They say ‘Seasons don’t fear the reaper’, and while the festivities of this season certainly favor the reaper, most of us dread the reaper’s favor. Our understanding of how to avoid that favor is now improving, thanks to some new insight from the epigenetic clock-watching lab of Steve Horvath at UCLA.
The epigenetic clock consists of 353 CpG sites on the 450K array, whose DNA methylation levels can be used to predict how long you’ve been on this planet (chronological age). It can also reveal why you don’t feel your age, an insight gained by the Δ-age metric, which is based on the difference between your biological age as predicted by the epigenetic clock and your actual chronological age. When it comes to what makes the clock tick, it is accelerated by stress, as 24% of its CpGs are located in stress hormone (glucocorticoid) response elements.
To gain further insight into the epigenetic clock, this newest analysis by Horvath and team examined 13 different cohorts, consisting of a total of 13,089 people from three different racial/ethnic groups (non-Hispanic whites, Hispanics, African Americans). Here’s what went down:
- They overcame the limitations of the Δ-age metric, which is negatively correlated with chronological age, and developed a measure of epigenetic age acceleration that is uncorrelated with chronological age by using the powers of regression.
- The proportions of circulating blood cells types change with age, and since the epigenetic clock is read from blood cells, it is difficult to know whether the methylation profile truly represents differences within cells or if it simply reflects the shift in blood cell types. The team tackled this burning question by using blood cell counts estimated by the methylation profiles of their data. This revealed distinct types of epigenetic age acceleration measures:
- Intrinsic epigenetic age acceleration is independent of changes in blood cell composition that happen with time. This metric suggests there is a component to age acceleration that is independent of cell type and is a result of truly differential methylation within the cells themselves.
- Extrinsic epigenetic acceleration includes age-related changes in blood cell composition and thus reflects aging of the immune system, which loses protective abilities as it ages. It also includes cell intrinsic changes and offers the best prediction of all-cause mortality.
- First author Brian Chen adds, “Our findings show that the epigenetic clock was able to predict the lifespans of Caucasians, Hispanics and African-Americans in these cohorts, even after adjusting for traditional risk factors like age, gender, smoking, body-mass index and disease history.”
Applying the Epigenetic Clock
Co-author Douglas Kiel shares, “In geriatric medicine, we are always struck by the difference between our patients’ chronological age and how old they appear physiologically. This study validates the use of DNA methylation as a biomarker for biological age. And if we can prove that DNA methylation accelerates aging, we can devise strategies to slow the rate and maximize a person’s years of good health.”
Co-author Themistocles Assimes opines, “Do the epigenetic changes associated with chronological aging directly cause death in older people? Perhaps they merely enhance the development of certain diseases — or cripple one’s ability to resist the progression of disease after it has taken root. Future research is needed to address these questions. Larger studies focused only on cases with well-documented causes of death will help scientists tease out the relationship between epigenetic age and specific diseases.”
Senior author Steve Horvath summarizes, “We discovered that 5 percent of the population ages at a faster biological rate, resulting in a shorter life expectancy. Accelerated aging increases these adults’ risk of death by 50 percent at any age. While a healthful lifestyle may help extend life expectancy, our innate aging process prevents us from cheating death forever, yet risk factors like smoking, diabetes and high blood pressure still predict mortality more strongly than one’s epigenetic aging rate.”
Horvath is left concluding, “We must find interventions that prolong healthy living by five to 20 years. We don’t have time, however, to follow a person for decades to test whether a new drug works. The epigenetic clock would allow scientists to quickly evaluate the effect of anti-aging therapies in only three years.”
Don’t fear the reaper? Go check your timing on the epigenetic clock over at Aging, September 2016