scholarly journals Epigenetic clocks predict prevalence and incidence of leading causes of death and disease burden

Author(s):  
Robert F. Hillary ◽  
Anna J. Stevenson ◽  
Daniel L. McCartney ◽  
Archie Campbell ◽  
Rosie M. Walker ◽  
...  

AbstractIndividuals of the same chronological age display different rates of biological ageing. A number of measures of biological age have been proposed which harness age-related changes in DNA methylation profiles. These include methylation-based predictors of chronological age (HorvathAge, HannumAge), all-cause mortality (DNAm PhenoAge, DNAm GrimAge) and telomere length (DNAm Telomere Length). In this study, we test the association between these epigenetic markers of ageing and the prevalence and incidence of the leading causes of disease burden and mortality in high-income countries. Furthermore, we test the clocks’ relationships with phenotypic measures associated with these conditions, including spirometric and biochemical traits. We carry out these analyses in 9,537 individuals from the Generation Scotland: Scottish Family Health Study. We find that DNAm GrimAge outperforms other epigenetic clocks in its associations with self-report disease prevalence and related clinical traits. DNAm GrimAge associates with chronic obstructive pulmonary disease (COPD) prevalence (Odds Ratio = 3.29, P = 3.0 × 10-4) and pulmonary spirometry tests (β = [-0.10 to −0.15], P = [1.4 × 10-4 to 1.4 × 10-6]) at study baseline after adjusting for possibly confounding risk factors including alcohol, body mass index, deprivation, education and smoking. After adjusting for these confounding risk factors, DNAm GrimAge, DNAm PhenoAge and DNAm Telomere Length, measured at study baseline, predict incidence of ICD-10-coded disease states including COPD, type 2 diabetes and cardiovascular disease after thirteen years of follow-up (Hazard Ratios = [0.80 (telomere length) to 2.19 (GrimAge)], P = [9.9 × 10-4, 1.9 × 10-14]). Our data show that despite accounting for several possible confounding variables, epigenetic markers of ageing predict incidence of common disease. This may have significant implications for their potential utility in clinical settings to complement gold-standard methods of clinical assessment and management.

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S479-S479
Author(s):  
Waylon J Hastings ◽  
Daniel Belsky ◽  
Idan Shalev

Abstract Biological processes of aging are thought to be modifiable causes of many chronic diseases. Measures of biological aging could provide sensitive endpoints for studies of risk factors hypothesized to shorten healthy lifespan and/or interventions that extend it. However, uncertainty remains about how to measure biological aging and if proposed measures assess the same thing. We tested four proposed measures of biological aging with available data from NHANES 1999-2002: Klemera-Doubal method (KDM) Biological Age, homeostatic dysregulation, Levine Method (LM) Biological Age, and leukocyte telomere length. All measures of biological aging were correlated with chronological age. KDM Biological Age, homeostatic dysregulation, and LM Biological Age were all significantly associated with each other, but were each not associated with telomere length. NHANES participants with older biological ages performed worse on tests of physical, cognitive, perceptual, and subjective functions known to decline with advancing chronological age and thought to mediate age-related disability. Further, NHANES participants with higher levels of exposure to life-course risk factors were measured as having older biological ages. In both sets of analyses, effect-sizes tended to be larger for KDM Biological Age, homeostatic dysregulation, and LM Biological Age as compared to telomere length. Composite measures combining cellular- and patient-level information tended to have the largest effect-sizes. The cellular-level aging biomarker telomere length may measure different aspects of the aging process relative to the patient-level physiological measures. Studies aiming to test if risk factors accelerate aging or if interventions may slow aging should not treat proposed measures of biological aging as interchangeable.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Ezgi Yetim ◽  
Mehmet A Topcuoglu ◽  
Nuket Yurur Kutlay ◽  
Ajlan Tukun ◽  
Kader K Oguz ◽  
...  

Background: Telomeres are specific nucleotide repeats that play a central role in control of DNA damage related to cell division and aging. The degree of telomere shortening that occurs as part of aging is associated with age-related non-cancer diseases like hypertension, diabetes mellitus and coronary artery disease. Although a number of studies have highlighted that a similar relationship might exist with ischemic stroke, contradictory reports are also present in the literature. In this study we investigated the association between telomere length and ischemic stroke, not only in terms of stroke risk in general, but also from the perspective of stroke etiology and severity. Methods: In a Caucasian cohort, telomere length was determined by Southern blot from peripheral blood leukocytes in 163 consecutive ischemic stroke patients, and 210 controls without any prior history of ischemic stroke. Univariate and multivariate analyses were performed to determine the contribution of telomere length to stroke risk, stroke etiology, admission NIHSS score and DWI lesion volume. Results: The median (interquartile range) telomere length was 7.0 (5.5-9.0) kb in the overall population. Expectedly, telomere length was negatively correlated with aging (r=-0.23; p<0.001). A short telomere length (i.e. lowest quartile; ≤5.5 kb) was significantly associated with ischemic stroke (OR 3.0, 95%CI 1.8-5.1) when adjusted for age, gender and cardiovascular risk factors. This significant relationship persisted for all stroke etiologies, except for other rare causes of stroke. There was no significant relationship between admission lesion volume and telomere length; however, patients with short telomeres presented with more severe strokes (NIHSS score ≥16) when adjusted for age, risk factors, stroke etiology and infarct volume (OR 7.0; 95%CI 1.7-28.7). Conclusion: Almost all etiologic subtypes of ischemic stroke are related to shortened telomere length, irrespective of the age of the subject. Furthermore, presence of short telomeres negatively influences the tolerance of brain to ischemia, thereby causing more severe clinical phenotypes in these patients in the setting of ischemic stroke.


2018 ◽  
Vol 3 (1) ◽  
pp. 291-303 ◽  
Author(s):  
Monik C Jiménez ◽  
Katherine L Tucker ◽  
Fátima Rodriguez ◽  
Bianca C Porneala ◽  
James B Meigs ◽  
...  

Abstract Low blood dehydroepiandrosterone sulfate (DHEAS) levels have strong positive associations with stroke and coronary heart disease. However, it is unclear whether DHEAS is independently associated with cardiovascular risk factors. Therefore, we examined the association between cardiovascular risk factors and DHEAS concentration among a high-risk population of Latinos (Puerto Ricans aged 45 to 75 years at baseline) in a cross-sectional analysis of the Boston Puerto Rican Health Study. Of eligible participants, 72% completed baseline interviews and provided blood samples. Complete data were available for 1355 participants. Associations between cardiovascular risk factors (age, sex, total cholesterol, high-density lipid cholesterol, triglycerides, and glucose) and log-transformed DHEAS (μg/dL) were assessed. In robust multivariable regression analyses, DHEAS was significantly inversely associated with age (β = −12.4; 95% CI: −15.2, −9.7; per 5 years), being female (vs. male) (β = −46; 95% CI: −55.3, −36.6), and plasma triglyceride concentration (β = −0.2; 95% CI: −0.3, −0.1; per 10 mg/dL) and was positively associated with total cholesterol and plasma glucose levels (β = 1.8; 95% CI: 0.6, 3 and β = 0.2; 95% CI: 0.04, 0.3, respectively, per 10 mg/dL) after adjustment for smoking, alcohol, and physical activity and for postmenopausal hormone use in women. Estimates were unchanged after adjustment for measures of chronic disease and inflammation. Women exhibited a stronger age-related decline in DHEAS and a positive association with glucose in contrast to findings among men (Pinteraction &lt; 0.05). In conclusion, in this large study of Latinos with a heavy cardiovascular risk factor burden, we observed significant associations between cardiovascular disease (CVD) risk factors and DHEAS, with variations by sex. These findings improve our understanding of the role DHEAS may play in CVD etiology.


2018 ◽  
Vol 2 ◽  
Author(s):  
Eric O. Umeh ◽  
Kanayo F. Umeh ◽  
Uzoamaka R. Ebubedike ◽  
Chiamaka F. Ezeugbor ◽  
Chukwuziem N. Anene

Background: Breast cancer accounts for 25% of diagnosed cancers and 20% of cancer-related mortality in women from sub-Saharan Africa. Given the early onset of breast cancer in African women, there is a need to better understand how age-related risk factors contribute to mammography uptake in this population.Aim: To identify age-related risk factors for breast cancer associated with previous uptake of mammograms in asymptomatic Nigerian women and consider implications for health education campaigns.Method: Participants comprised 544 asymptomatic Nigerian women (aged 28–75 years) responding to breast cancer public awareness campaigns, by presenting for baseline or screening mammography at a local hospital. Information about mammography history and age-related risk factors (menarche, menopausal and chronological age) were obtained by interviewing the participants face-to-face, before proceeding with mammography. Hierarchical logistic regression was used to estimate the odds of previous mammograms based on the age-related risk factors.Results: The likelihood of previous mammography screening increased by a factor of 1.07 (95% confidence interval [CI]: 1.00–1.14) for every year older chronologically and decreased by a factor of 1.12 (95% CI: 1.24–1.01) for every year older at menarche. Age at menarche partly mediated the relationship between chronological age and mammography history (effect = –0.01, 95% CI: –0.01, –0.00). Women with a history of breast cancer were 6.11 times more likely to have previously undertaken mammography screening (95% CI: 2.49–14.97). Age at menopause and age at first confinement were unrelated to mammography history.Conclusions: Nigerian women may recognise the need for mammograms because of adverse age-related risk factors for breast cancer, notably menarche and chronological age. However, awareness of menopausal age as a risk factor and basis for mammography screening may be deficient. It is therefore recommended that public awareness campaigns should emphasise the importance of older menopausal age in breast cancer risk and as a basis for requesting mammograms.


Author(s):  
A. O. Radchenko ◽  
T. M. Bondar ◽  
A. V. Potapenko

Aging is characterized with a gradual aggravation of organ function throughout life and can occur both physiologically and prematurely. With premature aging there is an early decrease in the adaptive mechanisms of all physiological systems of the body, there is a significant reduction in physical and mental activities, that contributes to the early development of age−related pathology. Genetic and epigenetic factors, as well as environmental ones can be the causes of different rates of aging. It is not possible to accurately determine the onset of old age by biological characteristics, because people with the same calendar age are not always the same as for biological one. To establish the association of age−related disease factors with the markers of premature aging and biological age in the patients of various age groups, a study was performed in the patients aged 25−44 and 45−59 years with moderate cardiovascular risk in accordance with the SCORE scale. The primary task for predicting and preventing the age−associated diseases is to identify genetic, molecular and cellular factors that determine the rate of aging and increase the risk of age−associated diseases. The role of cardiovascular risk factors in premature aging has been determined. It is established that the most important factors that lead to an increase in biological age and formation of age−associated diseases are the disorders of lipid and carbohydrate metabolism and level of oxidative stress, importance of which progresses with age. The relationship between cardiovascular risk factors and biological age, estimated with different methods, their influence on telomere length, that allows the designing of an algorithm to determine the markers of premature aging in different age groups for early and effective prevention of metabolic−associated diseases, has been established. Key words: biological age, cardiovascular risk, premature aging, telomere length.


2021 ◽  
pp. bjophthalmol-2021-319621
Author(s):  
Jingxin He ◽  
Aiming Chen ◽  
Minjie Zou ◽  
Charlotte Aimee Young ◽  
Ling Jin ◽  
...  

PurposeTo evaluate the epidemiological trends and associated risk factors of disease burden due to trachoma.MethodsData for the country-specific disability-adjusted life year (DALY) number, rate and age-standardised rate of trachoma together with related data of other common eye diseases were acquired from the Global Burden of Disease Study 2019 database. The Socio-Demographic Index (SDI), Human Development Index (HDI), inequality-adjusted HDI and other related indices were obtained from published data or publicly available databases. Regression analyses were conducted to evaluate the associations between potential risk factors and the age-standardised DALY burden of trachoma.ResultsThe global DALY burden due to trachoma decreased by 37% from 1990 to 2019 and decreased by 69.8% after adjusting for age and population growth, and, in available 1990–2019 data, had the greatest reduction in attributable DALYs of all common eye disease, with the others analysed being cataract, glaucoma, refractive disorders and age-related macular degeneration. Women had higher age-standardised DALY burden due to trachoma than men (p<0.001). The African region (p<0.001) had the heaviest burden among global regions. The age-standardised DALY rate was higher in countries with lower income (p<0.001) and lower SDI (p<0.001). Higher disease burden due to trachoma was associated with lower HDI (β=−48.102, 95% CI −86.888 to −9.316, p=0.016), lower SDI (β=−48.063, 95% CI −83.702 to −12.423, p<0.001) and lower expected years of schooling (β=−2.352, 95% CI −3.756 to −0.948, p=0.002).ConclusionsThe global disease burden due to trachoma decreased from 1990 to 2019 and it had the greatest reduction compared with other common eye diseases. Lower HDI, socioeconomic status and educational level were related to a higher national disease burden of trachoma. Our findings could provide necessary information for trachoma control and prevention.


2021 ◽  
Vol 9 ◽  
Author(s):  
Efraim Jaul ◽  
Jeremy Barron

Introduction: Older adulthood encompasses several decades of change and heterogeneity. Primary care providers need a geriatric comprehensive vision for defining older adult subpopulations.Methods: Using PubMed and Google searches, we reviewed the literature on epidemiology of age-related physiological changes, age-related diseases and geriatric syndromes, functional state, and emotional and social changes. We divided old age into strata based on chronological age and strata based on functional state, disease burden, and geriatric syndromes.Results: We describe 4 chronological-age strata beginning at age 60, and 4 functional-age strata based on frailty according to a modified clinical frailty scale. We provide clinical considerations and anticipatory guidance topics for each of the age strata and functional strata.Conclusion: Chronological age, functional status, chronic disease burden and geriatric syndromes, and life expectancy are all important domains that impact clinical care and appropriate anticipatory guidance for individual older adults. Better knowledge for differentiating subpopulations of older adults may improve clinical care, reduce medical overuse, improve personalized anticipatory guidance, and focus on the impact of functional state on the quality of life.


2020 ◽  
pp. 174239532095943
Author(s):  
Tara C Klinedinst ◽  
Tracy L Nelson ◽  
Gene W Gloeckner ◽  
Matt P Malcolm

Objectives Individuals with type 2 diabetes are at risk for deficits in instrumental activities of daily living (IADL: e.g., managing medication, preparing healthy meals). Understanding which demographic and health factors contribute to decreased frequency of IADL performance is especially important to prevent age-related functional decline in type 2 diabetes. This study examined the relationships among demographic and health variables and frequency of IADL performance in adults with type 2 diabetes. Methods For this cross-sectional study, we collected health, demographic, and activity information via self-report and electronic health record review from safety-net primary care patients with type 2 diabetes (n = 93). We used regression models to determine which factors were associated with IADL performance in three subscales (domestic, leisure/work, outdoor) and the overall score. Results Depression was associated with decreased frequency of IADL performance for domestic, leisure/work, and outdoor activities. Each additional daily medication was associated with decreased frequency of domestic and outdoor IADL performance. Discussion Depression and taking more daily medication were predictors of decreased IADL performance for adults with type 2 diabetes. Our findings suggest regular screening for depression and polypharmacy is important in the primary care of diabetes; especially as these are potentially modifiable risk factors.


2011 ◽  
Vol 67A (4) ◽  
pp. 409-416 ◽  
Author(s):  
J. L. Sanders ◽  
A. L. Fitzpatrick ◽  
R. M. Boudreau ◽  
A. M. Arnold ◽  
A. Aviv ◽  
...  

2021 ◽  
pp. bjophthalmol-2021-318828
Author(s):  
Julia V. Stingl ◽  
Sol A Ban ◽  
Markus Nagler ◽  
Irene Schmidtmann ◽  
Philipp S. Wild ◽  
...  

Background/AimsTo examine the 5-year change in refractive error in phakic eyes and its risk factors in the general population.MethodsThe Gutenberg Health Study (GHS) is a population-based cohort study including 15 010 participants from Germany aged 35–74 years at baseline examination (2007–2012). After 5 years, a follow-up examination was carried out (83% participation). 5-year change of spherical equivalent (SE) was computed as difference between follow-up and baseline objective refraction. Linear and logistic regression analysis were conducted analysing potential risk factors. Only phakic eyes at follow-up examination were included.ResultsRight eyes of 10 175 subjects were included. An age-related shift of refractive error was identified, namely −0.12 D for age 35–44 years, 0.25 D for age 45–54 years, 0.25 D for age 55–64 years and 0.12 D for age 65–74 years during the 5-year follow-up. Smokers had a hyperopic shift (OR=1.31; p<0.001), while baseline SE (OR=0.89 per dioptre; p<0.001) and female sex (OR=1.49; p<0.001) were linked with a myopic shift. Education, occupation and other cardiovascular parameters were not associated with change in refractive error.ConclusionsThe GHS demonstrates a parabolic shift in refractive error with a myopic shift at age 35–44 years, followed by a hyperopic shift at age 45–64 years which decreases at higher age. Smoking is associated with a hyperopic shift whereas female sex and myopic baseline SE is associated with a myopic shift. Educational level and occupation were not linked to a change in refractive error at age 35–74 years.


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