Discovering a "smoking gun" of biological aging | New

For immediate release: February 14, 2019

Boston, MA – According to a Harvard T.H. study, a newly discovered ribosomal DNA clock (rDNA) can be used to accurately determine the chronological and biological age of an individual. Chan School of Public Health. The ribosomal clock is a new biomarker of aging based on rDNA, a segment of the genome that was previously mechanically linked to aging. The ribosomal clock has many potential applications, including the measurement of how exposure to certain pollutants or dietary interventions accelerate or slow the aging of various species, including mice and humans.

"We hope that the ribosomal clock will provide new information on the impact of the environment and personal choices on long-term health," said lead author, Bernardo Lemos, Associate professor of environmental epigenetics. "The determination of biological age is an essential step in understanding the fundamental aspects of aging and developing tools to inform personal and public health choices."

The study was published online in Genome research February 14, 2019.

Aging is presented by organisms as diverse as yeast, worms, flies, mice and humans. Age is also the main risk factor for a multitude of diseases, including neurological diseases, cardiovascular diseases and cancer. There are two types of age: chronological age, or the number of years lived by a person or animal, and biological age, which explains a variety of lifestyle factors that may shorten or prolong the life of the person. life, including diet, exercise and environmental exposures. Overall, it has been shown that biological age was a better predictor of all-cause mortality and the onset of illness than chronological age.

For this new study, the researchers looked at rDNA, the most active segment of the genome, which has also been mechanically linked to aging in a number of previous studies. Lemos and lead author, Meng Wang, a researcher at the Department of Environmental Health, have hypothesized that rDNA is a "smoking gun" in the genomic control of aging and could harbor a clock not recognized before. To explore this concept, they examined epigenetic chemical alterations (also referred to as DNA methylation) in CpG sites, where a cytosine nucleotide is followed by a guanine nucleotide. The study focused on rDNA, a small genome segment (13 kilobases) but essential and highly active, as a new marker of age.

Analysis of data sets from mice, dogs, and humans covering the entire genome showed that the researchers' hypothesis was well founded: many CpGs in rDNA showed signs of increased methylation, a consequence of aging. In order to better test the clock, they studied data from 14-week-old mice that responded to caloric restriction, a known intervention that promotes longevity. Mice on a low calorie diet showed significant reductions in rDNA methylation at CpG sites compared to mice whose caloric intake was not limited. In addition, the hypocaloric mice had an age of rDNA younger than their chronological age.

The researchers were surprised to learn that the evaluation of methylation in a small segment of the mammalian genome allowed for clocks as accurate as those built from hundreds of thousands of sites located on the ground. along the genome. They noted that their new approach could prove to be faster and more economical in determining the biological and chronological age than current methods of prospecting for sites scattered throughout the genome. The results highlight the fundamental role of rDNA in aging and highlight its potential as an individual age predictor that can be used on a large scale and can be calibrated for all mammalian species.

It is important to note that clocks respond to interventions, which could allow scientists to study how biological age responds to environmental exposures and lifestyle choices. Being able to determine a specific biological age can give a person an indication of what he is doing better or worse than the general population and could potentially help to control whether a person has high risk of death or illness.

The work of the Lemos Laboratory was partially supported by the National Institute of Environmental Health Sciences, the Lawrence Ellison Medical Foundation and the Richard and Susan Smith Family Foundation, although the authors received no specific funding for these jobs.

"Ribosomal DNA hosts an evolutionarily conserved biological aging clock", Meng Wang, Bernardo Lemos, Genome research, Online February 14, 2019, DOI: 10.1101 / gr.241745.118

photo: iStock

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Chris Sweeney
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Harvard T.H. Chan School of Public Health brings together dedicated experts from many disciplines to train the next generation of world leaders in health and to produce powerful ideas that improve the lives and health of people around the world. As a community of leading scientists, educators and students, we work together to transfer innovative ideas from the laboratory to people's lives – not only through scientific breakthroughs, but also by changing individual behaviors, public policies and health care practices. Each year, more than 400 Harvard Chan School faculty members teach over 1,000 full-time students from around the world and train thousands of others through online courses and training sessions. frames. Founded in 1913 as the head of the Harvard-MIT School of Health Officers, this school is recognized as the oldest public health professional training program in the United States.

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