Epigenetic variations have been widely described to occur during the aging process. To verify if these modifications are correlated with the inter-individual phenotypic variability of elderly people, we searched for a correlation between global DNA methylation levels and frailty. We found that the global DNA methylation levels were correlated to the frailty status in middle/advanced-aged subjects but not with age. A 7-year follow-up study also revealed that a worsening in the frailty status was associated to a significant decrease in the global DNA methylation levels. These results suggest that the relaxation of the epigenetic control in aging is specifically associated with the functional decline rather than with the chronological age of individuals. Thus, the modifications of DNA methylation, representing a drawbridge between the genetic and the environmental factors affecting the age-related decay of the organism, may play an important role in determining physiological changes over old age.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260357 | PMC |
http://dx.doi.org/10.1007/s11357-011-9216-6 | DOI Listing |
Predicting health trajectories and accurately measuring aging processes across the human lifespan remain profound scientific challenges. Assessing the effectiveness and impact of interventions targeting aging is even more elusive, largely due to the intricate, multidimensional nature of aging-a process that defies simple quantification. Traditional biomarkers offer only partial perspectives, capturing limited aspects of the aging landscape.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Exeter, Exeter, Devon, United Kingdom.
Background: Huntington's disease (HD) is an autosomal dominant condition causing severe neurodegeneration in the striatum and the entorhinal cortex (EC). An epigenome wide association study of DNA methylation in HD by our group, identified potential hypomethylation at the PTGDS gene in the striatum. We aimed to validate this result through pyrosequencing, examining the locus in fine detail, and to assess the signal specificity by profiling multiple neurodegenerative diseases.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Amsterdam UMC, Amsterdam, Netherlands.
Background: The TMEM106B protein is critical for proper functioning of the endolysomal system, which is utilised by all cells to traffic and degrade molecular cargo. Genome-wide association studies identified a haplotype in the TMEM106B gene that is associated with increased risk for Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal lobar degeneration with TAR DNA binding protein inclusions (FTLD-TDP). However, the causal variant that drives the association has thus far remained elusive.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Exeter, Exeter, Devon, United Kingdom.
Background: Psychosis (broadly delusions and hallucinations) has a cumulative disease prevalence of around 40% in Alzheimer's disease (AD). The epigenomic, genomic, and neuropathological data provide powerful evidence that AD+P has a distinct neurobiological profile. Here, we used the weighted gene co-expression network analysis (WGCNA) method to investigate DNA methylation associated with AD+P in the dorsolateral prefrontal cortex of 153 post-mortem brain samples.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Karolinska Institutet, Solna, Sweden.
Background: High age is the biggest risk factor for Alzheimer's disease (AD). Approved drugs that slow down the aging process have the potential to be repurposed for the primary prevention of AD. The aim of our project was to use a reverse translational approach to identify such drug candidates in epidemiological data followed by validation in cell-based models and animal models of aging and AD.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!