Variant Linked to Higher Dopamine Levels May Improve Mobility in Frail Adults

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Senior man walking by the riverside
[Source: Westend61/Getty Images]

A genetic variant linked to higher dopamine levels appears to have a positive impact on mobility in frail older adults, according to University of Pittsburgh research.

Catechol-O-methyltransferase is an enzyme encoded by the COMT gene that inactivates dopamine, epinephrine and norepinephrine. A specific mutation in this gene – the Val(158)Met polymorphism – is known to impact levels of dopamine that are released into the body.

Lower levels of dopamine have been linked to worse mobility in frail older adults. Caterina Rosano, a researcher at the Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, and colleagues therefore decided to investigate if the Val(158)Met COMT variant was linked to mobility in this group.

“Most people think about dopamine’s role in mobility in the context of Parkinson’s disease, but not in normal aging,” said Rosano. “We were curious to see if a genetic predisposition to produce more or less dopamine was related to mobility in individuals who had some level of frailty, yet did not have dementia, parkinsonism or any other neurological condition.”

Individuals with a Met/Met genotype have the highest levels of dopamine, followed by Met/Val heterozygotes and then Val/Val homozygotes. As reported in the Journal of the American Geriatrics Society, Rosano and team genotyped a group of 3744 adults aged 65 years or older that had no evidence of Parkinson’s disease for this variant. Of this group, 685 were Black and 3059 were White and 1911 were considered to be frail, defined as a “decreased resistance to stressors and increased vulnerability to adverse outcomes.”

The team found that the impact of the variant was statistically significant in frail individuals but not in those that did not fit the definition of frailty and in this group Met/Met homozygotes walked around 13% faster (0.10 m/s difference between groups) than Val/Val homozygotes.

Notably, when the researchers stratified the group by ethnicity, the association was significant in White but not Black individuals. However, there was a similar difference in gait speed in both groups, so the lack of significance in Black participants may have been influenced by low sample size.

The researchers acknowledge that there are likely to be several genes involved in regulation of frailty, mobility and walking speed, and that their results need to be replicated, but believe their findings add weight to the evidence suggesting that dopamine levels can have a strong impact on mobility in later life.

“There are a lot of individuals living in the community who have dopamine levels toward the lower end of normal who don’t have Parkinson’s disease or psychiatric conditions,” said Rosano. “If we give dopamine to these people, could we make them more resilient? That’s what we don’t know yet.”

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