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Caloric restriction promotes genomic stability by induction of base excision repair and reversal of its age-related decline.
- Source :
-
DNA repair [DNA Repair (Amst)] 2003 Mar 01; Vol. 2 (3), pp. 295-307. - Publication Year :
- 2003
-
Abstract
- Caloric restriction is a potent experimental manipulation that extends mean and maximum life span and delays the onset and progression of tumors in laboratory rodents. While caloric restriction (CR) clearly protects the genome from deleterious damage, the mechanism by which genomic stability is achieved remains unclear. We provide evidence that CR promotes genomic stability by increasing DNA repair capacity, specifically base excision repair (BER). CR completely reverses the age-related decline in BER capacity (P<0.01) in all tissues tested (brain, liver, spleen and testes) providing aged, CR animals with the BER phenotype of young, ad libitum-fed animals. This CR-induced reversal of the aged BER phenotype is accompanied by a reversal in the age-related decline in DNA polymerase beta (beta-pol), a rate-limiting enzyme in the BER pathway. CR significantly reversed the age-related loss of beta-pol protein levels (P<0.01), mRNA levels (P<0.01) and enzyme activity (P<0.01) in all tissues tested. Additionally, in young (4-6-month-old) CR animals a significant up-regulation in BER capacity, beta-pol protein and beta-pol mRNA is observed (P<0.01), demonstrating an early effect of CR that may provide insight in distinguishing the anti-tumor from the anti-aging effects of CR. This up-regulation in BER by caloric restriction in young animals corresponds to increased protection from carcinogen exposure, as mutation frequency is significantly reduced in CR animals exposed to either DMS or 2-nitropropane (2-NP) (P<0.01). Overall the data suggest an important biological consequence of moderate BER up-regulation and provides support for the hormesis theory of caloric restriction.
- Subjects :
- Aging metabolism
Animals
DNA drug effects
DNA Polymerase beta metabolism
Male
Mice
Mice, Inbred C57BL
Mutagens pharmacology
Mutation
Nitroparaffins pharmacology
Propane pharmacology
Rats
Rats, Inbred F344
Sulfuric Acid Esters pharmacology
Up-Regulation
Aging genetics
Caloric Restriction
DNA Repair physiology
Propane analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1568-7864
- Volume :
- 2
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- DNA repair
- Publication Type :
- Academic Journal
- Accession number :
- 12547392
- Full Text :
- https://doi.org/10.1016/s1568-7864(02)00219-7