By Brie Zeltner, The Plain Dealer
August 21, 2013
CLEVELAND, Ohio– A mother's genes may accelerate how rapidly her children age, according to a new study from an international team of researchers published today in Nature.
The research team, which included Case Western Reserve University and University Hospitals Case Medical Center adjunct professor of neurology Dr. Barry Hoffer, found that mice who inherit mutations in a particular type of DNA from their mothers experience accelerated aging compared to those who don't.
“This answers a longtime question we've had,” said Hoffer, “about the role of the mother's DNA in the aging process.” Until 2010, Hoffer also served as the director of the Intramural Research Center at the National Institute on Drug Abuse, part of the National Institutes of Health. He remains a principal investigator with the NIH.
There are two types of DNA in the body, Hoffer said. The first, which most of us learned about in biology class, sits in each cell's central processing center: the nucleus. The second is in the mitochondria, the tiny self-contained structures known as the cell's energy-producers. Mitochondria, thousands in most cells, take in nutrients, break them down, and spit out the energy needed to power every process in the body.
Unlike the DNA in the nucleus, which is derived equally from each parent, mitochondrial DNA comes exclusively from the mother. Because many of the mitochondria's 37 genes provide instructions for making proteins that are directly involved in the production of energy for the cell, any problems in these genes can have serious consequences for an animal.
To guard against such problems, the mitochondria uses a “proofreading” enzyme called PolgA as a quality-control measure: as the genetic code of the DNA within the mitochondria is read and transcribed to produce proteins, PolgA throws out mistakes. Members of the current research group from the Karolinska Institutet in Sweden found in 2004 that eliminating this protective enzyme rapidly increases the aging process in mice.
“So we have this repair mechanism, and when the number of our mutations exceed our ability to repair, that's when cells die and we age,” Hoffer said.
Mice with defective PolgA in those experiments very quickly showed many of the symptoms we associate with aging: congestive heart failure, kidney failure, osteoporosis, changes in brain biochemistry, even a “dowager's hump.”
In the new study, the research group manipulated the genes of mice to have mutations in their maternally-inherited mitochondrial DNA (mtDNA). Doing so accelerated the rate of aging in the mice even when they had a normally functioning PolgA enzyme. When the mutated mtDNA mice were also missing the PolgA enzyme, the effect was even more striking.
“There's proof, for the first time, that something you've inherited from your mother can add to your pre-existing tendency for aging,” Hoffer said. “Inherited mitochondrial DNA can play an important role on its own and can also add to accelerated aging.”
Hoffer said the mice “will become a platform to study ways to mitigate the pace of aging,” and he plans to continue work on finding ways to manipulate these maternally-transmitted mutations.
“I'll be looking at various ways, either through diet or drugs, of slowing or reversing this process,” he said.
While there have been two recent studies showing that it may be possible to remove defective mtDNA and replace it with normal DNA, Hoffer said right now the idea is “very speculative and probably decades away.”
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12474.html
http://www.cleveland.com/healthfit/index.ssf/2013/08/mothers_genes_may_accelerate_a.html
