Rob Pazdro, left, and Yang Zhou led a study looking at a new pathway by which genetics regulates aging and disease. Credit: Cal Powell/University of Georgia
Uni of Georgia scientists have shown a hormone instrumental in the aging process is under genetic control, introducing a new pathway by which genetics regulates aging and disease. Previous studies have found that blood levels of this hormone, growth differentiation factor 11, decrease over time. Restoration of GDF11 reverses cardiovascular aging in old mice and leads to muscle and brain rejuvenation, a discovery that was listed as one of the top 10 breakthroughs in science in 2014.
Scientists in the UGA College of Family and Consumer Sciences have now discovered that levels of this hormone are determined by genetics, representing another potential mechanism by which aging is encoded in the genome. Future studies will seek to reveal why GDF11 levels decrease later in life and whether they can be sustained to prevent disease. “Since it is under genetic control, we can find the genes responsible for GDF11 levels and its changes with age,” said Assistant Prof. Pazdro.
The study confirmed results from previous experiments showing GDF11 levels decrease over time and most of the depletion occurs by middle age. In addition, the study examined the relationship between GDF11 levels and markers of aging such as lifespan in 22 genetically diverse inbred mice strains. Of note, the strains with the highest GDF11 levels tended to live the longest. Using gene mapping, Pazdro’s team then identified 7 candidate genes that may determine blood GDF11 concentrations at middle age, demonstrating for the first time that GDF11 levels are highly heritable and unaffected by sex. It was estimated that 74.52% of phenotypic variation in GDF11 levels of the mice was attributable to genetic background. They used the Mouse Phenome Database to screen for phenotypes that correlate with GDF11. Interestingly, GDF11 levels predicted median strain life spans.
“Essentially, we found a missing piece of the aging/genetics puzzle,” Pazdro said. “Very generally, we’ve made an important step toward learning about aging and why we age and what are the pathways that drive it. It’s the first step down a long road, but it’s an important step.”
http://medicalpartnership.usg.edu/?/news/article/uga-researchers-make-link-between-genetics-aging
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