An integrative module analysis of DNA methylation landscape in aging.

ABSTRACT: To investigate the molecular mechanism of aging, the combination of module analysis and DNA methylation data was used to detect dynamically controlled modules for aging. Multiple differential expression networks (DENs) were constructed based on the microarray profiles across different aging groups (<70 years, 70-80 years, and >80 years). Next, a module-based approach was utilized to extract the common candidate modules across all age groups. We used Module Connectivity Dynamic Score (MCDS) to quantify the connectivity change of the common modules among the different age groups. Functional analyses were implemented for the genes in the common modules to further identify the significant biological processes. A total of two DENs were constructed. Overall 657 informative genes were screened out. When false discovery rate (FDR) was set as 0.05, we found that 148 modules were significant. Only 1 significant 2-differential modules (DMs) (module 493) with dynamic changes was discovered. Significantly, the genes in the module 493 participated in 7 significant pathways, including pentose phosphate pathway, carbon metabolism, and citrate cycle (TCA cycle). In conclusion, pathway functions [pentose phosphate pathway, carbon metabolism, citrate cycle (TCA cycle), chromosomal instability, ateroid biosynthesis, PPAR signaling pathway, and immune response] may serve as potential therapeutic targets in aging.

SUBMITTER: Li G 

PROVIDER: S-EPMC6447821 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature