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Research Paper|Volume 7, Issue 5|pp 294—306

The cerebellum ages slowly according to the epigenetic clock

Steve Horvath1,2, Vei Mah3, Ake T. Lu1, Jennifer S. Woo3, Oi-Wa Choi4, Anna J. Jasinska4, José A. Riancho5, Spencer Tung3, Natalie S. Coles6, Jonathan Braun3, Harry V. Vinters3, L. Stephen Coles6
  • 1Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
  • 2Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA
  • 3Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA
  • 4Center for Neurobehavioral Genetics, University of California, Los Angeles, CA 90095, USA
  • 5Department of Internal Medicine, H.U. Marqués de Valdecilla-IFIMAV-University of Cantabria, Santander 39008, Spain
  • 6UCLA Molecular Biology Institute; Department of Chemistry and Biochemistry; Los Angeles, CA 90095, USA
* Passed away during the study
Received: April 3, 2014Accepted: May 5, 2015Published: May 11, 2015
https://doi.org/10.18632/aging.100742

Copyright: © 2015 Horvath et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Studies that elucidate why some human tissues age faster than others may shed light on how we age, and ultimately suggest what interventions may be possible. Here we utilize a recent biomarker of aging (referred to as epigenetic clock) to assess the epigenetic ages of up to 30 anatomic sites from supercentenarians (subjects who reached an age of 110 or older) and younger subjects. Using three novel and three published human DNA methylation data sets, we demonstrate that the cerebellum ages more slowly than other parts of the human body. We used both transcriptional data and genetic data to elucidate molecular mechanisms which may explain this finding. The two largest superfamilies of helicases (SF1 and SF2) are significantly over-represented (p=9.2×10−9) among gene transcripts that are over-expressed in the cerebellum compared to other brain regions from the same subject. Furthermore, SNPs that are associated with epigenetic age acceleration in the cerebellum tend to be located near genes from helicase superfamilies SF1 and SF2 (enrichment p=5.8×10−3). Our genetic and transcriptional studies of epigenetic age acceleration support the hypothesis that the slow aging rate of the cerebellum is due to processes that involve RNA helicases.