Research Paper|Volume 11, Issue 4|pp 1240—1251

Epigenetic signature: implications for mitochondrial quality control in human aging

Patrizia D’Aquila¹, Alberto Montesanto¹, Francesco De Rango¹, Francesco Guarasci¹, Giuseppe Passarino¹, Dina Bellizzi¹

¹Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende 87036, Italy

* * Equal contribution

Received: January 11, 2019Accepted: February 12, 2019Published: February 20, 2019

Copyright: © 2019 D’Aquila et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Maintenance of functional mitochondria is essential to prevent damage leading to aging and diseases. What is more, the research of biomarkers of aging is focusing on better predicting functional capability along the lifetime beyond chronological age. Aim of this study was to identify novel CpG sites the methylation of which might be correlated to the chronological and biological age. We performed methylation analyses of the CpG sites in candidate genes involved in mitochondrial biogenesis, mitophagy, fusion, and fission, all key quality control mechanisms to ensure maintenance of healthy mitochondria and homeostasis during aging, using DNA samples from two independent datasets composed by 381 and 468 differently-aged individuals, respectively. Twelve potential CpG predictors resulted associated with aging in the discovery dataset. Of these, two sites located within RAB32 and RHOT2 genes were replicated in the second dataset. What is more, individuals exhibiting methylation levels of the RAB32 CpG site higher than 10% were observed more prone to disability than people with lower levels.

These results seem to provide the first evidence that epigenetic modifications of genes involved in mitochondrial quality control occur over time according to the aging decline, and may then represent potential biomarkers of both chronological and biological age.