Effects of aging and caloric restriction on I-compounds in liver, kidney and white blood cell DNA of male Brown-Norway rats

• Published in: Mechanisms of ageing and development Vol. 58; no. 2; pp. 279 - 296
• Main Authors: Randerath, Erika, Hart, Ronald W., Turturro, Angelo, Danna, Tracy F., Reddy, Ranjani, Randerath, Kurt
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.05.1991; Elsevier Science
• Subjects: Aging - metabolism; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Diet; DNA - blood; DNA - metabolism; Dna, deoxyribonucleoproteins; Energy Intake; Fundamental and applied biological sciences. Psychology; Kidney - metabolism; Kinetics; Leukocytes - metabolism; Liver - metabolism; Male; Neoplasms, Experimental - etiology; Nucleic acids; Rats; Rats, Inbred BN; Tissue Distribution; Vertebrata; Blood cell; Mammalia; Deficient diet; Rat; DNA; Liver; Rodentia; Structure modification; Age; Kidney
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/0047-6374(91)90099-L

Rodent tissues display species-, strain-, sex- and tissue-specific adduct-like DNA modifications termed I-compounds, which increase with age, are modulated by diet and are presumably derived from indigenous metabolic intermediates. We have explored whether I-compounds are affected by caloric restriction, which is known to extend life span and retard age-related degenerative and neoplastic diseases. Male Brown-Norway rats were fed NIH-31 diet ad libitum (AL). Calorically restricted (CR) rats received 60% of AL consumption, starting at 3.5 months. DNA was analyzed by 32P-postlabeling at 1, 4, 8, 12, 16 and 24 months of age in liver, kidney and white blood cells. I-compounds in AL liver and kidney exhibited complex tissue-specific profiles; I-compound levels increased with age, plateaued between 8 and 18 months depending on tissue and diet and were 8.7 (liver) and 27.4 (kidney) modifications in 10 8 nucleotides at 24 months, thereby exceeding the corresponding 1-month values by 3.7- and 16.6-fold. CR resulted in similar profiles but did not diminish age-related increases, rather I-compound levels in CR liver and kidney were increased by about 70% and 30% versus age-matched AL rats. White blood cells exhibited few I-compounds and at low levels; age-related increases were small overall but more pronounced in CR rats. Higher I-compound levels in CR animals, which were presumably a consequence of metabolic effects elicited by CR, thus correlated with extended life span and, therefore, may be beneficial, in agreement with previous findings showing an association between reduced I-compound levels and hepatocarcinogenesis as well as organ susceptibility to diseases.