More physical activity, less TV time may delay Huntington’s age of onset
Minimizing sedentary behavior linked with health benefits in context of disease
Being physically active is significantly associated with a delayed age of the onset of Huntington’s disease and spending more time watching television is significantly linked to an earlier age of onset.
These are the findings of a study that analyzed genetic variants linked with different levels of physical activity and sedentary behaviors, and the possible associations with differences between expected age of onset (based on genetic data) and actual age of onset.
The researchers “recommend increasing physical activity and reducing sedentary behavior to delay the occurrence of motor symptoms” in people who carry a Huntington’s-causing mutation, but haven’t begun to manifest symptoms. The study, “Causal associations of physical activity and leisure sedentary behaviors with age at onset of Huntington’s disease: A mendelian randomization study,” was published in Parkinsonism and Related Disorders.
Huntington’s is caused by excessive repeats of three DNA building blocks, CAG, in the HTT gene, which lead to an abnormally long huntingtin protein being produced that forms clumps that are toxic to nerve cells, resulting in neurodegeneration. The length of the inherited CAG repeats determines the age at which motor symptoms appear, with longer repeat expansions leading to earlier onset.
Being more physically active and minimizing sedentary behavior, such as watching TV, using a computer, and driving a car, have been linked to several health benefits in cardiovascular, metabolic, and even neurodegenerative diseases.
Exercise can help Huntington’s patients maintain their mobility and improve cognitive and daily functioning, while sedentary behavior has been associated “with cognitive decline and structural brain aging,” wrote researchers in China who used a Mendelian randomization to see if physical activity can affect the age of onset in people carrying a Huntington’s-causing mutation. A Mendelian randomization uses genetic information to identify potential cause and effect relationships between an exposure — in this case, physical activity or sedentary behavior — and an outcome, that is, the age at the onset of Huntington’s.
Delaying Huntington’s disease age of onset
The researchers collected data from genome-wide association studies (GWAS), which are designed to detect associations between genetic variants and a certain trait or disease. The studies covered tens of thousands of people of European descent in the U.K. Biobank, a nationwide healthcare study in the U.K.
The team looked specifically at genetic markers linked to four types of physical activity — self-reported moderate-to-vigorous and light activity, as well as overall and vigorous activity measured by a worn sensor — and three sedentary behaviors (watching TV, being on a computer, and driving).
While these variations can’t provide accurate information about the habits of any one person, they can aid in indirectly predicting the behaviors’ effects. For example, if people carrying more variants associated with a sedentary lifestyle have an earlier age at Huntington’s onset, it suggests that reducing sedentary behaviors may delay disease onset.
For this reason, the scientists analyzed relationships between these genetic markers and the residual age at onset in a dataset of more than 9,000 people of European descent with Huntington’s disease. Residual age at onset was defined as the difference between the observed age at the onset of motor symptoms and the expected age at onset based on the number of CAG repeats on the HTT gene. For example, having a residual age at onset of plus 4 represents a four-year delay relative to the expected age at onset.
More genetically determined self-reported light activity or sensor-measured vigorous activity was significantly associated with a later than expected age at Huntington’s onset, results showed. On the other hand, more genetically predicted time spent watching TV was significantly associated with an earlier than expected age at onset. The other types of activities assessed didn’t show statistically significant associations with age at onset.
The data suggest a cause and effect relationship between more physical activity and “reducing the amount of time spent watching TV and delaying the onset of HD [Huntington’s disease],” the scientists wrote. “Therefore, we recommend doing more challenging physical or intellectual activities instead of [sedentary leisure behaviors] to prevent the early [age at onset] of HD.”
The findings may “provide feasible health behavior intervention strategies for delaying the onset of disease in pre-HD populations, helping them improve their quality of life and prolong their health span,” the scientists wrote, noting more research is needed.
About the Author
