Maria Fasolino1, Shuo Liu2, Yinsheng Wang2,3, Zhaolan Zhou1. 1. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. 2. Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521, USA. 3. Department of Chemistry, University of California, Riverside, CA 92521, USA.
Abstract
AIM: We aimed to couple brain region-specific changes in global DNA methylation over aging to underlying cellular and molecular environments. MATERIALS & METHODS: We measured two major forms of DNA methylation and analyzed Dnmt, Tet and metabolite levels in the striatum and substantia nigra (SN) over aging in healthy male mice. RESULTS: The ratio of 5-hydroxymethylcytosine to 5-methylcytosine increases over aging in the SN, and 5-hydroxymethylcytosine increases preferentially in dopaminergic neurons. Additionally, this age-dependent alteration in methylation correlates with a reduction in the ratio of α-ketoglutarate to succinate in the SN. CONCLUSION: Distinct cellular and molecular environments correlate with aging-associated methylation changes in the SN, implicating this epigenetic mechanism in the susceptibility of this brain region to age-related cell loss.
AIM: We aimed to couple brain region-specific changes in global DNA methylation over aging to underlying cellular and molecular environments. MATERIALS & METHODS: We measured two major forms of DNA methylation and analyzed Dnmt, Tet and metabolite levels in the striatum and substantia nigra (SN) over aging in healthy male mice. RESULTS: The ratio of 5-hydroxymethylcytosine to 5-methylcytosine increases over aging in the SN, and 5-hydroxymethylcytosine increases preferentially in dopaminergic neurons. Additionally, this age-dependent alteration in methylation correlates with a reduction in the ratio of α-ketoglutarate to succinate in the SN. CONCLUSION: Distinct cellular and molecular environments correlate with aging-associated methylation changes in the SN, implicating this epigenetic mechanism in the susceptibility of this brain region to age-related cell loss.
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