DNA status in brain and heart as prominent co-determinant for life span? Assessing the different degrees of DNA damage, damage susceptibility, and repair capability in different organs of young and old mice

• Published in: Mechanisms of ageing and development 1996-08, Vol.89 (2), p.79-94
• Main Authors: Zahn, Rudolf K., Jaud, Susanne, Schröder, Heinz-Christof, Zahn-Daimler, Gertrud
• Format: Article
• Language: English
• Subjects: Aging - genetics; Alkali-labile sites; Alkalies; Animals; Biological and medical sciences; Brain - metabolism; Chemical Fractionation; Co-determinant for life span; Cross-links; Damage susceptibility; Development. Metamorphosis. Moult. Ageing; DNA Damage; DNA Repair; DNA strand break; Evaluation Studies as Topic; Female; Filtration - methods; Fundamental and applied biological sciences. Psychology; HeLa Cells; Humans; Longevity - physiology; Mice; Mice, Inbred Strains; Myocardium - metabolism; Organ Specificity - physiology; Repair; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/0047-6374(96)01738-1

Alkaline filter elution has been modified by a freeze-grinding step that allows the evaluation of the DNA status of whole tissue, including mouse tail cross-sections, with only small additional artefacts. Four to seven different organs from individually coordinated female NMRI mice, rated as young when 2–3 months, and as old when 24–27 months, of age, have been used. Tissues of individual mice differ significantly in their DNA status. Alkali-labile sites are relatively rare and differ in amount in the different organs in the young. They show significant increases in the old, reaching the highest values in the brain and the heart. Proteinase K dependant DNA-protein cross-links are not prominent nor are they increased with age in some organs, except in the brain and the heart. DNA damage susceptibility was measured after application of 3.5 μM nitoquinolin-N-oxide to 15 mg fresh tissue pieces for 90 min. The susceptibilty is large and varying in wide ranges in the different organs. Upon 3 h post-exposure incubation in full medium all samples showed DNA repair, the young reach nearly complete repair in the lung, while repair, generally, in the old is significantly decreased. In old brain and heart it is even near zero. This together with high values in alkali-labile sites and protein-DNA cross-linking suggests that these two organs may act as pacemakers and play a role as prominent co-determinants for the life span of the species.