Blood DNA methylation in older people with dementia

- Posted by

Neurodegenerative diseases mainly affect the elderly. These diseases are characterized by the production of aggregates of misfolded, mislocalized proteins. One might think that there is a causal link between aging and this production of abnormal proteins. This link could be related to DNA methylation or genome instability, two phenomena associated with aging and having an impact on protein production. enter image description here The strong effect of age on DNA methylation levels has been known since the late 1960s. Horvath hypothesized that DNA methylation age measures the cumulative effect of a system epigenetic maintenance.

The sources of genome instability have only recently begun to be elucidated. Since endogenous DNA damage (caused by metabolism) is very common, occurring on average more than 60,000 times per day in human cell genomes, any reduced DNA repair is likely an important source genome instability.

For example, dogs lose about 3.3% of their heart muscle cell DNA every year, while humans lose about 0.6% of their heart muscle DNA every year. These figures are close to the ratio of the maximum longevities of the two species (120 years against 20 years, a ratio of 6/1).

DNA methylation could therefore explain the interindividual variability observed in the development of dementia and cognitive disorders. However, the importance of epigenetic alterations in explaining their etiology is unclear because little is known about when they appear.

In a recent publication, the authors longitudinally using Illumina MethylationEPIC chips, analyzed the peripheral blood methylomes of cognitively healthy older adults (>70 years), some of whom later developed dementia while others remained healthy. The methylome is the set of nucleic acid methylation modifications in the genome of an organism or in a particular cell.

The scientists tested 34 people at the pre-diagnosis stage and at a 4-year follow-up at the post-diagnosis stage (total n=68).

Their results show multiple alterations in DNA methylation linked to dementia status, particularly at differentially methylated regions.

The authors also validate the previously reported epigenetic alteration of HOXB6 and PM20D1 (associated with Alzheimer's disease). They show that most of these regions are already altered at the pre-diagnosis stage of people who then develop dementia.

In conclusion, their observations suggest that dementia-associated epigenetic patterns are already present before diagnosis, and therefore may be important in the design of epigenetic biomarkers for peripheral tissue-based disease detection.

In addition, one could imagine that the therapeutic use of Yamanaka factors (Myc, Oct3/4, Sox2 and Klf4) could lead to an improvement in this type of pathology. This has recently been recently tested using lines of mice genetically modified to produce the Yamanaka factors.

It seems considerably more difficult to perform successful gene therapy on humans, while people with dementia often have a very low life expectancy at the time of their diagnosis.

Please, help us continue to provide valuable information: