What causes aging? A new study that links two known aspects of aging — genetic mutations and epigenetic changes — may help find the answer. (Image credit: hh5800 via Getty Images)
Scientists often use an “epigenetic clock” to estimate biological age, but the mechanisms that drive it are not fully understood. Now, researchers have discovered a clue: the clock is synchronized with random mutations that accumulate in DNA as we age.
It is known that during a person’s life, mutations accumulate in cellular DNA. This occurs as a result of cell replication or exposure to external factors such as radiation and infections. In addition, with age, the mechanisms responsible for repairing DNA damage begin to function less effectively. With increasing age and accumulation of mutations, the risk of developing immune diseases, neurodegeneration and cancer increases.
However, mutations in DNA do not tell the whole story of the aging process.
There are also molecular changes that occur “on top” of the DNA. These changes, known as “epigenetic,” do not directly affect the underlying DNA code. They involve turning genes on or off, or changing their activity. Research shows that the pattern of epigenetic marks on DNA changes predictably with age, and the epigenetic clock tracks these changes to estimate the “biological age” of a particular person or tissue.
A new study published January 13 in the journal Nature Aging takes a fresh look at the relationship between these genetic and epigenetic changes.
“This is a significant study,” said Jesse Poganic, a researcher at Brigham and Women's Hospital and an instructor of medicine at Harvard Medical School who was not involved in the study.
“People are rightly critical of the so-called black box of the epigenetic clock,” he added to Live Science. There are many questions about what exactly causes the epigenetic changes we see, and whether they actually cause aging or simply reflect it — like wrinkles, which are a sign of aging skin but not the cause of it.
“Any further understanding of the underlying mechanisms involved in this process will ultimately help us move the field forward,” Poganic said.
Cascade of changes
The study began with an idea from co-author Stephen Cummings, Ph.D., executive director of the San Francisco Coordinating Center at the University of California, San Francisco, who suggested that gene mutations might be directly linked to changes recorded by the epigenetic clock. And ultimately, “that’s what we found,” said Cummings, who is also a senior research scientist at the Sutter Health California Pacific Medical Center Research Institute.
“These two events turned out to be very closely related,” he told Live Science.
To explain the logic of my theory, let's delve a little into chemistry.
One common mechanism of epigenetics, which most epigenetic clocks rely on, is called DNA methylation. This process involves molecules known as methyl groups that attach to cytosine (C), one of the four “letters” in DNA. Methylation occurs at sites in DNA molecules where the C is next to a guanine (G), which are known as CpG sites. However, if a mutation occurs and either the C or G changes, that site is no longer a CpG and is therefore much less likely to be methylated.
“So the mutation could lead to a loss of methylation,” explained senior study co-author Trey Ideker, a professor at the UC San Diego School of Medicine and the Jacobs School of Engineering.
“And it turns out that it might actually be the other way around,” Ideker added. Methylation, in turn, can influence where DNA mutations occur. If a methyl group attaches to a certain part of C, it can cause a chemical reaction that destabilizes the C, making it more susceptible to mutation.
Sourse: www.livescience.com
