cancer origin. A case-control study of 524 case-control pairs with a benign prostate biopsy nested within a historical cohort of 10,478 men was conducted to determine whether premalignant prostate telomere length (assessed using a modified qRT-PCR) is associated with prostate cancer risk. Telomere lengths in benign prostate biopsies of cases versus controls were similar (1.46 ± 0.38 vs. 1.45 ± 0.42; P = 0.49). African American (AA) men had significantly shorter telomeres compared with White men (1.51 ± 0.38 vs. 1.63 ± 0.39; P < 0.0001). In race-stratified analyses, increasing telomere length was more strongly associated with prostate cancer risk in White men, wherein those with telomere length in the highest quartile had 1.9-fold greater adjusted risk of prostate cancer compared with men with prostate telomere lengths in the lowest quartile [OR = 1.90; 95% confidence interval (CI) = 1.08-3.36]. Men in the highest telomere length quartile also had a greater risk of aggressive prostate cancer compared with men with telomere lengths in the lowest quartile (OR = 2.78; 95% CI = 1.25-6.19). White men have longer telomeres in benign prostate tissue compared with AA men, and those with the longest telomeres may be at increased risk for prostate cancer, particularly the more aggressive form of the disease. Race-specific telomere length measures may be an early biomarker of aggressive prostate cancer.

Telomere length of the gums of patients with diabetes mellitus in non-alcoholic fatty liver disease

Background: It is known that all pathological conditions in the organs and tissues of the periodontium, especially on the background of metabolic diseases, are accompanied by a reduction in the vital activity of cells, an acceleration of the processes of their aging and death. Measurement of telomere length can become a reliable marker of decreased activity of periodontal cells in patients with diabetes mellitus.

Gender Differences in Perceived Stress and Its Relationship to Telomere Length in Costa Rican Adults

IntroductionStress is associated with disease and reduced leukocyte telomere length (LTL). The objective of this research is to determine if self-perceived stress is associated with telomere length in Costa Rican adults and the gender differences in this association. Findings may help explain how some populations in apparent socioeconomic disadvantage and with limited access to specialized medical services have a remarkably high life expectancy.MethodologyData come from the pre-retirement cohort of the Costa Rican Longevity and Healthy Aging Study (CRELES), a population based survey conducted in the households to 2,327 adults aged 53 to 66 years. The DNA to measure LTL was extracted from blood cells in laboratories of the University of Costa Rica whereas the Blackburn laboratory at the University of California performed the telomere length measurement applying the quantitative polymerase chain reaction (Q-PCR). The relationship between telomere length and perceived stress was measured using least-squares multiple regression. Perceived stress was measured by a set of questions about family, job, finances and, health reasons to be stressed. Models included the control variables: (1) age and sex of the participant, (2) whether he or she resides in the Nicoya area, a “blue zone” known for its high longevity, and (3) the aforementioned sociodemographic, health and lifestyles characteristics.ResultsStress perception and LTL are significantly different by sex. Women perceived higher stress levels than men in almost all aspects studied, except work. Women have significantly longer telomeres. Shorter telomeres are significantly associated with caregiving stress in men and with parental health concerns in women. Counter-intuitive telomere lengthenings were observed among women who feel stressed about caring for family members; and among men who feel stressed due to their family relationships as well as concerns about their own health.DiscussionResults confirm that people with self-perceived stress due to caregiving or health issues have shorter telomeres. The relationship between stress and telomere length differs between men and women. Gender relations exert a strong modifier effect on the relationship between stress and LTL: gender is related to perceived stress, telomere length, and apparently also to the way stress and LTL are related.

Telomerase inhibition on acute myeloid leukemia stem cell induced apoptosis with both intrinsic and extrinsic pathways

AimsAcute Myeloid Leukemia (AML) is an invasive and lethal blood cancer caused by a rare population of Leukemia Stem Cells (LSCs). Telomerase activation is a limitless self-renewal process in LSCs. Apart from telomerase role in telomere lengthening, telomerase (especially hTERT subunit) inhibits intrinsic-, extrinsic-, and p53- mediated apoptosis pathways. In this study, the effect of Telomerase Inhibition (TI) on intrinsic-, extrinsic-, p53-mediated apoptosis, and DNMT3a and TET epigenetic markers in stem (CD34+) and differentiated (CD34−) AML cells is evaluated. Main methodsHigh-purity CD34+ (primary AML and KG-1a) cells were enriched using the Magnetic-Activated Cell Sorting (MACS) system. CD34+ and CD34− (primary AML and KG-1a) cells were treated with BIBR1532 and then, MTT assay, Annexin V/7AAD, Ki-67 assay, Telomere Length (TL) measurement, and transcriptional alterations of p53, hTERT, TET2, DNMT3a were analyzed. Finally, apoptosis-related genes and proteins were studied. Key findingsTI with the IC50 values of 83.5, 33.2, 54.3, and 24.6 μM in CD34+ and CD34− (primary AML and KG-1a) cells significantly inhibited cell proliferation and induced apoptosis. However, TI had no significant effect on TL. The results also suggested TI induced intrinsic-, extrinsic-, and p53-mediated apoptosis. It was shown that the expression levels of DNMT3a and TET2 epigenetic markers were highly increased following TI. SignificanceIn total, it was revealed that TI induced apoptosis through intrinsic, extrinsic, and p53 pathways and increased the expression of DNMT3a and TET2 epigenetic markers.

Telomeres and anthropogenic disturbances in wildlife: Asystematic review and meta-analysis.

Human-driven environmental changes are affecting wildlife across the globe. These challenges do not influence species or populations to the same extent and therefore a comprehensive evaluation of organismal health is needed to determine their ultimate impact. Evidence suggests that telomeres (the terminal chromosomal regions) are sensitive to environmental conditions and have been posited as a surrogate for animal health and fitness. Evaluation of their use in an applied ecological context is still scarce. Here, using information from molecular and occupational biomedical studies, we aim to provide ecologists and evolutionary biologists with an accessible synthesis of the links between human disturbances and telomere length. In addition, we perform a systematic review and meta-analysis on studies measuring telomere length in wild/wild-derived animals facing anthropogenic disturbances. Despite the relatively small number of studies to date, our meta-analysis revealed a significant small negative association between disturbances and telomere length (-0.092 [-0.153, -0.031]; n=28; k=159). Yet, our systematic review suggests that the use of telomeres as a biomarker to understand the anthropogenic impact on wildlife is limited. We propose some research avenues that will help to broadly evaluate their suitability: (i) further causal studies on the link between human disturbances and telomeres; (ii) investigating the organismal implications, in terms of fitness and performance, of a given telomere length in anthropogenically disturbed scenarios; and (iii) better understanding of the underlying mechanisms of telomere dynamics. Future studies in these facets will help to ultimately determine their role as markers of health and fitness in wildlife facing anthropogenic disturbances.

Measurement and initial characterization of leukocyte telomere length in 474,074 participants in UK Biobank.

Leukocyte telomere length (LTL) is a proposed marker of biological age. Here we report the measurement and initial characterization of LTL in 474,074 participants in UK Biobank. We confirm that older age and male sex associate with shorter LTL, with women on average ~7 years younger in 'biological age' than men. Compared to white Europeans, LTL is markedly longer in African and Chinese ancestries. Older paternal age at birth is associated with longer individual LTL. Higher white cell count is associated with shorter LTL, but proportions of white cell subtypes show weaker associations. Age, ethnicity, sex and white cell count explain ~5.5% of LTL variance. Using paired samples from 1,351 participants taken ~5 years apart, we estimate the within-individual variability in LTL and provide a correction factor for this. This resource provides opportunities to investigate determinants and biomedical consequences of variation in LTL.

Long-Term Follow-Up of Newborns with 22q11 Deletion Syndrome and Low TRECs

BackgroundPopulation-based neonatal screening using T-cell receptor excision circles (TRECs) identifies infants with profound T lymphopenia, as seen in cases of severe combined immunodeficiency, and in a subgroup of infants with 22q11 deletion syndrome (22q11DS).PurposeTo investigate the long-term prognostic value of low levels of TRECs in newborns with 22q11DS.MethodsSubjects with 22q11DS and low TRECs at birth (22q11Low, N=10), matched subjects with 22q11DS and normal TRECs (22q11Normal, N=10), and matched healthy controls (HC, N=10) were identified. At follow-up (median age 16 years), clinical and immunological characterizations, covering lymphocyte subsets, immunoglobulins, TRECs, T-cell receptor repertoires, and relative telomere length (RTL) measurements were performed.ResultsAt follow-up, the 22q11Low group had lower numbers of naïve T-helper cells, naïve T-regulatory cells, naïve cytotoxic T cells, and persistently lower TRECs compared to healthy controls. Receptor repertoires showed skewed V-gene usage for naïve T-helper cells, whereas for naïve cytotoxic T cells, shorter RTL and a trend towards higher clonality were found. Multivariate discriminant analysis revealed a clear distinction between the three groups and a skewing towards Th17 differentiation of T-helper cells, particularly in the 22q11Low individuals. Perturbations of B-cell subsets were found in both the 22q11Low and 22q11Normal group compared to the HC group, with larger proportions of naïve B cells and lower levels of memory B cells, including switched memory B cells.ConclusionsThis long-term follow-up study shows that 22q11Low individuals have persistent immunologic aberrations and increased risk for immune dysregulation, indicating the necessity of lifelong monitoring.Clinical ImplicationsThis study elucidates the natural history of childhood immune function in newborns with 22q11DS and low TRECs, which may facilitate the development of programs for long-term monitoring and therapeutic choices.

Comparing qPCR and DNA methylation-based measurements of telomere length in a high-risk pediatric cohort.

Various approaches exist to assess population differences in biological aging. Telomere length (TL) is one such measure, and is associated with disease, disability and early mortality. Yet, issues surrounding precision and reproducibility are a concern for TL measurement. An alternative method to estimate TL using DNA methylation (DNAmTL) was recently developed. Although DNAmTL has been characterized in adult and elderly cohorts, its utility in pediatric populations remains unknown. We examined the comparability of leukocyte TL measurements generated using qPCR (absolute TL; aTL) to those estimated using DNAmTL in a high-risk pediatric cohort (N = 269; age: 8–13 years, 83% investigated for maltreatment). aTL and DNAmTL measurements were correlated with one another (r = 0.20, p = 0.001), but exhibited poor measurement agreement and were significantly different in paired-sample t-tests (Cohen’s d = 0.77, p < 0.001). Shorter DNAmTL was associated with older age (r = −0.25, p < 0.001), male sex (β = −0.27, p = 0.029), and White race (β = −0.74, p = 0.008). By contrast, aTL was less strongly associated with age (r = −0.13, p = 0.040), was longer in males (β = 0.31, p = 0.012), and was not associated with race (p = 0.820). These findings highlight strengths and limitations of high-throughput measures of TL; although DNAmTL replicated hypothesized associations, aTL measurements were positively skewed and did not replicate associations with external validity measures. These results also extend previous research in adults and suggest that DNAmTL is a sensitive TL measure for use in pediatric populations.

Telogator: a method for reporting chromosome-specific telomere lengths from long reads.

Telomeres are the repetitive sequences found at the ends of eukaryotic chromosomes and are often thought of as a 'biological clock,' with their average length shortening during division in most cells. In addition to their association with senescence, abnormal telomere lengths are well known to be associated with multiple cancers, short telomere syndromes and as risk factors for a broad range of diseases. While a majority of methods for measuring telomere length will report average lengths across all chromosomes, it is known that aberrations in specific chromosome arms are biomarkers for certain diseases. Due to their repetitive nature, characterizing telomeres at this resolution is prohibitive for short read sequencing approaches, and is challenging still even with longer reads. We present Telogator: a method for reporting chromosome-specific telomere length from long read sequencing data. We demonstrate Telogator's sensitivity in detecting chromosome-specific telomere length in simulated data across a range of read lengths and error rates. Telogator is then applied to 10 germline samples, yielding a high correlation with short read methods in reporting average telomere length. In addition, we investigate common subtelomere rearrangements and identify the minimum read length required to anchor telomere/subtelomere boundaries in samples with these haplotypes. Telogator is written in Python3 and is available at github.com/zstephens/telogator. Supplementary data are available at Bioinformatics online.

A standalone approach to utilize telomere length measurement as a surveillance tool in oral leukoplakia.

Oral squamous cell carcinoma (OSCC) is often preceded by a white patch on a surface of the mouth, called oral leukoplakia (OL). As accelerated telomere length (TL) shortening in dividing epithelial cells may lead to oncogenic transformation, telomere length measurement could serve as a predictive biomarker in OL. However, due to high variability and lack of a universal reference, there has been a limited translational application. Here, we describe an approach of evaluating TL using paired peripheral blood mononuclear cells (PBMC) as an internal reference and demonstrate its translational relevance. Oral brush biopsy and paired venous blood were collected from 50 male OL patients and 44 male healthy controls (HC). Relative TL was measured by quantitative PCR. TL of each OL or healthy sample was normalized to the paired PBMC sample (TL ratio). In OL patients, the mean TL ratio was significantly smaller not only in the patch but also in distal normal oral tissue, relative to healthy controls without a high‐risk oral habit. Dysplasia was frequently associated with a subgroup that showed a normal TL ratio at the patch but significantly smaller TL ratio at a paired normal distal site. Our data suggest that evaluation of TL attrition using a paired PBMC sample eliminates the requirement of external reference DNA, makes data universally comparable and provides a useful marker to define high‐risk OL groups for follow‐up programs. Larger studies will further validate the approach and its broader application in other premalignant conditions.

Prenatal PM2.5 Exposure in Relation to Maternal and Newborn Telomere Length at Delivery.

Particulate matter with an aerodynamic diameter of 2.5 μm or less (PM2.5) is a ubiquitous air pollutant that is increasingly threatening the health of adults and children worldwide. One health impact of elevated PM2.5 exposure is alterations in telomere length (TL)—protective caps on chromosome ends that shorten with each cell division. Few analyses involve prenatal PM2.5 exposure, and paired maternal and cord TL measurements. Here, we analyzed the association between average and trimester-specific prenatal PM2.5 exposure, and maternal and newborn relative leukocyte TL measured at birth among 193 mothers and their newborns enrolled in a New-York-City-based birth cohort. Results indicated an overall negative relationship between prenatal PM2.5 and maternal TL at delivery, with a significant association observed in the second trimester (β = −0.039, 95% CI: −0.074, −0.003). PM2.5 exposure in trimester two was also inversely related to cord TL; however, this result did not reach statistical significance (β = −0.037, 95% CI: −0.114, 0.039), and no clear pattern emerged between PM2.5 and cord TL across the different exposure periods. Our analysis contributes to a limited body of research on ambient air pollution and human telomeres, and emphasizes the need for continued investigation into how PM2.5 exposure during pregnancy influences maternal and newborn health.

Dužina telomera kao biomarker starenja i bolesti

As research related to healthspan and lifespan has become a hot topic, the necessity for a reliable and practical biomarker of aging (BoA), which can provide information about mortality and morbidity risk, along with remaining life expectancy, has increased. The chromosome terminus non-coding protective structure that prevents genomic instability is called a telomere. The continual shortening of telomeres, which affects their structure as well as function, is a hallmark of agedness. The aforementioned process is a potential cause of age-related diseases (ARDs), leading to a bad prognosis and a low survival rate, which compromise health and longevity. Hence, studies scrutinizing the BoAs often include telomere length (TL) as a prospective candidate. The results of these studies suggest that TL measurement can only provide an approximate appraisal of the aging rate, and its implementation into clinical practice and routine use as a BoA has many limitations and challenges. Nevertheless, measuring TL while determining other biomarkers can be used to assess biological age. This review focuses on the importance of telomeres in health, senescence, and diseases, as well as on summarizing the results and conclusions of previous studies evaluating TL as a potential BoA.

Association of telomere length with diabetes mellitus and idiopathic dilated cardiomyopathy in a South Indian population: A pilot study

Telomere shortening has been associated with ageing and with many age-related diseases including cancer, coronary artery disease, heart failure and diabetes. We sought to investigate the link between telomere shortening and age-related diseases like type 2 diabetes mellitus (DM) (without any complications: DM; with neuropathic complication: DN) and idiopathic dilated cardiomyopathy (IDCM) in south Indian population. We compared telomere lengths of blood lymphocytes taken from patients with associated age-related diseases, namely DM (n = 47), DN (n = 52) and IDCM (n = 34) and controls (n = 46). In addition, we evaluated the relationship between echocardiographic left ventricular ejection fraction (LVEF), left ventricular end diastolic and systolic diameters (LVEDd and LVESd) and telomere length in IDCM patients. Telomere length negatively correlated with age in the cohorts with diabetes and IDCM, and in controls. Average telomere length in diabetes and IDCM patients was significantly shorter than that of controls either before or after adjustments for age and sex. Duration of diabetes in patients with type 2 diabetes did not correlate with telomere length. No correlation was found between the length of telomeres and echocardiography parameters like LVEF, LVEDd and LVESd in IDCM patients. Though echocardiographic characteristics of IDCM did not correlate with telomere length, telomere shortening was found to be accelerated in diabetes (both DM and DN) and IDCM in a south Indian population. Neuropathic complication in diabetes had no effect on telomere shortening. While telomere shortening is a cause or a consequence of diabetic and cardiac pathology remains further investigation, the current study substantiates the usefulness of telomere length measurements as a marker in conjunction with other biochemical markers of age-related diseases.

Telomere dynamics in the first year of life, but not later in life, predict lifespan in a wild bird.

Telomeres are protective, nucleoprotein structures at the end of chromosomes that have been associated with lifespan across taxa. However, the extent to which these associations can be attributed to absolute length vs. the rate of telomere shortening prior to sampling remains unresolved. In a longitudinal study, we examined the relationship between lifespan, telomere length and the rate of telomere shortening in wild, purple-crowned fairy-wrens (Malurus coronatus coronatus). To this end, we measured telomere length using quantitative polymerase chain reaction in the blood of 59 individuals sampled as nestlings and 4-14months thereafter, and in 141known-age individuals sampled on average three times across adulthood. We applied within-subject centring analyses to simultaneously test for associations between lifespan and average telomere length and telomere shortening. We reveal that the rate of telomere shortening and to a lesser extent telomere length in the first year of life independently predicted lifespan, with individuals with faster shortening rates and/or shorter telomeres living less long. In contrast, in adulthood neither telomere shortening nor telomere length predicted lifespan, despite a considerably larger data set. Our results suggest that telomere length measured very early in life (during development) and longitudinal assessments of telomere shortening during the first year of life constitute more useful biomarkers of total life expectancy than either telomere length measured after development, or telomere shortening later in adulthood.