Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm

eLife, Год журнала: 2020, Номер 9

Опубликована: Май 5, 2020

Biological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of pace are needed as surrogate endpoints trials therapies designed to prevent disease by slowing biological aging. We report a blood-DNA-methylation measure sensitive variation among individuals born same year. first modeled change-over-time 18 biomarkers tracking organ-system across 12 years follow-up n = 954 members Dunedin Study 1972–1973. Rates change each biomarker over ages 26–38 were composited form aging-related decline, termed Pace-of-Aging. Elastic-net regression was used develop DNA-methylation predictor Pace-of-Aging, called DunedinPoAm for Dunedin(P)ace(o)f(A)ging(m)ethylation. Validation analysis cohort studies CALERIE trial provide proof-of-principle single-time-point person’s

Язык: Английский

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A systematic review of biological, social and environmental factors associated with epigenetic clock acceleration

Ageing Research Reviews, Год журнала: 2021, Номер 69, С. 101348 - 101348

Опубликована: Апрель 28, 2021

Aging involves a diverse set of biological changes accumulating over time that leads to increased risk morbidity and mortality. Epigenetic clocks are now widely used quantify aging, in order investigate determinants modify the rate aging predict age-related outcomes. Numerous biological, social environmental factors have been investigated for their relationship epigenetic clock acceleration deceleration. The aim this review was synthesize general trends concerning associations between human these factors. We conducted systematic all available literature included 156 publications across 4 resource databases. compiled list presently existing blood-based clocks. Subsequently, we created an extensive dataset 1300 study findings which were utilized blood tissue subjects assess numeral exposures traits. Statistical analysis possible on 57 such relationships, measured different (Hannum, Horvath, Levine GrimAge). found Hannum, GrimAge tend agree direction effects, but vary size. Body mass index, HIV infection, male sex significantly associated with one or more Acceleration also related mortality, cardiovascular disease, cancer diabetes. Our provide graphical numerical synopsis past decade age estimation research indicate areas where further attention could be focused coming years.

Язык: Английский

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Hallmarks of Health

Cell, Год журнала: 2020, Номер 184(1), С. 33 - 63

Опубликована: Дек. 18, 2020

Язык: Английский

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Telomere Length as a Marker of Biological Age: State-of-the-Art, Open Issues, and Future Perspectives

Frontiers in Genetics, Год журнала: 2021, Номер 11

Опубликована: Янв. 21, 2021

Telomere shortening is a well-known hallmark of both cellular senescence and organismal aging. An accelerated rate telomere attrition also common feature age-related diseases. Therefore, length (TL) has been recognized for long time as one the best biomarkers Recent research findings, however, indicate that TL per se can only allow rough estimate aging hardly be regarded clinically important risk marker pathologies mortality. Evidence obtained other indicators such certain immune parameters, indices epigenetic age, etc., could stronger predictors health status chronic disease. However, despite these issues limitations, remains to very informative in accessing biological age when used along with markers homeostatic dysregulation, frailty index, clock, etc. This review article aimed at describing current state art field discussing recent findings divergent viewpoints regarding usefulness leukocyte estimating human age.

Язык: Английский

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Measuring biological age using omics data

Nature Reviews Genetics, Год журнала: 2022, Номер 23(12), С. 715 - 727

Опубликована: Июнь 17, 2022

Язык: Английский

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Heterogeneous aging across multiple organ systems and prediction of chronic disease and mortality

Nature Medicine, Год журнала: 2023, Номер 29(5), С. 1221 - 1231

Опубликована: Апрель 6, 2023

Язык: Английский

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Biomarkers of aging for the identification and evaluation of longevity interventions

Cell, Год журнала: 2023, Номер 186(18), С. 3758 - 3775

Опубликована: Авг. 1, 2023

Язык: Английский

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Tau Post-translational Modifications: Dynamic Transformers of Tau Function, Degradation, and Aggregation

Frontiers in Neurology, Год журнала: 2021, Номер 11

Опубликована: Янв. 7, 2021

Post-translational modifications (PTMs) on tau have long been recognized as affecting protein function and contributing to neurodegeneration. The explosion of information potential observed PTMs provides an opportunity better understand these in the context homeostasis, which becomes perturbed with aging disease. Prevailing views regard a that undergoes abnormal phosphorylation prior its accumulation into toxic aggregates implicated Alzheimer's disease (AD) other tauopathies. However, may, fact, represent part normal but interrupted catabolism protein. In addition phosphorylation, another forms post-translational modification including (but not limited to), acetylation, ubiquitination, glycation, glycosylation, SUMOylation, methylation, oxidation, nitration. A holistic appreciation how regulate during health are potentially hijacked remains elusive. Recent studies reinforced idea play critical role localization, protein-protein interactions, maintenance levels, modifying aggregate structure. These also provide tantalizing clues possibility neurons actively choose is post-translationally modified, competitive combinatorial ways, achieve broad, cellular programs commensurate distinctive environmental conditions found development, aging, stress, Here, we review describe what currently known about their functional impacts. addition, classify from perspectives electrostatics, stability, all contribute homeostasis. Finally, assess impact solubility aggregation. Tau occupies undoubtedly important position biology neurodegenerative diseases. This aims integrated perspective actively, purposefully, dynamically remodel function, clearance, doing so, hope enable more comprehensive understanding will positively future studies.

Язык: Английский

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The landscape of aging

Science China Life Sciences, Год журнала: 2022, Номер 65(12), С. 2354 - 2454

Опубликована: Сен. 2, 2022

Язык: Английский

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A computational solution for bolstering reliability of epigenetic clocks: implications for clinical trials and longitudinal tracking

Nature Aging, Год журнала: 2022, Номер 2(7), С. 644 - 661

Опубликована: Июль 15, 2022

Язык: Английский

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