Genomic instability in a healthy elderly population: a pilot study of possible cytogenetic markers related to ageing

• Published in: Mutagenesis Vol. 25; no. 5; pp. 455 - 462
• Main Authors: Mladinic, Marin, Kopjar, Nevenka, Milic, Mirta, Buljevic Dasovic, Andrea, Huzak, Miljenko, Zeljezic, Davor
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.09.2010
• Subjects: Aged; Aging - drug effects; Aging - genetics; Biological and medical sciences; Case-Control Studies; Chromosomes, Human - genetics; Comet Assay; Cytogenetic Analysis - methods; Demography; Diverse techniques; DNA Glycosylases - metabolism; Female; Fundamental and applied biological sciences. Psychology; Genetic Markers; Genomic Instability - drug effects; Genomic Instability - genetics; Health; Humans; Hydrogen Peroxide - pharmacology; In Situ Hybridization, Fluorescence; Life Style; Lymphocytes - drug effects; Lymphocytes - metabolism; Male; Metaphase - drug effects; Metaphase - genetics; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; Pilot Projects; Regression Analysis; Translocation, Genetic - drug effects; Human; Pilot; Mutagenesis; Genomics; Ageing; Cytogenetics; Instability; Population; Elderly
• ISSN: 0267-8357; 1464-3804; 1464-3804
• DOI: 10.1093/mutage/geq027

Accumulation of DNA damage may play a significant role in the aetiology of the ageing process. Although genomic lesions increase the risk of cancer, many elderly individuals do not suffer from neoplasia in spite of their late age. We aimed to evaluate the rate of genome integrity impairment among elderly subjects without recorded chronic or inflammatory diseases and malignancies. Thirty-one generally healthy elderly subjects (age 69.3 ± 3.7 years) were studied. Subjects matched control subjects by gender and lifestyle factors. Frequencies of structural chromosome aberrations and translocations applying fluorescence in situ hybridization chromosome painting probes, levels of primary DNA damage and oxidative lesions cleaved by hOGG1 enzyme using alkaline and hOGG1-modified comet assay were recorded in peripheral blood leukocytes. Also, susceptibility of the genome to H2O2-induced damage as a marker of antioxidative status was evaluated. Translocation yields and rates of chromatid breaks and acentric fragments were significantly higher among elderly subjects. Furthermore, a significant increase in the level of primary genome lesions and hOGG1-sensitive sites in DNA was detected, while the results of the comet assay following H2O2 pre-treatment suggested decreased levels of antioxidant protection in leukocytes. The results obtained may indicate that accumulation of genome damage observed in leukocytes of elderly subjects as surrogate cells is intertwined with the ageing process. Taking this into consideration with the medical records of the study subjects, the results support other authors’ findings that the accumulation of basal genome damage might not inevitably trigger the mechanism that enforces induced development of neoplasia.