Validation of biomarkers of aging

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(2), P. 360 - 372

Published: Feb. 1, 2024

Language: Английский

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Deciphering the role of immune cell composition in epigenetic age acceleration: Insights from cell‐type deconvolution applied to human blood epigenetic clocks

Aging Cell, Journal Year: 2023, Volume and Issue: 23(3)

Published: Dec. 25, 2023

Abstract Aging is a significant risk factor for various human disorders, and DNA methylation clocks have emerged as powerful tools estimating biological age predicting health‐related outcomes. Methylation data from blood has been focus of more recently developed clocks. However, the impact immune cell composition on epigenetic acceleration (EAA) remains unclear only some incorporate partial type information when analyzing EAA. We investigated associations 12 types measured by cell‐type deconvolution with EAA predicted six widely‐used in >10,000 samples. observed all tested. Across clocks, nine or tested exhibited Higher memory lymphocyte subtype proportions were associated increased EAA, naïve subtypes decreased To demonstrate potential confounding composition, we applied rheumatoid arthritis. Our research maps contributions to offers opportunities adjust studies significantly granular level. Understanding profiles implications interpretation its relevance aging disease research. detailed map serves resource utilizing across diverse fields, including aging‐related diseases, precision medicine, therapeutic interventions.

Language: Английский

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Epigenetic Aging and Racialized, Economic, and Environmental Injustice

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(7), P. e2421832 - e2421832

Published: July 29, 2024

Importance Epigenetic age acceleration is associated with exposure to social and economic adversity may increase the risk of premature morbidity mortality. However, no studies have included measures structural racism, few compared estimates within or across first second generation epigenetic clocks. Objective To determine whether positively exposures diverse racialized, economic, environmental injustice measured at different levels time periods. Design, Setting, Participants This cross-sectional study used data from My Body Story (MBMS) between August 8, 2008, December 31, 2010, examination 5 Multi-Ethnic Atherosclerosis Study (MESA) April 1, February 29, 2012. In MBMS, DNA extraction was performed in 2021; linkage MBMS MESA, 2022. US-born individuals were randomly selected 4 community health centers Boston, Massachusetts (MBMS), field sites Baltimore, Maryland; Forsyth County, North Carolina; New York City, York; St Paul, Minnesota (MESA). Data analyzed November 13, 2021, 2023. Main Outcomes Measures Ten clocks (6 first-generation second-generation), computed using methylation (DNAm) blood spots purified monocytes Results The population 293 participants (109 men [37.2%], 184 women [62.8%]; mean [SD] age, 49.0 [8.0] years) 224 Black non-Hispanic 69 White 975 MESA (492 [50.5%], 483 [49.5%]; 70.0 [9.3] 229 non-Hispanic, 191 Hispanic, 555 participants. Of these, 140 (11.0%) exhibited accelerated aging for all whose are interpretable on (years) scale. Among participants, being born a Jim Crow state by 0.14 (95% CI, 0.003-0.27) SDs birth conservatism 0.06 0.01-0.12) SDs, pooling Low parental educational level acceleration, clocks, both (0.24 [95% 0.08-0.39] SDs) (0.27 0.03-0.51] Adult impoverishment pooled second-generation among (Black 0.01-0.12] SDs; 0.07 0.01-0.14] 0.05 0.01-0.08] SDs). Conclusions Relevance findings this suggest that racialized injustice, potentially contributing well-documented inequities Future research should test hypothesis be one biological mechanisms underlying elevated mortality groups subjected injustice.

Language: Английский

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Body Size, Diet Quality, and Epigenetic Aging: Cross-Sectional and Longitudinal Analyses

The Journals of Gerontology Series A, Journal Year: 2024, Volume and Issue: 79(4)

Published: Jan. 24, 2024

Epigenetic age is an emerging marker of health that highly predictive disease and mortality risk. There a lack evidence on whether lifestyle changes are associated with in epigenetic aging. We used data from 1 041 participants the Melbourne Collaborative Cohort Study blood DNA methylation measures at baseline (1990-1994, mean age: 57.4 years) follow-up (2003-2007, 68.8 years). The Alternative Healthy Eating Index-2010 (AHEI-2010), Mediterranean Dietary Score, Inflammatory Index were as diet quality, weight, waist circumference, waist-to-hip ratio body size. Five age-adjusted aging considered: GrimAge, PhenoAge, PCGrimAge, PCPhenoAge, DunedinPACE. Multivariable linear regression models including restricted cubic splines to assess cross-sectional longitudinal associations size quality Associations between weight cross-sectionally both time points positive appeared greater for DunedinPACE (per SD: β ~0.24) than GrimAge PhenoAge (β ~0.10). change markedly nonlinear (U-shaped) stable being lowest follow-up, except DunedinPACE, which only gain showed association. found negative, AHEI-2010 longitudinally. Other adiposity dietary scores similar results. In middle-aged older adults, declining may increase age, while association loss require further investigation. Our study sheds light potential management improvement slowing processes.

Language: Английский

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Sexual minority stress and epigenetic aging

Brain Behavior and Immunity, Journal Year: 2025, Volume and Issue: 126, P. 24 - 29

Published: Jan. 31, 2025

Language: Английский

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Epigenetic age acceleration is related to cognitive decline in the elderly: Results of the Austrian Stroke Prevention Study

Psychiatry and Clinical Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Epigenetic clocks, quantifying biological age through DNA methylation (DNAmAge), have emerged as potential indicators of brain aging. As the variety DNAmAge algorithms grows, consensus on their efficacy in predicting age-related changes is lacking. This study aimed to explore intricate relationship between diverse and structural cognitive markers Within a cohort 796 elderly patients (mean age, 65.8 ± 7.9 years), we scrutinized 11 algorithms, including Horvath, Hannum, Zhang's PhenoAge, GrimAge, DunedinPACE, principal component (PC)-based PCHorvath, PCHannum, PCPhenoAge, PCGrimAge. We evaluated association with baseline cognition decline, assessed follow-up evaluations at three (T1) six (T2) years postbaseline. Additionally, examined magnetic resonance imaging aging, white matter. clock was best predictor decline memory (β = -0.04) global -0.03), whereas PCGrimAge speed -0.17). The were second-best predictors explaining variability after education (R2 partial 1.66% 2.82%) for 2.13%). PC-trained outperformed respective original version. are strong independent normal population explain additional beyond that accounted by conventional risk factors.

Language: Английский

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Lead and cadmium exposure was associated with faster epigenetic aging in a representative sample of adults aged 50 and older in the United States

Chemosphere, Journal Year: 2025, Volume and Issue: 374, P. 144194 - 144194

Published: Feb. 12, 2025

Language: Английский

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Uncertainty Quantification in Epigenetic Clocks via Conformalized Quantile Regression

Genetic Epidemiology, Journal Year: 2025, Volume and Issue: 49(4)

Published: March 27, 2025

ABSTRACT DNA methylation (DNAm) is a chemical modification of that can be influenced by various factors, including age, the environment, and lifestyle. An epigenetic clock predictive tool measures biological age based on DNAm levels. It provide insights into an individual's which may differ from their chronological age. This difference, known as acceleration, reflect health status risk for age‐related diseases. Moreover, clocks are used in studies aging to assess effectiveness antiaging interventions understand underlying mechanisms disease. Various have been developed using samples different populations, tissues, cell types, typically training high‐dimensional linear regression models with elastic net penalty. While these predict mean high precision, there lack uncertainty quantification important interpreting precision estimations clinical decision‐making. To distribution beyond its mean, we propose general pipeline clocks, integration quantile conformal prediction, effectively reveal population heterogeneity construct prediction intervals. Our approach produces adaptive intervals not only achieving nominal coverage but also accounting inherent variability across individuals. By data collected 728 blood 11 sets children, find our regression‐based narrower than those derived conventional clocks. observation demonstrates improved statistical efficiency over existing In addition, resulting synchronized varying pattern revealing cellular evolutionary patterns developmental stages during individual childhoods adolescent cohort. findings suggest conformalized produce valid uncover heterogeneity. Although methodology focuses it applicable broader range groups improve understanding mean. inference‐based toolbox could valuable future applications

Language: Английский

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Early-life risk factors, accelerated biological aging and the late-life risk of mortality and morbidity

QJM, Journal Year: 2023, Volume and Issue: 117(4), P. 257 - 268

Published: Nov. 1, 2023

Summary Background Early-life exposure increases health risks throughout an individual’s lifetime. Biological aging is influenced by early-life as a key process of disease development, but whether could accelerate biological and elevate late-life mortality morbidity remains unknown. Knowledge also limited on the potential moderating role healthy lifestyle. Methods We investigate associations three around birth, breastfeeding, maternal smoking birth weight, with 202 580 UK Biobank participants (54.9 ± 8.1 years old). was quantified KDM-BA, PhenoAge frailty. Moderate alcohol intake, no current smoking, diet, BMI <30 kg/m2 regular physical activity were considered lifestyles. Mortality data retrieved from records. Results Individual risk factors robustly associated accelerated aging. A one-unit increase in ‘early-life score’ integrating 0.060 (SE=0.0019) 0.036-unit (SE = 0.0027) z-scored KDM-BA acceleration acceleration, respectively, 22.3% higher odds (95% CI: 1.185–1.262) Increased chronological age lifestyles mitigate accelerations PhenoAge, respectively. Associations score mediated (proportions: 5.66–43.12%). significantly mediate impact most outcomes except anxiety, frailty not T2D. Conclusion capture stemming risks, be potentially targeted for longevity promotion.

Language: Английский

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Biological age is superior to chronological age in predicting hospital mortality of the critically ill

Internal and Emergency Medicine, Journal Year: 2023, Volume and Issue: 18(7), P. 2019 - 2028

Published: Aug. 28, 2023

Abstract Biological age is increasingly recognized as being more accurate than chronological in determining chronic health outcomes. This study assessed whether biological age, on intensive care unit (ICU) admission, can predict hospital mortality. retrospective cohort study, conducted a tertiary multidisciplinary ICU Western Australia, used the Levine PhenoAge model to estimate each patient’s (also called PhenoAge). Each was calibrated generate regression residual which equivalent unexplained by local context. PhenoAgeAccel dichotomized measure of residuals, and its presence suggested that one biologically older corresponding age. Of 2950 critically ill adult patients analyzed, 291 died (9.9%) before discharge. Both residuals (after regressing age) had significantly better ability differentiate between survivors non-survivors (area under receiver-operating-characteristic curve 0.648 0.654 vs. 0.547 respectively). Being phenotypically one’s associated with an increased risk mortality (PhenoAgeAccel hazard ratio [HR] 1.997, 95% confidence interval [CI] 1.568–2.542; p = 0.001) dose-related fashion did not reach plateau until at least 20-year gap. adverse association remained significant (adjusted HR 1.386, CI 1.077–1.784; 0.011) after adjusted for severity acute illness comorbidities. prevalent among those pre-existing cardiovascular disease, end-stage renal failure, cirrhosis, immune diabetes mellitus, or treated immunosuppressive therapy. common comorbidities, this fully explained comorbidities illness.

Language: Английский

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