scholarly journals Childhood intelligence attenuates the association between biological ageing and health outcomes in later life

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna J. Stevenson ◽  
Daniel L. McCartney ◽  
Robert F. Hillary ◽  
Paul Redmond ◽  
Adele M. Taylor ◽  
...  

AbstractThe identification of biomarkers that discriminate individual ageing trajectories is a principal target of ageing research. Some of the most promising predictors of biological ageing have been developed using DNA methylation. One recent candidate, which tracks age-related phenotypes in addition to chronological age, is ‘DNAm PhenoAge’. Here, we performed a phenome-wide association analysis of this biomarker in a cohort of older adults to assess its relationship with a comprehensive set of both historical, and contemporaneously-measured, phenotypes. Higher than expected DNAm PhenoAge compared with chronological age, known as epigenetic age acceleration, was found to associate with a number of blood, cognitive, physical fitness and lifestyle variables, and with mortality. Notably, DNAm PhenoAge, assessed at age 70, was associated with cognitive ability at age 11, and with educational attainment. Adjusting for age 11 cognitive ability attenuated the majority of the cross-sectional later-life associations between DNAm PhenoAge and health outcomes. These results highlight the importance of early life factors on healthy older ageing.

2019 ◽  
Author(s):  
Anna J. Stevenson ◽  
Daniel L. McCartney ◽  
Robert F. Hillary ◽  
Paul Redmond ◽  
Adele M. Taylor ◽  
...  

AbstractThe identification of biomarkers that discriminate individual ageing trajectories is a principal target in ageing research. Some of the most promising predictors of biological ageing have been developed using DNA methylation. One recent candidate, which tracks age-related phenotypes in addition to chronological age, is ‘DNAm PhenoAge’. Here, we performed a phenome-wide association analysis of this biomarker in a cohort of older adults to assess its relationship with a comprehensive set of both historical and contemporaneously-measured phenotypes. Higher than expected DNAm PhenoAge compared to chronological age, known as epigenetic age acceleration, was found to associate with a number of blood, cognitive, physical fitness and lifestyle variables, and with mortality. Notably, DNAm PhenoAge, assessed at age 70, was associated with cognitive ability at age 11, and with educational attainment. Adjusting for age 11 cognitive ability attenuated the majority of the cross-sectional later-life associations between DNAm PhenoAge and health outcomes. These results highlight the importance of early-life factors on healthy ageing.


Author(s):  
Cathal McCrory ◽  
Giovanni Fiorito ◽  
Sinead McLoughlin ◽  
Silvia Polidoro ◽  
Cliona Ni Cheallaigh ◽  
...  

Abstract Allostatic load (AL) and epigenetic clocks both attempt to characterize the accelerated aging of biological systems, but at present it is unclear whether these measures are complementary or distinct. This study examines the cross-sectional association of AL with epigenetic age acceleration (EAA) in a subsample of 490 community-dwelling older adults participating in The Irish Longitudinal study on Aging (TILDA). A battery of 14 biomarkers representing the activity of four different physiological systems: immunological, cardiovascular, metabolic, renal, was used to construct the AL score. DNA methylation age was computed according to the algorithms described by Horvath, Hannum, and Levine allowing for estimation of whether an individual is experiencing accelerated or decelerated aging. Horvath, Hannum, and Levine EAA correlated 0.05, 0.03, and 0.21 with AL, respectively. Disaggregation by sex revealed that AL was more strongly associated with EAA in men compared with women as assessed using Horvath’s clock. Metabolic dysregulation was a strong driver of EAA in men as assessed using Horvath and Levine’s clock, while metabolic and cardiovascular dysregulation were associated with EAA in women using Levine’s clock. Results indicate that AL and the epigenetic clocks are measuring different age-related variance and implicate sex-specific drivers of biological aging.


GeroPsych ◽  
2016 ◽  
Vol 29 (4) ◽  
pp. 177-187 ◽  
Author(s):  
Allyson S. Graf ◽  
Julie Hicks Patrick

Abstract. Self-assessed health (SAH) is the personal assessment of one’s own health ( Idler & Benyamini, 1997 ; Jylhä, 2009 ). It is often measured using a single item asking whether adults rate their health as excellent, very good, good, fair, or poor. When measured at a single point in time, SAH relates to a variety of short-term and long-term health outcomes and behaviors, including morbidity, healthcare utilization, and mortality ( Benyamini, 2008 ; Mossey & Shapiro, 1982 ; Westerhof & Wurm, 2015 ). Recently, attention has shifted away from examining SAH at a single point in time toward understanding whether SAH trajectories can better predict health outcomes ( Ayyagari et al., 2012 ; Schmitz et al., 2013 ). Therefore, it is critical to understand the factors contributing to the SAH process. This article provides a multidisciplinary overview of SAH and SAH change while illustrating the benefits of adopting a lifespan approach in future research. The current SAH literature, including cross-sectional and longitudinal studies, is used to examine what is known about the SAH process into late adulthood. From the literature, it is clear SAH is a multidimensional construct, susceptible to age-related change and sociohistorical contexts. Understanding the developmental mechanisms and multiple influences underlying change, however, may help further the use of SAH as a life-long health-promotion tool. Lifespan concepts are applied to expand discussion and recommendations are made concerning the application of alternative variables and methodologies. Future studies of SAH should consider these personal perceptions of health not only as predictors of health outcomes in later life, but also as tools for effective health promotion in everyday life.


Author(s):  
Brian Joyce ◽  
Tao Gao ◽  
Yinan Zheng ◽  
Jiantao Ma ◽  
Shih-Jen Hwang ◽  
...  

Rationale: Epigenetic aging is a novel measure of biological age, reflecting exposures and disease risks independent of chronological age. It may serve as a useful biomarker of cardiovascular health (CVH) and/or cardiovascular disease (CVD) risk for early detection or prevention. Objective: To examine associations between GrimAge acceleration (GrimAA), a measure of epigenetic aging calculated from the residuals of GrimAge regressed on chronological age, and two repeated CVH measures: a full score for the AHA "Life's Simple 7" (diet, smoking, physical activity, BMI, blood pressure, total cholesterol, and glucose) and a clinical CVH score (BMI, blood pressure, cholesterol, and glucose). Methods and Results: We used Illumina array DNA methylation data from two prospective cohort studies: The Coronary Artery Risk Development in Young Adults (CARDIA) study and Framingham Heart Study (FHS), to calculate GrimAA and model associations with CVH. CARDIA randomly selected 1,118 participants for assays at Y15 (2000-2001; mean age 40) and/or Y20 (2005-2006); in FHS, 2,106 Offspring participants had DNA methylation measured at exam 8 (2005-2008; mean age 66). We examined multiple cross-sectional and longitudinal models of GrimAA and each CVH score measured at CARDIA Y0-Y20 and FHS exams 7-8. In CARDIA clinical CVH score from Y0-Y20 was associated with Y15 and Y20 GrimAA (β range -0.41 to -0.21 years per 1-point increase in CVH; p range <0.01 to 0.01), as was full score (β range -0.65 to -0.67 years; p<0.01 for all). These findings were validated in FHS (clinical score β range -0.51 to -0.54 years; full score β range -0.76 to -0.83 years; p<0.01 for all). Conclusions: Our data demonstrate that faster GrimAA is associated with the loss of CVH from young age. Epigenetic age may be a useful biomarker of CVD risk and provides biological insight into the role of epigenetic mechanisms linking age-related CVH loss and CVD.


Author(s):  
Lili Xiao ◽  
Gaohui Zan ◽  
Chaoqun Liu ◽  
Xia Xu ◽  
Longman Li ◽  
...  

Background Individuals of the same chronological age may exhibit diverse susceptibilities to death. However, few studies have investigated the associations between blood pressure and the accelerated aging. Methods and Results A cross‐sectional study was conducted in 288 adults aged ≥50 years. We assessed the DNA methylation‐based measures of biological age using CpG sites on the Illumina HumanMethylationEPIC BeadChip. Epigenetic age acceleration metrics were derived by regressing residuals (ΔAge) and ratios (aging rate) of DNA methylation age on chronological age. Dose‐response relationships between blood pressure and epigenetic age acceleration were quantified using multiple linear regression and restricted cubic regression models. We found that each 10–mm Hg increase in systolic blood pressure was associated with 0.608 (95% CI, 0.231–0.984) years increase in ΔAge and 0.007 (95% CI, 0.002–0.012) increase in aging rate; meanwhile, for pulse pressure, the increase was 1.12 (95% CI, 0.625–1.61) years for ΔAge and 0.013 (95% CI, 0.007–0.020) for aging rate. Subgroup analysis showed that the significant associations of systolic blood pressure and pulse pressure with epigenetic age acceleration appeared to be limited to women, although interactions between blood pressure and sex were not significant ( P values for interaction >0.05). The combination of women and hypertension was associated with a much higher increase in ΔAge (β [95% CI], 4.05 [1.07–7.02]) and aging rate (β [95% CI], 0.047 [0.008–0.087]), compared with male participants without hypertension. Conclusions Our findings suggested that high systolic blood pressure and pulse pressure were associated with the epigenetic age acceleration, providing important clues for relationships between blood pressure and epigenetic aging.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M W Christensen ◽  
D Keefe ◽  
F Wang ◽  
C Hansen ◽  
I Chamani ◽  
...  

Abstract Study question Do young women with idiopathic early ovarian ageing have changes in telomere length and epigenetic age indicating accelerated biological aging? Summary answer The telomere length and epigenetic age were comparable to those in young women with normal ovarian ageing. What is known already Increased risk of several health events usually considered to be age-related such as cardiovascular disease, osteoporosis, over-all morbidity and mortality have been associated with premature and early menopause when compared to the risk in women with normal menopausal age suggesting an accelerated general ageing process associated to early ovarian ageing. It is unclear whether the onset of this process may start before menopause. Study design, size, duration A prospective cohort study. Young women (≤ 37 years) having ART at two Danish Public fertility clinics during the period 2016 to 2018 were divided into two groups dependent on their ovarian reserve status: early ovarian ageing (EOA) (N = 55) and normal ovarian ageing (NOA)( N = 52). Number of oocytes harvested in first and subsequent cycles was used as a marker of ovarian reserve. Blood samples was drawn at time of oocyte retrieval to assess biological age. Participants/materials, setting, methods EOA was defined as ≥ 2 IVF cycles with ≤ 5 harvested oocytes despite sufficient stimulation with FSH and NOA as ≥ 8 oocytes harvested in minimum 1 cycle. Known causes influencing the ovarian reserve (endometriosis, ovarian surgery, etc.) was reason for exclusion. Relative telomere length (qPCR) and epigenetic age acceleration (DNA methylation levels) were measured in white blood cells as markers of accelerated biological ageing. Main results and the role of chance Relative telomere length was comparable with a mean of 0.46 (± sd 0.12) in the EOA group and 0.47 (0.14) in the normal ovarian ageing group (p = 0.64). The difference of predicted mean epigenetic age and mean chronological age (i.e. epigenetic age acceleration) was, insignificantly, 0.5 years older in the EOA group when compared to the NOA group( (–1.02 years (2.62) and –1.57 years (2.56), respectively, p = 0.27)), but this difference disappeared when adjusting for chronological age. Limitations, reasons for caution Discrete changes in epigenetic age acceleration may not have been captured as the study only had power to detect an age acceleration of ≥ 2 years. Wider implications of the findings: By analysis of biomarkers for ageing in whole blood, we did not find any indications of a premenopausal accelerated aging in young women with idiopathic EOA. Further investigations in a similar cohort of premenopausal women is needed to fully elucidate the potential relationship between premenopausal accelerated biological ageing and EOA. Trial registration number The study was approved by the Danish Data protection Agency (nr 1–16–02–320–14) and the Regional committee on health research ethics of Central Region Denmark (jr.no 1–10–72–142–14).


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Tess D. Pottinger ◽  
Sadiya S. Khan ◽  
Yinan Zheng ◽  
Wei Zhang ◽  
Hilary A. Tindle ◽  
...  

Abstract Background Cardiovascular health (CVH) has been defined by the American Heart Association (AHA) as the presence of the “Life’s Simple 7” ideal lifestyle and clinical factors. CVH is known to predict longevity and freedom from cardiovascular disease, the leading cause of death for women in the United States. DNA methylation markers of aging have been aggregated into a composite epigenetic age score, which is associated with cardiovascular morbidity and mortality. However, it is unknown whether poor CVH is associated with acceleration of aging as measured by DNA methylation markers in epigenetic age. Methods and results We performed a cross-sectional analysis of racially/ethnically diverse post-menopausal women enrolled in the Women’s Health Initiative cohort recruited between 1993 and 1998. Epigenetic age acceleration (EAA) was calculated using DNA methylation data on a subset of participants and the published Horvath and Hannum methods for intrinsic and extrinsic EAA. CVH was calculated using the AHA measures of CVH contributing to a 7-point score. We examined the association between CVH score and EAA using linear regression modeling adjusting for self-reported race/ethnicity and education. Among the 2,170 participants analyzed, 50% were white and mean age was 64 (7 SD) years. Higher or more favorable CVH scores were associated with lower extrinsic EAA (~ 6 months younger age per 1 point higher CVH score, p < 0.0001), and lower intrinsic EAA (3 months younger age per 1 point higher CVH score, p < 0.028). Conclusions These cross-sectional observations suggest a possible mechanism by which ideal CVH is associated with greater longevity.


Author(s):  
Mei Sum Chan ◽  
Matthew Arnold ◽  
Alison Offer ◽  
Imen Hammami ◽  
Marion Mafham ◽  
...  

Abstract Background Chronological age is the strongest risk factor for most chronic diseases. Developing a biomarker-based age and understanding its most important contributing biomarkers may shed light on the effects of age on later-life health and inform opportunities for disease prevention. Methods A subpopulation of 141 254 individuals healthy at baseline were studied, from among 480 019 UK Biobank participants aged 40–70 recruited in 2006–2010, and followed up for 6–12 years via linked death and secondary care records. Principal components of 72 biomarkers measured at baseline were characterized and used to construct sex-specific composite biomarker ages using the Klemera Doubal method, which derived a weighted sum of biomarker principal components based on their linear associations with chronological age. Biomarker importance in the biomarker ages was assessed by the proportion of the variation in the biomarker ages that each explained. The proportions of the overall biomarker and chronological age effects on mortality and age-related hospital admissions explained by the biomarker ages were compared using likelihoods in Cox proportional hazard models. Results Reduced lung function, kidney function, reaction time, insulin-like growth factor 1, hand grip strength, and higher blood pressure were key contributors to the derived biomarker age in both men and women. The biomarker ages accounted for &gt;65% and &gt;84% of the apparent effect of age on mortality and hospital admissions for the healthy and whole populations, respectively, and significantly improved prediction of mortality (p &lt; .001) and hospital admissions (p &lt; 1 × 10−10) over chronological age alone. Conclusions This study suggests that a broader, multisystem approach to research and prevention of diseases of aging warrants consideration.


2021 ◽  
Vol 13 ◽  
Author(s):  
Pei-Lun Kuo ◽  
Ann Zenobia Moore ◽  
Frank R. Lin ◽  
Luigi Ferrucci

Objectives: Age-related hearing loss (ARHL) is highly prevalent among older adults, but the potential mechanisms and predictive markers for ARHL are lacking. Epigenetic age acceleration has been shown to be predictive of many age-associated diseases and mortality. However, the association between epigenetic age acceleration and hearing remains unknown. Our study aims to investigate the relationship between epigenetic age acceleration and audiometric hearing in the Baltimore Longitudinal Study of Aging (BLSA).Methods: Participants with both DNA methylation and audiometric hearing measurements were included. The main independent variables are epigenetic age acceleration measures, including intrinsic epigenetic age acceleration—“IEAA,” Hannum age acceleration—“AgeAccelerationResidualHannum,” PhenoAge acceleration—“AgeAccelPheno,” GrimAge acceleration—“AgeAccelGrim,” and methylation-based pace of aging estimation—“DunedinPoAm.” The main dependent variable is speech-frequency pure tone average. Linear regression was used to assess the association between epigenetic age acceleration and hearing.Results: Among the 236 participants (52.5% female), after adjusting for age, sex, race, time difference between measurements, cardiovascular factors, and smoking history, the effect sizes were 0.11 995% CI: (–0.00, 0.23), p = 0.054] for Hannum’s clock, 0.08 [95% CI: (–0.03, 0.19), p = 0.143] for Horvath’s clock, 0.10 [95% CI: (–0.01, 0.21), p = 0.089] for PhenoAge, 0.20 [95% CI: (0.06, 0.33), p = 0.004] for GrimAge, and 0.21 [95% CI: (0.09, 0.33), p = 0.001] for DunedinPoAm.Discussion: The present study suggests that some epigenetic age acceleration measurements are associated with hearing. Future research is needed to study the potential subclinical cardiovascular causes of hearing and to investigate the longitudinal relationship between DNA methylation and hearing.


Author(s):  
Pavanello ◽  
Campisi ◽  
Tona ◽  
Lin ◽  
Iliceto

DNA methylation (DNAm) is an emerging estimator of biological aging, i.e., the often-defined “epigenetic clock”, with a unique accuracy for chronological age estimation (DNAmAge). In this pilot longitudinal study, we examine the hypothesis that intensive relaxing training of 60 days in patients after myocardial infarction and in healthy subjects may influence leucocyte DNAmAge by turning back the epigenetic clock. Moreover, we compare DNAmAge with another mechanism of biological age, leucocyte telomere length (LTL) and telomerase. DNAmAge is reduced after training in healthy subjects (p = 0.053), but not in patients. LTL is preserved after intervention in healthy subjects, while it continues to decrease in patients (p = 0.051). The conventional negative correlation between LTL and chronological age becomes positive after training in both patients (p < 0.01) and healthy subjects (p < 0.05). In our subjects, DNAmAge is not associated with LTL. Our findings would suggest that intensive relaxing practices influence different aging molecular mechanisms, i.e., DNAmAge and LTL, with a rejuvenating effect. Our study reveals that DNAmAge may represent an accurate tool to measure the effectiveness of lifestyle-based interventions in the prevention of age-related diseases.


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