We’re living in the information age―the age of supercomputers, big data, and machine learning―and the epigenetics field is capitalizing on these capabilities. New research from the lab of Anne Brunet at Stanford University harnesses the power of the ‘information age’ to provide insight on the ‘inflammation age’―that is, changes in the epigenetic landscape that lead to increases in inflammation as we get older.
We know that epigenetics plays a definitive role in aging, but prior research had failed to cover epigenomic and transcriptomic changes across tissue types during aging. In order to properly investigate this, the talented team collected samples from mice during youth (3 months), middle age (12 months) and old age (29 months), and gathered four different tissue types known to undergo age-related degeneration: heart, liver, cerebellum, and olfactory bulb. They additionally derived primary cultures of neural stem cells for all three ages of mice. For each tissue type and cell line, they generated transcriptomic maps using RNA-seq, and utilized ChIP-seq to assay H3K27ac, which is enriched at active enhancers, and H3K4me3, which is enriched at promoters. This savvy Stanford group then utilized machine learning analyses of chromatin states to predict transcriptional changes during aging. Here’s what they found:
- Changes in age-related chromatin states are predictive of concurrent transcriptional changes
- Predictive histone profiles include changes in the amount of H3K27ac at enhancers as well as changes in the breadth of H3K4me3 domains
- Immune-related pathways are misregulated at the chromatin and transcriptome level during aging
- There is an up-regulation of the interferon response pathway, potentially caused by re-activation of transposable elements
- They identified several families of transposable elements whose transcripts were up-regulated during aging
- Age-related transcriptome changes seen in mice are conserved in other vertebrates including the African killfish, rats, and humans
Perhaps many of us need no additional reminders that inflammation and aging go hand in hand, but by identifying common epigenetic signatures in aging tissue and the hallmarks of young tissues, the authors bring us closer to effectively treating age-related dysfunction.
Until we get there, grab your reading glasses and check out the full article in Genome Research, March 2019.