EPIGENETIC CLOCK PREDICTS LIFE EXPECTANCY

UCLA-led study shows 5 percent of population ages faster, faces shorter lifespan

The rate of your biological clock influences how long you'll live.

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.

Newswise, October 3, 2016 — UCLA geneticist Steve Horvath led a team of 65 scientists in seven countries to record age-related changes to human DNA, calculate biological age 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 principal investigator Horvath, a professor of human genetics and biostatistics at UCLA’s David Geffen School of Medicine 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.

“We were stunned to see that the epigenetic clock was able to predict the lifespans of Caucasians, Hispanics and African-Americans,” said first author Brian Chen, a postdoctoral fellow at the National Institute on Aging.

“This rang true even after adjusting for traditional risk factors like age, gender, smoking, body-mass index, disease history and blood cell counts.”

The group’s findings, however, 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, Peter and Joe, both smoke to deal with high stress. Peter’s epigenetic aging rate ranks in the top 5 percent, while Joe’s aging rate is average. The likelihood of Peter dying within the next 10 years is 75 percent compared to 60 percent for Joe.

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 of 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,” said Kiel.

“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.

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

“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, said Horvath.

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

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

ADVANCEMENTS IN AGING RESEARCH TARGET MULTIPLE AGE-RELATED DISEASES

Newswise, August 22, 2016– The University of Alabama at Birmingham, along other members of the Geroscience Network, has published six manuscripts that map strategies for taking new drugs that target processes underlying aging into clinical trials.

Researchers believe these agents hold promise for treating multiple age-related diseases and disabilities. The articles appear today in The Journals of Gerontology: Series A – Biological Sciences and Medical Sciences.

The Geroscience Network, formed by Steven Austad, Ph.D., distinguished professor and chair ofUAB’s Department of Biology in the College of Arts and Sciences; James Kirkland, M.D., Ph.D., director of the Mayo Clinic Robert and Arlene Kogod Center on Aging; and Nir Barzilai, M.D., Albert Einstein College of Medicine, consists of 18 academic aging centers, along with the participation of more than 100 investigators from across the United States and Europe. The network is funded by the National Institutes of Health.

“Aging is not just an abstract and intriguing biological problem,” Austad said.

“It is the No. 1 cause of death and disability in today’s world. Its threat is very significant, because aging is a major risk factor in a host of other serious diseases and health issues.

The Geroscience Network seeks to combine research from a number of institutions to address this ever-growing challenge.”

“Aging is the largest risk factor for most chronic diseases, including stroke, heart disease, cancer, dementias, osteoporosis, arthritis, diabetes, metabolic syndrome, blindness and frailty,” Kirkland said.

“Recent research suggests that aging may actually be a modifiable risk factor. The goal of our network’s collaborative efforts is to accelerate the pace of discovery in developing interventions to delay, prevent or treat these conditions as a group, instead of one at a time.”

Austad is the senior author on the manuscript “Evaluating Health Span in Preclinical Models of Aging and Disease: Guidelines, Challenges, and Opportunities for Geroscience,” which assesses how research animals can be best employed to guide the development of therapies that counteract aging processes.

Kirkland is senior author on manuscripts that explore the challenges of developing aging interventions:
•“Barriers to the Preclinical Development of Therapeutics That Target Aging Mechanisms”
•“Frameworks for Proof-of-Concept Clinical Trials of Interventions That Target Fundamental Aging Processes”

The first manuscript summarizes discussions held at a 2014 Geroscience Network retreat.

While research efforts have successfully identified new drugs that extend lifespan in animals, the authors discuss the need to develop a consistent preclinical pipeline for drug development that focuses on best practices for drug discovery, development of lead compounds, translational preclinical biomarkers, funding and support for preclinical studies, and integration between researchers and clinicians.

In the second manuscript, the researchers acknowledge that aging therapies may hold “great promise” for enhancing the health of a wide population, with clinical trials’ being a critical step for translating therapies from animals into humans.

The manuscript is built on the outcomes of an international meeting funded through the National Institutes of Health R24 Geroscience Network.

The other manuscripts published are:
•“Strategies and Challenges in Clinical Trials Targeting Human Aging”
•“Resilience in Aging Mice”
•“Moving Geroscience Into Uncharted Waters”

Felipe Sierra, Ph.D., of the National Institute on Aging and a member of the Geroscience Network, describes the potential impact of aging discoveries in his manuscript, “Moving Geroscience Into Uncharted Waters.”

Sierra said, “In addition to the direct health issues, it has been calculated that care for the elderly currently accounts for 43 percent of the total health care spending in the U.S., or approximately $1 trillion a year, and this number is expected to rise as baby boomers reach retirement age.

“Reducing these costs is critical for the survival of society as we know it, and a 2013 paper by Dana Goldman and colleagues calculated that a modest increase in lifespan and health span (2.2 years) could reduce those expenses by $7 trillion by 2050.”

“While significant work has already been accomplished, there is much more to be done as we focus on translating findings into practice,” Kirkland said.

“The Geroscience Network is a collaborative way to overcome barriers and move us closer to our shared goal of increasing health span — the healthy, independent years of life for the elderly.”

In addition to UAB, members of the Geroscience Network are Albert Einstein College of Medicine, Buck Institute for Research on Aging, Harvard University, the Mayo Clinic, Johns Hopkins University, National Institute on Aging, the Scripps Research Institute, Stanford University, the University of Arkansas, the University of Connecticut, the University of Michigan, the University of Minnesota, the University of Oklahoma, the University of Texas Health Science Center San Antonio, the University of Southern California, the University of Washington and Wake Forest University, as well as members from other institutions across the U.S. and Europe.

This work was supported by the National Institutes of Health, the Paul Glenn Foundation, Nathan Shock Centers of Excellence for the Biology of Aging, the Connor Group, and the Noaber and Ted Nash foundations. Additional acknowledgements include the contributions of the basic researchers and clinicians engaged in research on mechanisms of aging and care of the elderly in the five retreats supported by the R24 grant from the National Institute on Aging, as well as a workshop on resilience and aging supported by the National Institute on Aging.

About UAB
Known for its innovative and interdisciplinary approach to education at both the graduate and undergraduate levels, the University of Alabama at Birmingham is an internationally renowned research university and academic medical center and the state of Alabama’s largest employer, with some 23,000 employees and an economic impact exceeding $5 billion annually on the state. The five pillars of UAB’s mission include education, research, patient care, community service and economic development. UAB: Knowledge that will change your world. Learn more at www.uab.edu.

MAYO CLINIC, COLLABORATORS WORKING TO ADVANCE AGING RESEARCH

 Newswise, August 22, 2016— Mayo Clinic, along with other members of the Geroscience Network, has published six manuscripts that map strategies for taking new drugs that target processes underlying aging into clinical trials. Researchers believe that these agents hold promise for treating multiple age-related diseases and disabilities.

The articles appear today in The Journals of Gerontology: Series A – Biological Sciences and Medical Sciences.

The Geroscience Network, formed by James Kirkland, M.D., Ph.D., director of the Mayo Clinic Robert and Arlene Kogod Center on Aging; Steve Austad, Ph.D., University of Alabama at Birmingham; and Nir Barzilai, M.D., Albert Einstein College of Medicine, consists of 18 academic aging centers, along with the participation of more than 100 investigators from across the U.S. and Europe.

The network is funded by the National Institutes of Health.

“Aging is the largest risk factor for most chronic diseases, including stroke, heart disease, cancer, dementias, osteoporosis, arthritis, diabetes, metabolic syndrome, blindness and frailty,” says Dr. Kirkland.

“Recent research suggests that aging may actually be a modifiable risk factor. The goal of our network’s collaborative efforts is to accelerate the pace of discovery in developing interventions to delay, prevent or treat these conditions as a group, instead of one at a time.”

Dr. Kirkland is senior author on manuscripts that explore the challenges of developing these interventions:

• “Barriers to the Preclinical Development of Therapeutics That Target Aging Mechanisms”
• “Frameworks for Proof-of-Concept Clinical Trials of Interventions That Target Fundamental Aging Processes”

The first manuscript summarizes discussions held at a 2014 Geroscience Network Retreat.

While research efforts have successfully identified new drugs that extend lifespan in animals, the authors discuss the need to develop a consistent preclinical pipeline for drug development that focuses on best practices for drug discovery, development of lead compounds, translational preclinical biomarkers, funding and support for preclinical studies, and integration between researchers and clinicians.

In the second manuscript, Dr. Kirkland and others acknowledge that aging therapies may hold “great promise” for enhancing the health of a wide population, with clinical trials being a critical step for translating therapies from animals into humans.

The manuscript is built on the outcomes of an international meeting funded through the National Institutes of Health R24 Geroscience Network.

The other manuscripts published are:

• “Strategies and Challenges in Clinical Trials Targeting Human Aging”
• “Resilience in Aging Mice”
• “Evaluating Health Span in Preclinical Models of Aging and Disease: Guidelines, Challenges, and Opportunities for Geroscience”
• “Moving Geroscience Into Uncharted Waters”

Felipe Sierra, Ph.D., of the National Institute on Aging and a member of the Geroscience Network, describes the potential impact of aging discoveries in his manuscript, “Moving Geroscience into Uncharted Waters.”

Dr. Sierra says, “In addition to the direct health issues, it has been calculated that care for the elderly currently accounts for 43 percent of the total health care spending in the US, or approximately 1 trillion dollars a year, and this number is expected to rise as baby boomers reach retirement age.

Reducing these costs is critical for the survival of society as we know it, and a 2013 paper by Dana Goldman and colleagues calculated that a modest increase in lifespan and healthspan (2.2 years) could reduce those expenses by 7 trillion dollars by 2050.”

“While significant work has already been accomplished, there is much more to be done as we focus on translating findings into practice,” says Dr. Kirkland.

“The Geroscience Network is a collaborative way to overcome barriers and move us closer to our shared goal of increasing healthspan – the healthy, independent years of life for the elderly.”

Other authors in the manuscripts published in the Journal of Gerontology’s special issue are Jordan Miller, Ph.D., Shahrukh Hashmi, M.D., and Michael Stout, Ph.D. of Mayo Clinic; Jamie Justice, Ph.D. of University of Colorado Boulder and Wake Forest School of Medicine; John Newman, Ph.D. of the University of California San Francisco; Jeffrey Halter, M.D. of the University of Michigan; Steve Austad, Ph.D. of the University of Alabama at Birmingham; Nir Barzilai, M.D., Derek Huffman, Ph.D., and Sofiya Milman, M.D. of Albert Einstein College of Medicine; Christin Burd, Ph.D. of The Ohio State University; Matthew Gill, Ph.D., Laura Niedernhofer, M.D., Ph.D., and Paul Robbins, Ph.D. of The Scripps Research Institute.

In addition to Mayo Clinic, members of the Geroscience Network are Albert Einstein College of Medicine, Buck Institute for Research on Aging, Harvard University, Johns Hopkins University, National Institute on Aging, the Scripps Research Institute, Stanford University, the University of Alabama at Birmingham, the University of Arkansas, the University of Connecticut, the University of Michigan, the University of Minnesota, the University of Oklahoma, the University of Texas Health Science Center San Antonio, the University of Southern California, the University of Washington, and Wake Forest University as well as members from other institutions across the U.S. and Europe.

This work was supported by the National Institutes of Health, the Paul Glenn Foundation, Nathan Shock Centers of Excellence for the Biology of Aging, the Connor Group, and the Noaber and Ted Nash foundations. Additional acknowledgements include the contributions of the basic researchers and clinicians engaged in research on mechanisms of aging and care of the elderly in the five retreats supported by the R24 grant from the National Institute on Aging, as well as a workshop on resilience and aging supported by the National Institute on Aging.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to clinical practice, education and research, providing expert, whole-person care to everyone who needs healing. For more information, visit http://www.mayoclinic.org/about-mayo-clinic orhttp://www.newsnetwork.mayoclinic.org/.