Epigenetic Modifications of theα-Synuclein Gene and Relative Protein Content Are Affected by Ageing and Physical Exercise in Blood from Healthy Subjects

Abstract

Epigenetic regulation may contribute to the beneficial effects of physical activity against age-related neurodegeneration. For example, epigenetic alterations of the gene encoding forα-synuclein (SNCA) have been widely explored in both brain and peripheral tissues of Parkinson’s disease samples. However, no data are currently available about the effects of physical exercise onSNCAepigenetic regulation in ageing healthy subjects. The present paper explored whether, in healthy individuals, age and physical activity are related to blood intron1-SNCA(SNCAI1) methylation, as well as further parameters linked to such epigenetic modification (total, oligomericα-synuclein and DNA methyltransferase concentrations in the blood). Here, theSNCAI1methylation status increased with ageing, and consistent with this result, lowα-synuclein levels were found in the blood. The direct relationship betweenSNCAI1methylation andα-synuclein levels was observed in samples characterized by bloodα-synuclein concentrations of 76.3 ng/mg protein or lower (confidence interval (CI) = 95%). In this selected population, higher physical activity reduced the total and oligomericα-synuclein levels. Taken together, our data shed light on ageing- and physical exercise-induced changes on theSNCAmethylation status and protein levels ofα-synuclein.