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

Nature Aging, Journal Year: 2022, Volume and Issue: 2(7), P. 644 - 661

Published: July 15, 2022

Language: Английский

---

Signaling pathways in rheumatoid arthritis: implications for targeted therapy

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 17, 2023

Abstract Rheumatoid arthritis (RA) is an incurable systemic autoimmune disease. Disease progression leads to joint deformity and associated loss of function, which significantly impacts the quality life for sufferers adds losses in labor force. In past few decades, RA has attracted increased attention from researchers, abnormal signaling pathways are a very important research field diagnosis treatment RA, provides evidence understanding this complex disease developing novel RA-linked intervention targets. The current review intends provide comprehensive overview including general introduction disease, historical events, epidemiology, risk factors, pathological process, highlight primary progress various molecular mechanisms, genetic epigenetic summarize most recent developments identifying new inhibitors treating RA. therapeutic interventions approved drugs, clinical pre-clinical cutting-edge technologies. These will hopefully drive strategically targeted therapies hope ideas options future.

Language: Английский

---

Epigenetic clock: A promising biomarker and practical tool in aging

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 81, P. 101743 - 101743

Published: Oct. 4, 2022

Language: Английский

---

WHO working definition of vitality capacity for healthy longevity monitoring

The Lancet Healthy Longevity, Journal Year: 2022, Volume and Issue: 3(11), P. e789 - e796

Published: Nov. 1, 2022

Language: Английский

---

Association of Pace of Aging Measured by Blood-Based DNA Methylation With Age-Related Cognitive Impairment and Dementia

Neurology, Journal Year: 2022, Volume and Issue: 99(13)

Published: July 6, 2022

Background and Objectives

DNA methylation algorithms are increasingly used to estimate biological aging; however, how these proposed measures of whole-organism aging relate in the brain is not known. We data from Alzheimer9s Disease Neuroimaging Initiative (ADNI) Framingham Heart Study (FHS) Offspring Cohort test association between blood-based cognitive impairment dementia older adults.

Methods

tested 3 "generations" age (first generation: Horvath Hannum clocks; second PhenoAge GrimAge; third DunedinPACE, Dunedin Pace Aging Calculated Epigenome) against following ADNI: clinical diagnosis mild impairment, scores on Alzheimer disease (AD) / related dementias (ADRD) screening tests (Alzheimer9s Assessment Scale, Mini-Mental State Examination, Montreal Cognitive Assessment), (Rey Auditory Verbal Learning Test, Logical Memory test, Trail Making Test). In an independent replication FHS Cohort, we further longitudinal risk developing dementia.

Results

ADNI (N = 649 individuals), first-generation (Horvath clocks) second-generation (PhenoAge GrimAge) were consistently associated with By contrast, a third-generation measure aging, was (beta [95% CI] 0.28 [0.08–0.47]), poorer disease/ADRD [Robust SE] −0.10 [0.04] 0.08[0.04]), −0.12 0.10 [0.03]). The faster pace as measured by confirmed analysis 2,264 individuals, hazard ratio 1.27 [1.07–1.49]).

Discussion

Third-generation could prove valuable for measuring differences individuals rate at which they their decline, evaluating interventions slow aging.

Language: Английский

---

Physical activity is associated with slower epigenetic ageing—Findings from the Rhineland study

Aging Cell, Journal Year: 2023, Volume and Issue: 22(6)

Published: April 10, 2023

Abstract Epigenetic ageing, i.e., age‐associated changes in DNA methylation patterns, is a sensitive marker of biological major determinant morbidity and functional decline. We examined the association physical activity with epigenetic ageing role immune function cardiovascular risk factors mediating this relation. Moreover, we aimed to identify novel molecular processes underlying between ageing. analysed cross‐sectional data from 3567 eligible participants (mean age: 55.5 years, range: 30–94 54.8% women) Rhineland Study, community‐based cohort study Bonn, Germany. Physical components (metabolic equivalent (MET)‐Hours, step counts, sedentary, light‐intensity moderate‐to‐vigorous intensity activities) were recorded accelerometers. was measured Illumina HumanMethylationEPIC BeadChip. age acceleration (Hannum's age, Horvath's PhenoAge GrimAge) calculated based on published algorithms. The relation multivariable regression, while structural equation modeling used for mediation analysis. conducted an epigenome‐wide across 850,000 CpG sites. After adjustment sex, season, education, smoking, cell proportions batch effects, (step MET‐Hours %time spend non‐linearly associated slower part through its beneficial effects health. Additionally, identified 12 7 CpGs spent activities, respectively ( p < 1 × 10 −5 ). Our findings suggest that regular slows by counteracting immunosenescence lowering risk.

Language: Английский

---

Interdisciplinary fetal-neonatal neurology training applies neural exposome perspectives to neurology principles and practice

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 15, 2024

An interdisciplinary fetal-neonatal neurology (FNN) program over the first 1,000 days teaches perspectives of neural exposome that are applicable across life span. This curriculum strengthens neonatal neurocritical care, pediatric, and adult training objectives. Teaching at maternal-pediatric hospital centers optimally merges reproductive, pregnancy, pediatric approaches to healthcare. Phenotype–genotype expressions health or disease pathways represent a dynamic developmental time. The science uncertainty applied FNN re-enforces importance shared clinical decisions minimize bias reduce cognitive errors. Trainees select mentoring committee participants will maximize their learning experiences. Standardized questions oral presentations monitor educational progress. Master doctoral defense preparation competitive research funding can be goals for specific individuals. principles practice offer an understanding gene–environment interactions recognizes effects reproductive on maternal-placental-fetal triad, neonate, child, adult. Pre-conception prenatal adversities potentially diminish life-course brain health. Endogenous exogenous toxic stressor interplay (TSI) alters through maladaptive neuroplasticity. Developmental disorders epilepsy primarily expressed during days. Communicable noncommunicable illnesses continue interact with express diverse neurologic lifespan, particularly critical/sensitive time periods adolescence senescence. Anomalous destructive fetal neuropathologic lesions change this developmental-aging continuum. integrated placental, neonatal, childhood, offers perspective exposome. Exosome promises improved monitoring drug delivery starting pregnancy. origins anticipate diagnoses interventions benefit successive generations. Addressing care disparities in Global South high-income country medical deserts require constructive dialogue among stakeholders achieve equity. Population policies capital strategy reduces global burden diseases by applying practice. integrative approach prolong survival quality persons lifespan confronted neurological disorders.

Language: Английский

---

Sex-specific mechanisms in vascular aging: exploring cellular and molecular pathways in the pathogenesis of age-related cardiovascular and cerebrovascular diseases

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Language: Английский

---

The association of epigenetic clocks in brain tissue with brain pathologies and common aging phenotypes

Neurobiology of Disease, Journal Year: 2021, Volume and Issue: 157, P. 105428 - 105428

Published: June 19, 2021

Epigenetic clocks are calculated by combining DNA methylation states across select CpG sites to estimate biologic age, and have been noted as the most successful markers of aging date. Yet, limited research has considered epigenetic in brain tissue. We used dorsolateral prefrontal cortex specimens from 721 older participants Religious Orders Study Rush Memory Aging Project, calculate age using four established clocks: Hannum, Horvath, PhenoAge, GrimAge, a new Cortical clock. The were trained blood samples (Hannum, GrimAge) or 51 human tissue cell types (Horvath); recent clock is first postmortem cortical Participants recruited beginning 1994 (Religious Study) 1997 (Memory Project), followed annually with questionnaires clinical evaluations; obtained for 80–90% participants. Mean at death was 88.0 (SD 6.7) years. linear regression, logistic mixed models, examine relations ages neuropathologic phenotypes, controlling chronologic sex, education, depressive symptomatology. PhenoAge related pathologic diagnosis Alzheimer's disease (AD), well Aβ load (a hallmark pathology disease). However, associations substantially stronger than other clocks; example, each standard deviation (SD) increase approximately 30% greater likelihood AD (all p < 0.05), while SD 90% (odds ratio = 1.91, 95% confidence interval 1.38, 2.62). Moreover, significantly (eg, mean tau tangle density, 0.003), odds neocortical Lewy body (for 2.00, 1.27, 3.17), although no cerebrovascular neuropathology. only associated phenotypes examined, dementia cognitive decline (5 specific systems, global measure averaging 17 tasks) Parkinsonian signs. Overall, our findings provide evidence critical necessity bespoke advancing understand, eventually prevent, neurodegenerative diseases aging.

Language: Английский

---

Accelerated epigenetic aging mediates link between adverse childhood experiences and depressive symptoms in older adults: Results from the Health and Retirement Study

SSM - Population Health, Journal Year: 2022, Volume and Issue: 17, P. 101071 - 101071

Published: March 1, 2022

Adverse childhood experiences (ACEs) increase risk for depression at subsequent ages and have been linked to accelerated biological aging. We hypothesize that epigenetic aging may partially mediate the link between ACEs depression. This study examines 3 three second-generation measures (viz., GrimAge, PhenoAge, DunedinPoAm38) as mediators of depressive symptoms in older adulthood. utilize structural equation modeling assess mediation Health Retirement Study (N = 2672). Experiencing is significantly associated with an GrimAge a faster pace via DunedinPoAm38. Having DunedinPoAm38 were also more symptoms. PhenoAge was not only experiencing ACEs. These associations reduced by socioeconomic lifestyle factors, including obesity substance use. explained 9 14% association adult symptoms, 2 7% Findings indicate aging, measured DunedinPoAm38, Americans. show these portion Epigenetic represent physiological mechanism underlying early life adversity Weight maintenance use are potentially important areas intervention.

Language: Английский

---