Epigenetic Clock Predicts Life Expectancy

Summary: Researchers have developed an ‘epigenetic clock’ that calculates the biological age of a person from a blood sample and can estimate the person’s life span.

Source: UCLA.

New research finds 5 percent of population ages faster and faces shorter lifespan.

Why do some people lead a perfectly healthy lifestyle yet still die young? A new international study suggests that the answer lies in our DNA.

UCLA geneticist Steve Horvath led a team of 65 scientists in seven countries to record age-related changes to human DNA, calculate the biological age of blood and estimate a person’s lifespan. A higher biological age — regardless of chronological age — consistently predicted an earlier death.

The findings are published in today’s edition of the journal Aging.

“Our research reveals valuable clues into what causes human aging, marking a first step toward developing targeted methods to slow the process,” said Horvath, the principal investigator and a professor of human genetics and biostatistics at the David Geffen School of Medicine at UCLA and Fielding School of Public Health.

Drawing on 13 sets of data, including the landmark Framingham Heart Study and Women’s Health Initiative, a consortium of 25 institutions analyzed the DNA in blood samples collected from more than 13,000 people in the United States and Europe.

Applying a variety of molecular methods, including an epigenetic clock developed by Horvath in 2013, the scientists measured the aging rates of each individual. The clock calculates the aging of blood and other tissues by tracking methylation, a natural process that chemically alters DNA over time. By comparing chronological age to the blood’s biological age, the scientists used the clock to predict each person’s life expectancy.

“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,” said Brian Chen, the study’s first author and a postdoctoral fellow at the National Institute on Aging.

The group’s findings don’t bode well for everyone.

“We discovered that 5 percent of the population ages at a faster biological rate, resulting in a shorter life expectancy,” Horvath said. “Accelerated aging increases these adults’ risk of death by 50 percent at any age.”

For example, two 60-year-old men both smoke to deal with high stress. The first man’s epigenetic aging rate ranks in the top 5 percent, while the second’s aging rate is average. The likelihood of the first man dying within the next 10 years is 75 percent compared to 60 percent for the second.

The preliminary finding may explain why some individuals die young — even when they follow a nutritious diet, exercise regularly, drink in moderation and don’t smoke.

“While a healthful lifestyle may help extend life expectancy, our innate aging process prevents us from cheating death forever,” Horvath emphasized. “Yet risk factors like smoking, diabetes and high blood pressure still predict mortality more strongly than one’s epigenetic aging rate.”

Scientists have long searched to identify biomarkers for biological age, according to coauthor Dr. Douglas Kiel, a professor at Harvard Medical School and a senior scientist for the Institute for Aging Research at Hebrew SeniorLife.

“In geriatric medicine, we are always struck by the difference between our patients’ chronological age and how old they appear physiologically,” Kiel said. “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.”

The precise role of epigenetic changes in aging and death, however, remains unknown, said coauthor Dr. Themistocles Assimes, an assistant professor of cardiovascular medicine at Stanford University School of Medicine.

Image shows an older lady and man in a yoga pose.

“Do the epigenetic changes associated with chronological aging directly cause death in older people?” Assimes said. “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, he added.

By 2017, according to the World Health Organization, the number of people worldwide over age 65 will outnumber those under age 5 for the first time in recorded history. By 2050, the proportion of the global population over 60 will double from 11 to 22 percent. Many countries will be ill-prepared to keep pace with the high costs associated with disease and disability as more people live longer, Horvath said.

“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.” Horvath said. “The epigenetic clock would allow scientists to quickly evaluate the effect of anti-aging therapies in only three years.”

ABOUT THIS GENETICS AND AGING RESEARCH ARTICLE

The University of California has applied for a provisional patent on the epigenetic clock.

Source: Elaine Schmidt – UCLA
Image Source: NeuroscienceNews.com image is adapted from the UCLA press release.
Original Research: Abstract for “DNA methylation-based measures of biological age: meta-analysis predicting time to death” by Brian H. Chen, Riccardo E. Marioni, Elena Colicino, Marjolein J. Peters, Cavin K. Ward-Caviness, Pei-Chien Tsai, Nicholas S. Roetker, Allan C. Just, Ellen W. Demerath, Weihua Guan, Jan Bressler, Myriam Fornage, Stephanie Studenski, Amy R. Vandiver, Ann Zenobia Moore, Toshiko Tanaka, Douglas P. Kiel, Liming Liang, Pantel Vokonas, Joel Schwartz, Kathryn L. Lunetta, Joanne M. Murabito, Stefania Bandinelli, Dena G. Hernandez, David Melzer, Michael Nalls, Luke C. Pilling, Timothy R. Price, Andrew B. Singleton, Christian Gieger, Rolf Holle, Anja Kretschmer, Florian Kronenberg, Sonja Kunze, Jakob Linseisen, Christine Meisinger, Wolfgang Rathmann, Melanie Waldenberger, Peter M. Visscher, Sonia Shah, Naomi R. Wray, Allan F. McRae, Oscar H. Franco, Albert Hofman, André G. Uitterlinden, Devin Absher, Themistocles Assimes, Morgan E. Levine, Ake T. Lu, Philip S. Tsao, Lifang Hou, JoAnn E. Manson, Cara L. Carty, Andrea Z. LaCroix, Alexander P. Reiner, Tim D. Spector, Andrew P. Feinberg, Daniel Levy, Andrea Baccarelli, Joyce van Meurs, Jordana T. Bell, Annette Peters, Ian J. Deary, James S. Pankow, Luigi Ferrucci, and Steve Horvath in Aging. Published online September 28 2016 doi:Not available

UCLA. “Epigenetic Clock Predicts Life Expectancy.” NeuroscienceNews. NeuroscienceNews, 28 September 2016.
<http://neurosciencenews.com/epigenetics-life-expectancy-5147/&gt;.

Abstract

DNA methylation-based measures of biological age: meta-analysis predicting time to death

Estimates of biological age based on DNA methylation patterns, often referred to as “epigenetic age”, “DNAm age”, have been shown to be robust biomarkers of age in humans. We previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, we expanded our original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, we examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality. All considered measures of epigenetic age acceleration were predictive of mortality (p≤8.2×10-9), independent of chronological age, even after adjusting for additional risk factors (p<5.4×10-4), and within the racial/ethnic groups that we examined (non-Hispanic whites, Hispanics, African Americans). Epigenetic age estimates that incorporated information on blood cell composition led to the smallest p-values for time to death (p=7.5×10-43). Overall, this study a) strengthens the evidence that epigenetic age predicts all-cause mortality above and beyond chronological age and traditional risk factors, and b) demonstrates that epigenetic age estimates that incorporate information on blood cell counts lead to highly significant associations with all-cause mortality.

“DNA methylation-based measures of biological age: meta-analysis predicting time to death” by Brian H. Chen, Riccardo E. Marioni, Elena Colicino, Marjolein J. Peters, Cavin K. Ward-Caviness, Pei-Chien Tsai, Nicholas S. Roetker, Allan C. Just, Ellen W. Demerath, Weihua Guan, Jan Bressler, Myriam Fornage, Stephanie Studenski, Amy R. Vandiver, Ann Zenobia Moore, Toshiko Tanaka, Douglas P. Kiel, Liming Liang, Pantel Vokonas, Joel Schwartz, Kathryn L. Lunetta, Joanne M. Murabito, Stefania Bandinelli, Dena G. Hernandez, David Melzer, Michael Nalls, Luke C. Pilling, Timothy R. Price, Andrew B. Singleton, Christian Gieger, Rolf Holle, Anja Kretschmer, Florian Kronenberg, Sonja Kunze, Jakob Linseisen, Christine Meisinger, Wolfgang Rathmann, Melanie Waldenberger, Peter M. Visscher, Sonia Shah, Naomi R. Wray, Allan F. McRae, Oscar H. Franco, Albert Hofman, André G. Uitterlinden, Devin Absher, Themistocles Assimes, Morgan E. Levine, Ake T. Lu, Philip S. Tsao, Lifang Hou, JoAnn E. Manson, Cara L. Carty, Andrea Z. LaCroix, Alexander P. Reiner, Tim D. Spector, Andrew P. Feinberg, Daniel Levy, Andrea Baccarelli, Joyce van Meurs, Jordana T. Bell, Annette Peters, Ian J. Deary, James S. Pankow, Luigi Ferrucci, and Steve Horvath in Aging. Published online September 28 2016 doi:Not available

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