GrimAge Clock Improves Prediction of Healthy Lifespan

Researchers at UC Los Angeles have developed an aging clock. This biomarker, known as DNA methylation GrimAge (DNAmGrimAge), allows one to predict lifespan and healthspan, and to test potential interventions that may slow or perhaps even reverse biological aging.

Aging clocks, or epigenetic clocks, are biomarkers based on DNA methylation (DNAm) that track aging. Intended to measure biological age, epigenetic clocks predict age-related health issues. See our previous posts on aging clocks.

“When it comes to predicting lifespan, GrimAge is 18% more accurate than calendar age and 14% better than previously-described epigenetic biomarkers,” explain researchers Ake Lu and Steve Horvath in a press release.

“With regards to predicting time to coronary heart disease, GrimAge is 61% more accurate than chronological age and 46% better than previously-reported epigenetic biomarkers. In spite of this significant enhancement however, it must be noted that neither age nor DNAm GrimAge is particularly good at predicting time to heart disease.”

Using samples from thousands of individuals, the researchers demonstrated that DNAm GrimAge stands out among existing epigenetic clocks. It has greater predictive ability for time-to-death, time-to-coronary heart disease, time-to-cancer, age-at-menopause, and fatty liver/excess visceral fat levels.

The findings are reported in a research paper published in Aging. DNAm GrimAge shows the expected relationship with lifestyle factors including healthy diet. It measures an individual's risk of mortality by analyzing positions on the DNA where methyl groups change with age.

“Over a thousand such specific positions are monitored by DNAmGrimAge which combines these values into an age estimate called GrimAge,” explains Lu in the press release. “If you fall within the top 5 percent of the fastest ‘agers’, your risk of death is sadly more than twice that of the average person. If however, you are within the bottom 5 percent of slowest agers, then happily, your risk is only half that of the average person.”

The DNA positions used by GrimAge are those that track the levels of blood proteins that are known to be associated with health, as well as those that are associated with smoking history.

“At this point, we don’t have any evidence that it’s clinically useful, because there are big error bars,” said Horvath as reported by MIT Technology Review. But the researchers are getting close to “answering the question that hangs over us all - and determining whether there is anything we can do to change the answer.”

In fact, Horvath hopes that aging clocks will soon be precise enough to reflect changes in lifestyle and behavior. MIT Technology review notes that there are important implications for the life insurance sector.

The researchers note that, despite their obvious strengths, DNAm-based biomarkers are expected to complement rather than replace traditional clinical biomarkers for aging such as blood glucose or blood pressure measurements. However, the conclusion of the abstract of the research paper is that “epigenetic biomarkers are expected to find many applications including human anti-aging studies.”