title: Increased epigenetic age and granulocyte counts in the blood of Parkinson's disease patients.
abstract: It has been a long standing hypothesis that blood tissue of PD Parkinson's disease (PD) patients may exhibit signs of accelerated aging. Here we use DNA methylation based biomarkers of aging ("epigenetic clock") to assess the aging rate of blood in two ethnically distinct case-control data sets. Using n=508 Caucasian and n=84 Hispanic blood samples, we assess a) the intrinsic epigenetic age acceleration of blood (IEAA), which is independent of blood cell counts, and b) the extrinsic epigenetic age acceleration rate of blood (EEAA) which is associated with age dependent changes in blood cell counts. Blood of PD subjects exhibits increased age acceleration according to both IEAA (p=0.019) and EEAA (p=6.1 x 10(-3)). We find striking differences in imputed blood cell counts between PD cases and controls. Compared to control subjects, PD subjects contains more granulocytes (p=1.0 x 10(-9) in Caucasians, p=0.00066 in Hispanics) but fewer T helper cells (p=1.4 x 10(-6) in Caucasians, p=0.0024 in Hispanics) and fewer B cells (p=1.6 x 10(-5) in Caucasians, p=4.5 x 10(-5) in Hispanics). Overall, this study shows that the epigenetic age of the immune system is significantly increased in PD patients and that granulocytes play a significant role.
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.|Department of Biostatistics, UCLA Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.affiliation: Department of Neurology, UCLA School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.|Department of Epidemiology, UCLA Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA.|Department of Environmental Health, UCLA Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Beate R
authors.initials: BR
authors.lastname: Ritz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D019175:DNA Methylation / Q000502:physiology; D044127:Epigenesis, Genetic; D005260:Female; D006098:Granulocytes / Q000502:physiology*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D012307:Risk Factors
chemical_list: D007980:Levodopa
keywords: DNA methylation; Parkinson's disease; epigenetic clock; epigenetics; granulocyte; neutrophil