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Research Paper|Volume 12, Issue 3|pp 2070—2083

Mitochondria and aging in older individuals: an analysis of DNA methylation age metrics, leukocyte telomere length, and mitochondrial DNA copy number in the VA normative aging study

Jacopo Dolcini1,2, Haotian Wu1, Jamaji C. Nwanaji-Enwerem3, Marianthi-Anna Kiomourtozlogu1, Akin Cayir3,4, Marco Sanchez-Guerra5, Pantel Vokonas6, Joel Schwarz3, Andrea A. Baccarelli1
  • 1Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA
  • 2Department of Biomedical Sciences and Public Health, Section of Hygiene and Preventive Medicine, Medical School, Polytechnic University of Marche, Ancona, Italy
  • 3Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
  • 4Vocational Health College, Canakkale Onsekiz Mart University, Canakkale, Turkey
  • 5Department of Developmental Neurobiology, National Institute of Perinatology, Lomas Virreyes, Mexico
  • 6Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
Received: October 7, 2019Accepted: January 2, 2020Published: February 2, 2020
https://doi.org/10.18632/aging.102722

Copyright: © 2020 Dolcini 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

Population aging is a looming global health challenge. New biological aging metrics based on DNA methylation levels have been developed in addition to traditional aging biomarkers. The prospective relationships of aging biomarkers with mitochondrial changes are still not well understood. Here, we examined the prospective associations of mitochondrial copy number (mtDNAcn) with several aging biomarkers – DNAm-Age, DNAm-PhenoAge, DNAm-GrimAge, and leukocyte telomere length. We analyzed 812 individuals from Veteran Affairs Normative Aging Study (NAS) with available blood samples from 1999-2013. Whole blood mtDNAcn and relative leukocyte telomere length were measured via qPCR. DNA methylation was assessed and used to calculate DNAm-Age, DNAm-GrimAge, and DNAm-PhenoAge. Linear mixed models were used to quantify the associations of mtDNAcn with DNAm-Age, DNAm-GrimAge, DNAm-PhenoAge, and leukocyte telomere length. In multivariable cross-sectional analyses, mtDNAcn is negatively associated with DNAm-Age PhenoAge and DNAm-PhenoAge. In contrast, mtDNAcn is associated with prospective measures of higher DNAm-PhenoAge and shorter leukocyte telomere length. Our study shows that higher mtDNAcn is associated with prospective measures of greater DNAm-PhenoAge and shorter leukocyte telomere length independent of chronological age. This indicates a role for mitochondrial in aging-related disease and mortality, but not the departure of biological age from chronological age.