The epigenetic clock has developed faster than the iWatch: it can predict biological age from select CpGs, which when compared with chronological age, gives a metric known as Δ-age. The greater the difference, the greater the acceleration of epigenetic age, which indicates variation in the rate of senescence between people. To understand this variation and given that stress shortens our lives, an international team of scientists have now investigated how stress influences the ticking of the epigenetic clock.
Here’s what they found by analyzing blood samples from an urban African American cohort (n=392) on beadchip arrays after controlling for both life-style and blood cell type composition:
- Cumulative lifetime stress (and not childhood maltreatment or current stress alone) is behind accelerated epigenetic aging.
- Accelerated epigenetic aging is driven by personal life stressors that affect the individual, rather than the stress of those around you, while also growing increasingly apparent with older chronological age.
Interestingly, the effect of stress on the clock was blunted in individuals abused as children, which hinted at glucocorticoids as a potential mechanism due to the secreted hormone’s pervasive role in stress signaling. Of the 353 epigenetic clock CpGs, a striking 24% (85) were located in glucocorticoid response elements.
These observations led the team to their next round of experiments where they examined the before and after effects of a glucocorticoid receptor agonist (dexamethasone) in an independent sample using beadchip arrays for DNA methylation (n=124) and RNA expression (n=297). This revealed that:
- Dexamethasone induced dynamic changes at 31% (110/353) of epigenetic clock CpGs.
- It also altered transcription at 82% (139/170) of the genes in the neighborhood of epigenetic clock CpGs.
- A disease enrichment analysis of these genes revealed enrichment for aging-related diseases, including coronary artery disease, arteriosclerosis, and leukemia.
Ultimately, this research begins to unravel the mechanisms behind how chronic stress leads to accelerated aging and disease risk while also providing some interesting observations towards our quest for the fountain of youth.
Take some time to check out the effect of stress on senescence in Genome Biology, December 2015