Study identifies previously unknown molecular pathway in aging.
It is known that the age-related growth differentiation factor 11 (GDF11) is member of the transforming growth factor β superfamily of proteins. Circulating GDF11 concentrations appear to decline with age, and its depletion is associated with cardiac hypertrophy and other morbidities.
Knowledge of GDF11 regulation is limited, however, and the effects of natural genetic variation on GDF11 levels are currently undefined. Now, a study from researchers at the University of Georgia has shown that GDF11 is under genetic control, introducing a new pathway by which genetics regulates aging and disease. The team state that since growth differentiation factor 11 (GDF11) levels are under genetic control, the global medical community can now identify the genes responsible for GDF11 levels and its changes with age.
Previous studies have found that blood levels of this hormone, growth differentiation factor 11, decrease over time with most of the depletion occurring by middle age. Restoration of GDF11 has been shown to reverse 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. The current study shows that levels of this hormone are determined by genetics, representing another potential mechanism by which aging is encoded in the genome.
The current study investigated the relationship between GDF11 levels and markers of aging such as lifespan in 22 genetically diverse inbred mice strains. Results show that the strains with the highest GDF11 levels tended to live the longest.
The lab used gene mapping to identify seven candidate genes that determine blood GDF11 concentrations at middle age, demonstrating for the first time that GDF11 levels are highly heritable. Results show interactions between age and genetic background determined GDF11 concentrations, which were unaffected by sex. Data findings show high heritability of GDF11 levels and that GDF11 may also serve as a novel predictor of mammalian life span. The group conclude that, essentially, they have found a missing piece of the aging/genetics puzzle.
The team surmise that they have made an important step toward learning about aging and the pathways that drive it. For the future, the researchers state that they now plan to investigate why GDF11 levels decrease later in life and whether they can be sustained to prevent disease.
Source: University of Georgia