Biomarker Of Biological Aging Research Articles

Association between shorter leukocyte telomeres and multiple sclerosis

Relative telomere length (TL) is regarded as a biomarker of biological age. Accelerated immune aging, as represented by TL reduction, has been demonstrated in autoimmune diseases, including multiple sclerosis (MS). However, it is still unresolved whether telomere shortening is the cause or the consequence of the pathogenic events underlying autoimmunity.Assessing TL in whole blood DNA samples in 138 MS patients and 120 healthy controls showed reduced TL in patients as compared with controls There seems to be a prelude of accelerated telomere shortening, which may increase the risk for development of MS.

Obesity is associated with shorter telomeres in 8 year-old children

Telomere length is considered a biomarker of biological aging. Shorter telomeres and obesity have both been associated with age-related diseases. To evaluate the association between various indices of obesity with leukocyte telomere length (LTL) in childhood, data from 1,396 mother-child pairs of the multi-centre European birth cohort study HELIX were used. Maternal pre-pregnancy body mass index (BMI) and 4 adiposity markers in children at age 8 (6–11) years were assessed: BMI, fat mass, waist circumference, and skinfold thickness. Relative LTL was obtained. Associations of LTL with each adiposity marker were calculated using linear mixed models with a random cohort effect. For each 1 kg/m² increment in maternal pre-pregnancy BMI, the child’s LTL was 0.23% shorter (95%CI: 0.01,0.46%). Each unit increase in child BMI z-score was associated with 1.21% (95%CI: 0.30,2.11%) shorter LTL. Inverse associations were observed between waist circumference and LTL (−0.96% per z-score unit; 95%CI: −2.06,0.16%), and skinfold thickness and LTL (−0.10% per z-score unit; 95%CI: −0.23,0.02%). In conclusion, this large multicentric study suggests that higher child adiposity indicators are associated with short telomeres in children, and that associations are stronger for child BMI than for maternal pre-pregnancy BMI.

Telomere Maintenance in Pediatric Cancer.

Telomere length has been proposed as a biomarker of biological age and a risk factor for age-related diseases and cancer. Substantial progress has been made in recent decades in understanding the complex molecular relationships in this research field. However, the majority of telomere studies have been conducted in adults. The data on telomere dynamics in pediatric cancers is limited, and interpretation can be challenging, especially in cases where results are contrasting to those in adult entities. This review describes recent advances in the molecular characterization of structure and function of telomeres, regulation of telomerase activity in cancer pathogenesis in general, and highlights the key advances that have expanded our views on telomere biology in pediatric cancer, with special emphasis on the central role of telomere maintenance in neuroblastoma. Furthermore, open questions in the field of telomere maintenance research are discussed in the context of recently published literature.

Shortening telomere is associated with subclinical atherosclerosis biomarker in omnivorous but not in vegetarian healthy men

Telomere length is considered to be a biomarker of biological aging and age-related disease. There are few studies that have evaluated the association between telomere length and diet, and none of them have evaluated the impact of a vegetarian diet on telomere length and its correlation with cardiovascular biomarkers in apparently healthy subjects. Therefore, our objectives were to evaluate leukocyte telomere length (LTL) in vegetarians and omnivorous subjects and its association with classical cardiovascular risk biomarkers. From the total of 745 participants initially recruited, 44 omnivorous and 44 vegetarian men apparently healthy were selected for this study and LTL was measured in 39 omnivorous and 41 vegetarians by Real-Time Quantitative PCR reaction. Although telomere length was not different between omnivorous and vegetarians, we found a strong negative correlation between LTL and IMT (intima-media thickness) in omnivorous, but not in vegetarian group. In addition, omnivorous who were classified with short telomere length had higher carotid IMT compared to vegetarians. Our data suggest that telomere length can be a marker of subclinical atherosclerosis in the omnivorous group.

Association Between Dietary Selenium Intake and Leukocyte Telomere Length in a Nationally Representative Sample of US Adults (OR11-06-19)

ObjectivesDNA damage induced by oxidative stress is implicated in accelerated telomere shortening, a biomarker of biological aging. Although selenium has antioxidant properties, its impact on telomere length is largely unknown. This study aimed to examine the association between dietary selenium intake and leukocyte telomere length in a nationally representative sample of US adults. MethodsWe included 7409 adults aged 20 years or older who participated in the National Health and Nutrition Examination Survey (NHANES) 1999–2002. Dietary selenium intake was calculated using data collected in the 24-hour dietary recall. Leukocyte telomere length was assayed using the quantitative polymerase chain reaction method. The association between selenium intake and telomere length was estimated by weighted linear regression models adjusting for demographic, socioeconomic and lifestyle factors, body mass index, supplements intake, and leukocyte cell type composition. ResultsThe average dietary selenium intake was 109.1 mg/d (standard error [SE] 1.15). We didn’t find a significant association between dietary selenium intake and telomere length in US adults. The average telomere length (SE) was 1.01 (0.02), 1.01 (0.01), and 1.04 (0.01) across increasing tertiles of dietary selenium intake. However, a significant interaction was observed for age (P = 0.02). Among individuals aged 20–44 years, the β coefficient of log-transformed telomere length, compared to lowest tertile of dietary selenium intake, was −0.041 (SE 0.012, P = 0.002) and −0.033 (SE 0.018, P = 0.07) for middle tertile and the highest tertile of selenium intake, respectively. The corresponding β coefficient was 0.009 (SE 0.016, P = 0.59) and −0.001 (SE 0.012, P = 0.95), respectively, for adults 45–64 years old, and 0.017 (SE 0.015, P = 0.28) and 0.059 (SE 0.021, P = 0.01), respectively, for those aged 65 years or older. The results were not appreciably changed even after additionally adjustment for dietary intake of vitamin A, vitamin E, and zinc. ConclusionsThe association between dietary selenium intake and telomere length differed significantly by age groups, indicating that higher selenium intake may prevent telomere shortening in older adults but not in younger or middle-aged adults. Further studies about the underlying mechanisms are warranted. Funding SourcesNA.

Comprehensive N-glycosylation analysis of immunoglobulin G from dried blood spots.

Immunoglobulin G (IgG) glycans are emerging as a new putative biomarker for biological age and different diseases, requiring a robust workflow for IgG glycome analysis, ideally beginning with a simple and undemanding sampling procedure. Here, we report the first comprehensive study on total N-glycans of IgG isolated from dried blood spots (DBSs), which was performed in a high-throughput mode. We compared the IgG N-glycan profiles originating from DBS with those originating from plasma, compared different media for DBS collection, evaluated analytical variation and assessed IgG N-glycan profile stability for different storage conditions. In conclusion, we show that DBSs are a good and stable source material for a robust IgG N-glycan analysis by ultra-performance liquid chromatography, suitable for blood sampling in conditions where no trained personnel and necessary laboratory equipment are available.

Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis.

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life.We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries.The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect.Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.

Can biomarkers of biological age be used to assess cumulative lifetime experience?

AbstractObjective methods for assessing the cumulative lifetime experience of non-human animals would be valuable. We develop the hypothesis that biological age is a common currency that integrates the overall quality of an animal's lifetime experience across a range of types of exposure. Ageing is the result of the accumulation of somatic damage, and its rate is determined by the balance between experiences that cause damage and experiences that mitigate damage or promote repair. Negative affective states are associated with somatic damage via both direct causal and indirect pathways. Based on these premises, we predict that individuals that are biologically old for their chronological age will, on average, have experienced worse lives than individuals that are biologically younger, both in terms of their overall health and affective experience. Biological age is, thus, an attractive measure of cumulative experience because it requires no subjective decisions either about how a given exposure impacts an animal, or about how different dimensions of welfare should be weighted in an overall assessment. Biological age can be measured objectively using biomarkers. We argue that two biomarkers, namely leukocyte telomere length and hippocampal volume, are valid biomarkers of cumulative experience in humans, with potential for use in non-human vertebrates. We discuss how these biomarkers could be used to assess cumulative experience in animals, highlighting some of the limitations. We conclude that biomarkers of biological age offer a viable objective solution to the assessment of cumulative experience and their application in an animal welfare context deserves further exploration.

Association between Body Iron Status and Leukocyte Telomere Length, a Biomarker of Biological Aging, in a Nationally Representative Sample of US Adults

BackgroundExcess iron levels can induce oxidative stress and could therefore affect telomere attrition. However, little is known about the impact of body iron status on telomere length. ObjectiveOur aim was to examine the association between serum ferritin concentrations, an indicator of body iron status, and leukocyte telomere length in US adults. DesignWe conducted a nationwide, population-based, cross-sectional study. Participants/settingWe used data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. We included 7,336 adults aged 20 years or older who had available data on serum ferritin levels and telomere length. High ferritin levels were defined as a serum ferritin level >200 ng/mL (449.4 pmol/L) in women and >300 ng/mL (674.1 pmol/L) in men. Low ferritin levels were defined as a serum ferritin level <30 ng/mL (67.4 pmol/L). Main outcome measuresLeukocyte telomere length was assayed using the quantitative polymerase chain reaction method. Statistical analysesLinear regression with survey weights was performed to estimate the association between serum ferritin levels and telomere length. ResultsThe prevalence of adults with high and low serum ferritin levels was 10.9% and 17.6%, respectively. High ferritin levels were inversely associated with telomere length compared to normal ferritin levels. After adjustment for demographic, socioeconomic and lifestyle factors, body mass index, C-reactive protein, and leukocyte cell type composition, the β coefficient for log-transformed telomere length was –0.020 (standard error [SE]=0.009; P=0.047). The association was stronger in adults aged 65 years or older (β coefficient –0.081, SE=0.017; P<0.001) than in adults 20 to 44 years old (β coefficient –0.023, SE=0.019; P=0.24) or adults aged 45 to 64 years old (β coefficient 0.024, SE=0.015; P=0.10) (P for interaction 0.003). Low ferritin levels were not significantly associated with telomere length compared with normal ferritin levels. ConclusionsIn a US nationally representative population, high body iron status was associated with shorter telomeres, especially in adults aged 65 years or older.

Network cultivation, diurnal cortisol and biological ageing: The rejuvenation hypothesis

A stronger motivation to cultivate social ties in older adults (ages range from 62 to 86 years) has been associated with a cortisol profile similar to that observed in undergraduate students, who are decades younger. We have shown the cultivation of social networks buffers against increases in diurnal cortisol common in old age. Cortisol is crucial for the response to stress and the process of ageing, and a recent study has demonstrated that a lower cortisol level is associated with longevity. We link the findings of social network cultivation and cortisol profile to the processes of biological ageing through DNA telomere length. Telomeres are repeated DNA sequences that cap and protect the ends of chromosomes, and telomere length is considered a potential biomarker for biological age because it is closely related to the cellular process of ageing and chronic stress and is inversely related to chronological age. Studies examining biological ageing have shown an association between an altered cortisol profile and telomere length dynamics. Together, these findings on social networks, cortisol profiles and telomere length suggest that seniors who are motivated to maintain social ties are biologically younger. We therefore propose the ‘rejuvenation hypothesis’, which posits that seniors with a stronger motivation for social network cultivation are biologically younger, as measured by cortisol levels and telomere length, than their peers who are less motivated to pursue social relationships. This idea suggests a new perspective and potentially fruitful direction for geriatric research. The focus on social network cultivation adds an important psychosocial dimension to rejuvenation therapies that so far have been dominated by biomedical approaches. The rejuvenation hypothesis also has important implications for social policy by supporting the viability of promoting network cultivation among the elderly to facilitate healthy ageing.

Retinal microcirculation and leukocyte telomere length in the general population

Retinal arteriolar narrowing increases with age and predict adverse cardiovascular outcomes. Telomere length keeps track of the division of somatic cells and is a biomarker of biological age. We investigated to what extent retinal arteriolar diameters are associated with biological age, as captured by leukocyte telomere length (LTL). In 168 randomly selected Flemish participants from the family-based population study FLEMENGHO (mean age, 46.2 years) at baseline, of whom 85 underwent a follow-up examination (median, 4.1 years), we post-processed nonmydriatic retinal photographs and measured LTL. In men only, central retinal arteriolar equivalents (CRAE) and arteriole-to-venule ratio (AVR) were associated with LTL with stronger associations at higher age and body mass index. In men aged 57.6 years (75th percentile) a 20% shorter LTL was associated with a decrease in CRAE of 4.57 µm. A 20% shorter LTL was associated with a decrease of 5.88 µm in CRAE at a BMI of 29.9 kg/m2 (75th percentile). Similar associations were observed between AVR and LTL. In women, no retinal microvascular traits were associated with LTL. Retinal arteriolar narrowing in men but not in women is associated with biological age. Our findings support the idea that avoiding overweight contributes to maintaining a healthier microcirculation.

Telomere biology and age-related diseases.

Telomeres are the protective end caps of chromosomes and shorten with every cell division. Telomere length has been proposed as a biomarker of biological age and a risk factor for age-related diseases. Epidemiologic studies show an association between leukocyte telomere length (LTL) and mortality. There is solid evidence that links LTL with cardiovascular disease. Short telomeres promote atherosclerosis and impair the repair of vascular lesions. Alzheimer's disease patients have also a reduced LTL. Telomeres measured in tumor tissue from breast, colon and prostate are shorter than in healthy tissue from the same organ and the same patient. In healthy tissue directly adjacent to these tumors, telomeres are also shorter than in cells that are more distant from the cancerous lesion. A reduced telomere length in cancer tissue from breast, colon and prostate is associated with an advanced disease state at diagnosis, faster disease progression and poorer survival. By contrast, results regarding LTL and cancer are inconsistent. Furthermore, the majority of studies did not find significant associations between LTL, bone mineral density (BMD) and osteoporosis. The present manuscript gives an overview about our current understanding of telomere biology and reviews existing knowledge regarding the relationship between telomere length and age-related diseases.

Short Telomere Length is Associated with Aging, Central Obesity, Poor Sleep and Hypertension in Lebanese Individuals.

In Lebanon, data stemming from national cross-sectional surveys indicated significant increasing trends in the prevalence of cardiovascular diseases and associated behavioral and age-related risk factors. To our knowledge, no data are available on relative telomere length (RTL) as a potential biomarker for age-related diseases in a Lebanese population. The aim of this study was to evaluate whether there is an association between RTL and demographic characteristics, lifestyle habits and diseases in the Lebanese. This was a cross-sectional study of 497 Lebanese subjects. Peripheral blood RTL was measured by amplifying telomere and single copy gene using real-time PCR. Mean ± SD RTL was 1.42 ± 0.83, and it was categorized into 3 tertiles. Older age (P=0.002) and wider waist circumference (WC) (P=0.001) were statistically significantly associated with shorter RTL. Multinomial logistic regression showed that subjects who had some level of sleeping difficulty had a statistically significantly shorter RTL when compared to those with no sleeping difficulties at all [OR (95% CI): 2.01 (1.11-3.62) in the first RTL tertile]. Importantly, statistically significantly shorter RTL was found with every additional 10 cm of WC [OR (95% CI): 1.30 (1.11-1.52) for first RTL tertile]. In addition, and after performing the multivariate logistic regression and adjusting for “predictors” of RTL, the odds of having hypertension or being treated for hypertension were higher in patients who had shorter RTL: OR (95% CI): 2.45 (1.36-4.44) and 2.28 (1.22-4.26) in the first RTL tertiles respectively with a similar trend, though not statistically significant, in the second RTL tertiles. This is the first study in Lebanon to show an association between age, central obesity, poor sleep and hypertension and RTL. It is hoped that telomere length measurement be potentially used as a biomarker for biological age and age-related diseases and progression in the Lebanese.

Circulating levels of monocyte chemoattractant protein-1 as a potential measure of biological age in mice and frailty in humans.

SummaryA serum biomarker of biological versus chronological age would have significant impact on clinical care. It could be used to identify individuals at risk of early‐onset frailty or the multimorbidities associated with old age. It may also serve as a surrogate endpoint in clinical trials targeting mechanisms of aging. Here, we identified MCP‐1/CCL2, a chemokine responsible for recruiting monocytes, as a potential biomarker of biological age. Circulating monocyte chemoattractant protein‐1 (MCP‐1) levels increased in an age‐dependent manner in wild‐type (WT) mice. That age‐dependent increase was accelerated in Ercc1 −/Δ and Bubr1 H/H mouse models of progeria. Genetic and pharmacologic interventions that slow aging of Ercc1 −/Δ and WT mice lowered serum MCP‐1 levels significantly. Finally, in elderly humans with aortic stenosis, MCP‐1 levels were significantly higher in frail individuals compared to nonfrail. These data support the conclusion that MCP‐1 can be used as a measure of mammalian biological age that is responsive to interventions that extend healthy aging.

Association Between Leukocyte Telomere Length and the Risk of Incident Atrial Fibrillation: The Framingham Heart Study.

BackgroundAdvancing age is a prominent risk factor for atrial fibrillation (AF). Shorter telomere length is a biomarker of biological aging, but the link between shorter telomere length and increased risk of AF remains unclear. We examined the association between shorter leukocyte telomere length (LTL) and incident AF.Methods and ResultsWe included AF‐free participants from the observational Framingham Heart Study Offspring cohort from 1995 to 1998, who had LTL measurements. We examined the association between baseline LTL and incident AF with multivariable Cox models adjusted for age, sex, current smoking, height, weight, systolic and diastolic blood pressure, use of antihypertensive medication, diabetes mellitus, history of myocardial infarction, and history of heart failure. The study sample comprised 1143 AF‐free participants (52.8% women), with mean age of 60±8 years. The mean LTL at baseline was 6.95±0.57 kb. During 15.1±4.2 years mean follow‐up, 184 participants (64 women) developed AF. Chronological age was associated with increased risk of AF (hazard ratio per 10‐year increase, 2.16; 95% confidence interval, 1.71–2.72). There was no significant association between LTL and incident AF (hazard ratio per 1 SD decrease LTL, 1.01; 95% confidence interval, 0.86–1.19). Our study was observational in nature; hence, we could not exclude residual confounding and we were unable to establish causal pathways.ConclusionsIn our moderate‐sized community‐based cohort, we did not find evidence for a significant association between LTL and risk of incident AF.

Epigenetic clock analysis in long-term meditators

In this paper, we examined whether meditation practice influences the epigenetic clock, a strong and reproducible biomarker of biological aging, which is accelerated by cumulative lifetime stress and with age-related chronic diseases. Using the Illumina 450K array platform, we analyzed the DNA methylome from blood cells of long-term meditators and meditation-naïve controls to estimate their Intrinsic Epigenetic Age Acceleration (IEAA), using Horvath's calculator. IEAA was similar in both groups. However, controls showed a different IEAA trajectory with aging than meditators: older controls (age≥52) had significantly higher IEAAs compared with younger controls (age <52), while meditators were protected from this epigenetic aging effect. Notably, in the meditation group, we found a significant negative correlation between IEAA and the number of years of regular meditation practice. From our results, we hypothesize that the cumulative effects of a regular meditation practice may, in the long-term, help to slow the epigenetic clock and could represent a useful preventive strategy for age-related chronic diseases. Longitudinal randomized controlled trials in larger cohorts are warranted to confirm and further characterize these findings.

Alpha- and Gamma-Tocopherol and Telomere Length in 5768 US Men and Women: A NHANES Study.

Antioxidants have a number of potential health benefits. The present investigation was designed to determine the relationship between serum alpha- and gamma-tocopherol levels (powerful antioxidants), and leukocyte telomere length (a biomarker of biological aging). A cross-sectional design was employed to study 5768 adults from the National Health and Nutrition Examination Survey (NHANES). DNA was obtained via blood samples. Telomere length was assessed using the quantitative polymerase chain reaction method. Serum concentrations of alpha- and gamma-tocopherol were measured using high performance liquid chromatography (HPLC). Results showed that for each one-year increase in age, telomeres were 15.6 base pairs shorter (F = 410.4, p < 0.0001). After adjusting for differences in the demographic covariates, for each µg/dL higher level of gamma-tocopherol, telomeres were 0.33 base pairs shorter (F = 7.1, p = 0.0126). Telomeres were approximately 1 year shorter (15.6 base pairs) for each increment of 47.3 to 55.7 µg/dL of gamma-tocopherol in the blood, depending on the variables controlled. Adults at the 75th percentile of gamma-tocopherol had 2.8–3.4 years greater cellular aging than those at the 25th percentile, depending on the covariates in the model. However, alpha-tocopherol was not related to telomere length. Evidently, gamma-tocopherol levels, but not alpha-tocopherol, account for meaningful increases in biological aging.

2D:4D finger length ratio and skeletal biomarker of biological aging.

The aim of this population-based study was to evaluate the association between the index to ring (2D:4D) finger length ratio and the osseographic score (OSS), the skeletal biomarker of biological aging. A sample included 802 males and 738 females who had participated in a Chuvashian skeletal aging study. Age, sex, basic demographics, anthropometric data and X-rays of both hands were collected. Each hand was visually classified on X-ray as either Type 1 - index finger was longer than ring finger; Type 2 - equal; or Type 3 - shorter than the ring finger. OSS is a skeletal biomarker that comprises osteoporotic and osteoarthritic changes observable on a hands X-ray. The mean age of males in the studies sample was 46.98 ± 17.10 and mean age females was 48.65 ± 16.62. OSS showed significant association with age (r = 0.886, p < 0.001), body mass index (BMI) (r-0.253, p < 0.001) and sex (F = 13.771, p < 0.001). Results of one-way ANCOVA for finger length ratio types of right hand showed a significant difference in OSS (d.f. = 2, F = 7.569, p = 0.001), after adjustment for age, sex, and BMI. The posthoc comparison showed that individuals with Type 3 (2D < 4D) ratio showed significantly higher OSS scores that ones with Type 1 (p = 0.012) and Type 2 (p = 0.003). In an analysis of finger length ratio types of left hand also a significant difference in OSS was found (d.f. = 2, F = 3.290, p = 0.038). The posthoc comparison showed that individuals with Type 3 (2D < 4D) ratio showed significantly higher OSS scores that ones with Type 2 (p = 0.33) ratio. Finger length ratio is associated with an OSS, a skeletal biomarker of biological aging. Individuals with Type 3 finger length pattern showed significantly higher OSS that ones with Type 1 and Type 2.

DNA methylation age-acceleration is associated with disease duration and age at onset in C9orf72 patients

The repeat expansion in C9orf72 is the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia. C9orf72 patients present with a wide range in disease duration and age of onset. The strongest risk factor for both syndromes is aging, which was linked to DNA methylation (DNAm) age based on the cumulative assessment of the methylation levels of 353 CpGs included on the genome-wide 450k BeadChip. DNAm age may reflect biological age better than chronological age. We conducted a genome-wide blood DNA methylation study of 46 unrelated C9orf72 patients. After correction for multiple testing, none of the CpGs demonstrated association between its methylation level and disease duration or age of onset. However, we detected a significant reverse correlation of DNAm age-acceleration with disease duration and age of onset, suggesting that for every 5-year increase in DNAm age-acceleration there is a 3.2-year earlier age of onset and 1.5-year shorter disease duration. The significant correlations remain after adjusting for gender, TMEM106B genotypes, disease phenotype and C9orf72 5′CpG island methylation status. A similar trend was observed for the blood DNA of affected members of an extended C9orf72 family; and tissues from the central nervous system of C9orf72 autopsy cases. For instance, regression analysis suggested that a 5-year increase in DNAm age-acceleration is linked to an earlier age of onset by 4.7 or 5.5 years for frontal cortex or spinal cord, respectively. Blood DNAm age may be a useful biomarker for biological age, because blood DNAm age-acceleration was similar to all investigated brain tissues, except for cerebellum that ages more slowly. In conclusion, DNA methylation analysis of C9orf72 patients revealed that increased DNAm age-acceleration is associated with a more severe disease phenotype with a shorter disease duration and earlier age of onset.

Blood DNA methylation age is not associated with cognitive functioning in middle-aged monozygotic twins

The epigenetic clock, also known as DNA methylation age (DNAmAge), represents age-related changes of DNA methylation at multiple sites of the genome and is suggested to be a biomarker for biological age. Elevated blood DNAmAge is associated with all-cause mortality, with the strongest effects reported in a recent intrapair twin study where epigenetically older twins had increased mortality risk in comparison to their co-twins. In the study presented here, we hypothesize that DNAmAge in blood is associated with cross-sectional and longitudinal cognitive abilities in middle-aged individuals. In 486 monozygotic twins, we investigated the association of DNAmAge, difference between DNAmAge and chronological age and age acceleration with cognition. Despite using a powerful paired twin design, we found no evidence for association of blood DNAmAge with cognitive abilities. This observation was confirmed in unpaired analyses, where DNAmAge initially correlated with cognitive abilities, until adjusting for chronological age. Overall, our study shows that for middle-aged individuals DNAmAge calculated in blood does not correlate with cognitive abilities.