Abstract
DNA methylation patterns have been shown to change throughout the normal aging process. Several studies have found epigenetic aging markers using age predictors, but these studies only focused on blood-specific or tissue-common methylation patterns. Here, we constructed nine tissue-specific age prediction models using methylation array data from normal samples. The constructed models predict the chronological age with good performance (mean absolute error of 5.11 years on average) and show better performance in the independent test than previous multi-tissue age predictors. We also compared tissue-common and tissue-specific aging markers and found that they had different characteristics. Firstly, the tissue-common group tended to contain more positive aging markers with methylation values that increased during the aging process, whereas the tissue-specific group tended to contain more negative aging markers. Secondly, many of the tissue-common markers were located in Cytosine-phosphate-Guanine (CpG) island regions, whereas the tissue-specific markers were located in CpG shore regions. Lastly, the tissue-common CpG markers tended to be located in more evolutionarily conserved regions. In conclusion, our prediction models identified CpG markers that capture both tissue-common and tissue-specific characteristics during the aging process.
Highlights
Aging is often defined as an overall functional decline over time that affects all living organisms [1].In addition, the human aging process is an important health factor that is still not fully explainable, understanding what happens when people age is of great interest [2,3]
We counted the number of occurrence in features from each tissue-specific age predictors. cg22736354 methylation marker is found as common marker of all nine tissue-specific age predictors
This study revealed epigenetic age predictors that reflect the characteristics of DNA methylation and tissue-specific aging mechanisms
Summary
Aging is often defined as an overall functional decline over time that affects all living organisms [1].In addition, the human aging process is an important health factor that is still not fully explainable, understanding what happens when people age is of great interest [2,3]. Many cellular and molecular hallmarks of aging have been discovered, including cellular senescence [4], gene expression changes [5,6], and telomere attrition [7,8,9]. Biological markers of aging involving epigenetic changes have been studied, and DNA methylation has emerged as a promising biomarker of healthy human aging [10]. DNA methylation is considered to be a crucial epigenetic change because it can alter the activity of genes and is a biomarker that has been implicated in various human diseases, including cancer. Many studies revealed that DNA methylation patterns in specific regions have been shown to change along with the aging process [11,12]
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