Abstract
Epigenetic regulation may contribute to the beneficial effects of physical activity against age-related neurodegeneration. For example, epigenetic alterations of the gene encoding for α-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 on SNCA epigenetic 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, oligomeric α-synuclein and DNA methyltransferase concentrations in the blood). Here, the SNCAI1 methylation status increased with ageing, and consistent with this result, low α-synuclein levels were found in the blood. The direct relationship between SNCAI1 methylation and α-synuclein levels was observed in samples characterized by blood α-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 oligomeric α-synuclein levels. Taken together, our data shed light on ageing- and physical exercise-induced changes on the SNCA methylation status and protein levels of α-synuclein.
Highlights
Ageing is characterized by common cellular features, such as increased oxidative stress, reduction in protein synthesis, mitochondrial dysfunction, stem cell depletion, and telomere attrition [1]
The present study explored whether, in healthy individuals, physical activity or age is related to different parameters evaluated at the peripheral level, including the CpG site methylation within SNCA intron 1 (SNCAI1); the concentration of the protein encoded by SNCA (α-syn), considering total levels and the contribution of its oligomeric form; and the levels of the DNA methyltransferase enzymes of maintenance (Dnmt1) and ex novo (Dnmt3a)
The calculation of mean values and correlation analyses of the parameters related to SNCA epigenetic modification were initially performed in the entire population
Summary
Ageing is characterized by common cellular features, such as increased oxidative stress, reduction in protein synthesis, mitochondrial dysfunction, stem cell depletion, and telomere attrition [1]. Regular exercise has been suggested to affect the methylation status of global and CpG-rich specific genes in the muscle cells, the different peripheral tissues, and the brain. The gene for neurotrophic factor BDNF (brain-derived growth factor) is known to be remodelled epigenetically in the hippocampus in response to physical exercise [13]. Such studies are consistent with the hypothesis that epigenetics is central to coordinating the transcriptional response to the environment, as well as being involved in neuronal development, maintenance, and degeneration processes [14,15,16]. It is not surprising that physical exercise has been
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