DNA Methylation Age is Elevated in Breast Tissue of Healthy Women
Epigenetics is the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself. It has been shown that epigenetic biomarkers, such as DNA methylation—a process by which methyl groups are added to the DNA molecule—can increase cancer risk through altering gene expression. UCLA professor Steve Horvath, Ph.D., developed a DNA methylation based age estimation method known as the epigenetic clock. In 2013, Dr. Horvath further developed his discovery into the Horvath clock, an age estimation method based on 353 epigenetic markers on the DNA.
The most startling features of the Horvath clock are its high accuracy, and its applicability to a broad spectrum of tissues and cell types. Since it allows one to contrast the ages of different tissues from the same subject, it can be used to identify tissues that show evidence of accelerated age due to disease.
In a presentation at the upcoming 25th Clinical Applications for Age Management Medicine Conference in Tucson, AZ, Dr. Mary Sehl, a colleague of Dr. Horvath at UCLA, will present the results of a study on which she was the lead author, that takes this area of research a step further. It suggests that breast tissue ages faster than the rest of the body, which may explain its susceptiblity to cancer. Thus, while one assumption was that some tissue ages more quickly as a result of disease, Dr. Sehl suggests that the opposite may be true in the case of breast tissue.
"Our laboratory is interested in accelerated epigenetic aging in breast tissue and the potential role of hormonal factors in driving this acceleration," said Dr. Sehl. While limited evidence suggests female breast tissue ages faster than other parts of the body, those results were obtained using pooled data mostly based on adjacent tissues from breast cancer patients. "If you look across tissues, the breast actually looks older than the rest of the body," said Dr. Sehl. "We wanted to validate whether or not the breast was actually older than the rest of the body."
In order to accomplish that, they obtained tissue donated from women who did not have a history of breast cancer. The also obtained matched blood samples from the same individuals. As stated in their study that was published in Breast Cancer Research [Breast Cancer Res Treat (2017) 164:209–219], the goal was to validate their initial finding of advanced DNA methylation age in breast tissue, by directly comparing it to that of peripheral blood tissue from the same individuals, and to do a preliminary assessment of hormonal factors that could explain the difference.
"To our knowledge," said Dr. Sehl, "this is the first study to demonstrate that breast tissue epigenetic age exceeds that of blood tissue in healthy female donors." The acceleration, noted Dr. Sehl, is especially true at earlier ages. "It is in the ages between puberty and adulthood that this acceleration takes place," she said. "We think that this is possibly due to accumulated estrogen stimulation and monthly self-cycling that exposes the breast tissue to these factors," said Dr. Sehl. "But we're doing additional research to see if some of the same factors that promote breast cancer—for example, early menarche, and later menopause accumulated estrogen exposure—is related to this acceleration in the breast tissue."
"The significance," continued Dr. Sehl, "is if we can show that DNA methylation age or epiginetic age is older in the breast, it raises the question of whether this is a mechanism by which people are at increased risk of breath cancer." The hypothesis, in other words, is that one of the reasons why breast cancer is so common, relative to other types of cancer, is that the breast is aging faster, and this is true even in healthy women.
Dr. Sehl will delve much further into the research that she and Dr. Horvath and their assocaites are conducting, and its implications, when she speaks at the AMMG conference in November
For the latest information on the upcoming Age Management Medicine conference, visit www.agemed.org.
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