PMID- 7677927 OWN - NLM STAT- MEDLINE DCOM- 19921222 LR - 20190702 IS - 0027-5107 (Print) IS - 0027-5107 (Linking) VI - 295 IP - 1 DP - 1993 Jan TI - Enhancement of age-related increases in DNA I-compound levels by calorie restriction: comparison of male B-N and F-344 rats. PG - 31-46 AB - Caloric restriction (CR), known to extend median and maximum life spans, improve resistance to carcinogenesis, and significantly retard age-associated degenerative diseases in rodents, was previously reported to modulate levels of indigenous, age-dependent DNA modifications, called I-compounds, in male Brown-Norway (B-N) rats. Since profiles of these adduct-like derivatives are species-, strain-, sex-, and tissue-specific, we explored this apparent CR/I-compound relationship in a comparative study between male B-N and male Fischer 344 (F-344) rats, the latter having a shorter life expectancy and high incidence of renal disease. Control animals were fed NIH-31 diet ad libitum (AL), while the caloric intake of CR animals was limited to 60% of AL, starting at 3.5 months. Liver and kidney DNA from 1, 8, 12, 16, 24 (AL, CR), and 30 (CR only) month old rats was analyzed by 32P-postlabeling. Corresponding tissues from the two strains yielded similar DNA profiles. Total liver I-compound levels displayed 2.3-4.6-fold age-dependent increases from 1 to 24 months, and kidney values at 24 months were 5.2-8 times higher than those at 1 month. In both strains, I-compound levels of CR animals were higher, up to 2-fold, than in age-matched AL rats. Regression analyses indicated linear relationships between most CR relative adduct labeling values (both total and individual fractions) and age, whereas many AL values exhibited this type of link with log age. These findings confirm that a correlation exists between CR and I-compound levels, and, given the above physiological benefits of CR, indicate that I-compounds represent biomarkers of aging with potential utility in intervention studies. FAU - Randerath, K AU - Randerath K AD - Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030. FAU - Hart, R W AU - Hart RW FAU - Zhou, G D AU - Zhou GD FAU - Reddy, R AU - Reddy R FAU - Danna, T F AU - Danna TF FAU - Randerath, E AU - Randerath E LA - eng GR - R01 AG 07750/AG/NIA NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Mutat Res JT - Mutation research JID - 0400763 RN - 9007-49-2 (DNA) SB - IM MH - Aging/*metabolism MH - Animals MH - DNA/*metabolism MH - *DNA Damage MH - Energy Intake MH - *Food Deprivation MH - Kidney/metabolism MH - Liver/metabolism MH - Male MH - Rats MH - Rats, Inbred F344 EDAT- 1993/01/01 00:00 MHDA- 1993/01/01 00:01 CRDT- 1993/01/01 00:00 PHST- 1993/01/01 00:00 [pubmed] PHST- 1993/01/01 00:01 [medline] PHST- 1993/01/01 00:00 [entrez] AID - 0921-8734(93)90009-R [pii] AID - 10.1016/0921-8734(93)90009-r [doi] PST - ppublish SO - Mutat Res. 1993 Jan;295(1):31-46. doi: 10.1016/0921-8734(93)90009-r.