PMID- 7507561
OWN - NLM
STAT- MEDLINE
DCOM- 19940303
LR  - 20190702
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 295
IP  - 4-6
DP  - 1993 Dec
TI  - Biomarkers of aging: correlation of DNA I-compound levels with median lifespan of 
      calorically restricted and ad libitum fed rats and mice.
PG  - 247-63
AB  - I-compounds are species-, tissue-, genotype-, gender-, and diet-dependent bulky 
      DNA modifications whose levels increase with animal age. While a few of these DNA 
      modifications represent oxidation products, the majority of I-compounds appear to 
      be derived from as yet unidentified endogenous DNA-reactive intermediates other 
      than reactive oxygen species. Circadian rhythms of certain I-compounds in rodent 
      liver imply that levels of these DNA modifications are precisely regulated. 
      Caloric restriction (CR), the currently most effective method available to retard 
      aging and carcinogenesis, has been previously shown to elicit significant 
      elevations of I-compound levels in tissue DNA from Brown-Norway (BN) and F-344 
      rats as compared to age-matched ad libitum fed (AL) animals. The present 
      investigation has extended this work by examining liver and kidney DNA I-compound 
      levels in three genotypes of rats (F-344, BN, and F-344 x BN) and two genotypes 
      of mice (C57BL/6N and B6D2F1) under identical experimental conditions in order to 
      determine whether correlations exist between I-compound levels, measured in 
      middle-aged animals, and median lifespan. Levels of a number of liver and kidney 
      I-compounds were found to display genotype- and diet-dependent, statistically 
      significant positive linear correlations with median lifespan in both species. In 
      particular, the longer-lived hybrid F-344 x BN rats and B6D2F1 mice tended to 
      exhibit higher I-compound levels than the parent strains. CR enhanced I-compound 
      levels substantially in both rats and mice. Thus, I-compounds, measured at middle 
      age, reflected the functional capability ('health') of the organism at old age, 
      suggesting their predictive value as biomarkers of aging. The positive linear 
      correlations between levels of certain I-compounds (designated as type I) and 
      lifespan suggest that these modifications may be functionally important and thus 
      not represent endogenous DNA lesions (type II), whose levels would be expected to 
      correlate inversely with lifespan.
FAU - Randerath, K
AU  - Randerath K
AD  - Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
FAU - Zhou, G D
AU  - Zhou GD
FAU - Hart, R W
AU  - Hart RW
FAU - Turturro, A
AU  - Turturro A
FAU - Randerath, E
AU  - Randerath E
LA  - eng
GR  - P42 ES 04917/ES/NIEHS NIH HHS/United States
GR  - R01 AG 07750/AG/NIA NIH HHS/United States
GR  - R37 CA 32157/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (Nucleotides)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Aging/*genetics
MH  - Animals
MH  - DNA/*metabolism
MH  - *Energy Intake
MH  - Genotype
MH  - Kidney/metabolism
MH  - Life Expectancy
MH  - Liver/metabolism
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Nucleotides/*metabolism
MH  - Rats
MH  - Rats, Inbred Strains
EDAT- 1993/12/01 00:00
MHDA- 1993/12/01 00:01
CRDT- 1993/12/01 00:00
PHST- 1993/12/01 00:00 [pubmed]
PHST- 1993/12/01 00:01 [medline]
PHST- 1993/12/01 00:00 [entrez]
AID - 0921-8734(93)90024-W [pii]
AID - 10.1016/0921-8734(93)90024-w [doi]
PST - ppublish
SO  - Mutat Res. 1993 Dec;295(4-6):247-63. doi: 10.1016/0921-8734(93)90024-w.