Complementary value of molecular, phenotypic, and functional aging biomarkers in dementia prediction

GeroScience, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

Abstract DNA methylation age (MA), brain (BA), and frailty index (FI) are putative aging biomarkers linked to dementia risk. We investigated their relationship combined potential for prediction of cognitive impairment future risk using the ADNI database. Of several MA algorithms, DunedinPACE GrimAge2, associated with memory, were in a composite alongside BA data-driven FI predictive analyses. Pairwise correlations between age- sex-adjusted measures (aMA), aBA, aFI low. outperformed all diagnostic tasks. A model including age, sex, achieved an area under curve (AUC) 0.94 differentiating cognitively normal controls (CN) from patients held-out test set. When clinical (apolipoprotein E ε4 allele count, executive function), aBA predicted 5-year among MCI out-of-sample AUC 0.88. In prognostic model, offered complementary value (both β s 0.50). The tested MAs did not improve predictions. Results consistent across health deficit selection yielding best performance. had stronger adverse effect on prognosis males, while BA’s impact was greater females. Our findings highlight prediction. results support multidimensional view dementia, intertwined biomarkers, prognosis. MA’s limited contribution suggests caution use individual assessment dementia.

Language: Английский

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Editorial: DNA repair and interventions in aging

Frontiers in Aging, Journal Year: 2023, Volume and Issue: 4

Published: Dec. 5, 2023

EDITORIAL article Front. Aging, 05 December 2023Sec. Interventions in Aging Volume 4 - 2023 | https://doi.org/10.3389/fragi.2023.1306463

Language: Английский

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Complementary value of molecular, phenotypic and functional aging biomarkers in dementia prediction

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 24, 2024

Abstract DNA methylation age (MA), brain (BA), and frailty index (FI) are putative aging biomarkers linked to dementia risk. We investigated their relationship combined potential for prediction of stages cognitive impairment future risk using the ADNI database. Of several MA algorithms, DunedinPACE had strongest association with neuropsychological tests was included alongside BA FI in predictive analyses. The pairwise correlations between age- sex-adjusted measures (aDundedinPACE), (aBA), (aFI) were low (all <0.15). In a model including age, sex, aFI, we achieved an area under curve (AUC) 0.95 differentiating cognitively normal controls (CN) from patients held-out test set. best models CN vs. mild (MCI) MCI contained aFI aBA as predictors, out-of-sample AUCs 0.82 0.83 respectively. When clinical (apolipoprotein E ε4 allele count, memory, executive function), predicted 5-year among AUC 0.83. aDunedinPACE did not improve predictions. stronger adverse effect on prognosis males, while BA’s impact greater females. Our findings highlight complementary value prediction. results support multidimensional view dementia, intertwined biomarkers, prognosis. tested MA’s limited contribution suggests caution use individual assessment dementia.

Language: Английский

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Cross-Tissue Comparison of Epigenetic Aging Clocks in Humans

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 19, 2024

Epigenetic clocks are a common group of tools used to measure biological aging - the progressive deterioration cells, tissues and organs. have been trained almost exclusively using blood-based but there is growing interest in estimating epigenetic age less-invasive oral-based (i.e., buccal or saliva) both research commercial settings. However, differentiated cell types across body exhibit unique DNA methylation landscapes age-related alterations methylome. Applying derived from estimate may introduce biases. We tested within-person comparability five tissue types: epithelial, saliva, dry blood spots, buffy coat leukocytes), peripheral mononuclear cells. 284 distinct samples 83 individuals aged 9-70 years. Overall, were significant differences clock estimates versus tissues, with average 30 years observed some clocks. In addition, most exhibited low correlation despite controlling for cellular proportions other technical factors. Our findings indicate that application blood-derived not yield comparable age, highlighting need careful consideration type when age.

Language: Английский

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Magnesium and Longevity

Published: Nov. 1, 2024

Magnesium (Mg) is not prominent among the list of well known anti-aging agents. Yet signs and symptoms aging mimic those Mg deficiency. a required cofactor for over 800 enzymatic reactions (as 2022). This review does correlate status with clinical data on agents linked to longevity. The approach physiologic highlights specific dependent by these longevity biomarkers. Many share common pathways extend healthspan. in synthesis vitamin D melatonin activation five eight B vitamins. It all CYP450 enzymes. directly responsible appropriate methylation proteins DNA, which control epigenome. MTHFR (methylenetetrahydrofolate reductase) 677T allele that compromises present majority Americans. Aberrant predicts severity Covid-19 its persistence into long Covid. silent benefactor may indirectly link agents, but only if viewed context calcium (Ca), i.e., Ca:Mg. Both compete same receptor. To fully exploit sufficient required. pertinent physiology presented.

Language: Английский

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Magnesium and Longevity

Qeios, Journal Year: 2024, Volume and Issue: 6(11)

Published: Nov. 12, 2024

Magnesium (Mg) is not prominent among the list of well known anti-aging agents. Yet signs and symptoms aging mimic those Mg deficiency. required for nearly a thousand enzymatic reactions. This narrative review does correlate status with clinical data on agents linked to longevity. The approach more novel highlights specific dependent physiologic reactions by these longevity biomarkers. Many share common pathways extend healthspan. cofactor in synthesis vitamin D melatonin activation six eight B vitamins. It all CYP450 enzymes. directly responsible appropriate methylation proteins DNA, which control epigenome. MTHFR (methylenetetrahydrofolate reductase) 677T allele that compromises present majority Americans. Aberrant predicts severity Covid-19 its persistence into long Covid. silent benefactor may indirectly link agents, but only if viewed context calcium (Ca), i.e., Ca:Mg. Both compete same receptor. To fully exploit sufficient required. pertinent physiology presented, although cause effect awaits publication supporting data.

Language: Английский

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Integrating epigenetic modification and stem cell therapy strategies: A novel approach for advancing Alzheimer's disease treatment - A literature review.

PubMed, Journal Year: 2024, Volume and Issue: 4(3), P. e935 - e935

Published: Dec. 1, 2024

Alzheimer's disease (AD) is the most frequent form of dementia and represents an increasing global burden, particularly in countries like Indonesia, where population has begun to age significantly. Current medications, including cholinesterase inhibitors NMDA receptor antagonists, have modest effects on clinical symptoms early middle stages, but there no curative treatment available so far despite progress. Activating or repressing epigenetic modifications, DNA methylation, histone modification microRNA regulation, appears play important role AD development. These alterations further enact transcriptional changes relevant signature pathologies amyloid-β deposition, tau protein malfunctioning, neuroinflammation, neuronal death. Here, we discuss feasibility targeting these as a new strategy due reversibility epigenetics their ability correct faulty gene expression. We also review combined promise stem cell therapies modulation neurodegeneration, inflammation cognitive decline. This approach may provide multifaceted slow progression, replace lost neurons, restore neural function. Despite challenges, ethical, financial, methodological barriers, ongoing research therapy holds for pioneering AD.

Language: Английский

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