Telomere Length, Mitochondrial DNA, and Micronucleus Yield in Response to Oxidative Stress in Peripheral Blood Mononuclear Cells
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Published:2024-01-24
Issue:3
Volume:25
Page:1428
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Borghini Andrea1ORCID, Ndreu Rudina1ORCID, Canale Paola12, Campolo Jonica3ORCID, Marinaro Irene1, Mercuri Antonella1, Turchi Stefano1, Andreassi Maria Grazia1ORCID
Affiliation:
1. CNR Institute of Clinical Physiology, 56124 Pisa, Italy 2. Health Science Interdisciplinary Center, Sant’Anna School of Advanced Studies, 56124 Pisa, Italy 3. CNR Institute of Clinical Physiology, ASST Grande Ospedale Metropolitano Niguarda, 20142 Milan, Italy
Abstract
Telomere shortening, chromosomal damage, and mitochondrial dysfunction are major initiators of cell aging and biomarkers of many diseases. However, the underlying correlations between nuclear and mitochondrial DNA alterations remain unclear. We investigated the relationship between telomere length (TL) and micronucleus (MN) and their association with mitochondrial DNA copy number (mtDNAcn) in peripheral blood mononuclear cells (PBMCs) in response to 100 μM and 200 μM of hydrogen peroxide (H2O2) at 44, 72, and 96 h. Significant TL shortening was observed after both doses of H2O2 and at all times (all p < 0.05). A concomitant increase in MN was found at 72 h (p < 0.01) and persisted at 96 h (p < 0.01). An increase in mtDNAcn (p = 0.04) at 200 µM of H2O2 was also found. In PBMCs treated with 200 µM H2O2, a significant inverse correlation was found between TL and MN (r = −0.76, p = 0.03), and mtDNA content was directly correlated with TL (r = 0.6, p = 0.04) and inversely related to MN (r = −0.78, p = 0.02). Telomere shortening is the main triggering mechanism of chromosomal damage in stimulated T lymphocytes under oxidative stress. The significant correlations between nuclear DNA damage and mtDNAcn support the notion of a telomere–mitochondria axis that might influence age-associated pathologies and be a target for the development of relevant anti-aging drugs.
Funder
Department of Biomedical Sciences, National Research Council
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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