Scientists have known for years that age is a leading risk factor for the development of many types of cancer, but why aging increases cancer risk remains unclear.
Researchers suspect that DNA methylation, or the binding of chemical tags, called methyl groups, onto DNA, may be involved. Methyl groups activate or silence genes, by affecting interactions between DNA and the cell’s protein-making machinery.
Zongli Xu, Ph.D., and Jack Taylor, M.D., Ph.D., researchers from the National Institute of Environmental Health Sciences (NIEHS), part of NIH, identified DNA methylation sites across the human genome that changed with age. They demonstrated that a subset of those sites — the ones that become increasingly methylated with advancing age — are also disproportionately methylated in a variety of human cancers. Their findings were published online in the journal Carcinogenesis.
“You can think of methylation as dust settling on an unused switch, which then prevents the cell from turning on certain genes,” Taylor said. “If a cell can no longer turn on critical developmental programs, it might be easier for it to become a cancer cell.”
Xu and Taylor made the discovery using blood samples from participants in the Sister Study, a nationwide research effort to find the environmental and genetic causes of breast cancer and other diseases. More than 50,000 sisters of women who have had breast cancer are participating in the study.
The researchers analyzed blood samples from 1,000 women, using a microarray that contained 27,000 specific methylation sites. Nearly one-third of the sites showed increased DNA methylation in association with age. They then looked at three additional data sets from smaller studies that used the same microarray and found 749 methylation sites that behaved consistently across all four data sets. As an additional check, they consulted methylation data from normal tissues and seven different types of cancerous tumors in The Cancer Genome Atlas, a database funded by the National Cancer Institute and the National Human Genome Research Institute.
Taylor said that DNA methylation appears to be part of the normal aging process and occurs in genes involved in cell development. Cancer cells often have altered DNA methylation, but the researchers were surprised to find that 70-90 percent of the sites associated with age showed significantly increased methylation in all seven cancer types. Taylor suggests that age-related methylation may disable the expression of certain genes, making it easier for cells to transition to cancer.
The research also determined how fast these methylation events accumulate in cells. They occur at a rate of one per year, according to Xu.
“On your 50th birthday, you would have 50 of these sites [from the subset of 749] that have acquired methyl groups in each cell,” Xu said. “The longer you live, the more methylation you will have.”
For future work, Xu and Taylor want to examine more samples, using a newer microarray that will explore methylation at 450,000 genomic methylation sites. The additional samples and larger microarray, which will provide 16 times more genomic coverage, will allow them to address whether environmental exposures during adulthood or infancy affect methylation profiles. These additional studies will help scientists better understand why methylation happens as people march toward their retirement years.
DNA methylation is one of several epigenetic mechanisms that can control gene expression without changes in DNA sequence. This study is part of a broader research effort, funded by NIEHS, to understand how environmental and other factors affect epigenetic mechanisms in relation to health.
NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit http://www.niehs.nih.gov. Subscribe to one or more of the NIEHS news lists (http://www.niehs.nih.gov/news/newslist/index.cfm) to stay current on NIEHS news, press releases, grant opportunities, training, events, and publications.About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.
NIH...Turning Discovery Into Health ®
Reference: Xu Z, Taylor JA. 2014. Genome-wide age-related DNA methylation changes in blood and other tissues relate to histone modification, expression, and cancer. Carcinogenesis 35(2):356-364.Grant numbers:
Robin Arnette | Newswise
Further reports about: > Cancer > DNA > DNA methylation > Environmental Health > Environmental Health Sciences > Human vaccine > Management Insights feature > NIEHS > NIH > blood sample > breast cancer > cancerous tumor > epigenetic mechanism > genetic mechanism > health services > human cancer > medical research > methyl group > types of cancer
Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland
Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy