Mitochondrial and nuclear DNA base excision repair are affected differently by caloric restriction

  title={Mitochondrial and nuclear DNA base excision repair are affected differently by caloric restriction},
  author={Jeff A. Stuart and Bensu Karahalil and Barbara A. Hogue and N C Souza-Pinto and Vilhelm A. Bohr},
  journal={The FASEB Journal},
Aging is strongly correlated with the accumulation of oxidative damage in DNA, particularly in mitochondria. Oxidative damage to both mitochondrial and nuclear DNA is repaired by the base excision repair (BER) pathway. The “mitochondrial theory of aging” suggests that aging results from declining mitochondrial function, due to high loads of damage and mutation in mitochondrial DNA (mtDNA). Restriction of caloric intake is the only intervention so far proven to slow the aging rate. However, the… 

In vitro measurement of DNA base excision repair in isolated mitochondria.

This chapter outlines the step-by-step protocols for isolating mitochondrial fractions, from a number of different model organisms, of sufficient purity to allow mtDNA repair activities to be measured, and details in vitro assays for the measurement of BER enzyme activities in lysates prepared from isolated mitochondria.

Mitochondrial DNA repair and association with aging – An update

Activities of DNA base excision repair enzymes in liver and brain correlate with body mass, but not lifespan

Testing whether an enhancement of BER enzyme activities has occurred concomitantly with the evolution of increased maximum lifespan (MLSP) found nucleotide incorporation and oligonucleotide ligation activities appeared to be primarily (and negatively) correlated with species body mass.

Creatine supplementation normalizes mutagenesis of mitochondrial DNA as well as functional consequences.

Increases in intracellular creatine levels indicate that increase of the energy precursor creatine protects from functionally relevant, aging-associated mutations of mitochondrial DNA.

Dietary Restriction at Old Age Lowers Mitochondrial Oxygen Radical Production and Leak at Complex I and Oxidative DNA Damage in Rat Brain

The results agree with the idea that CR decreases aging rate in part by lowering the rate of free radical generation of mitochondria in the brain.

Aging and Calorie Restriction Oppositely Affect Mitochondrial Biogenesis through TFAM Binding at Both Origins of Mitochondrial DNA Replication in Rat Liver

An age-related decrease in mitochondrial DNA content and mitochondrial transcription factor A amount was found and a marked increase in the TFAM-bound amounts of mtDNA at both origins of replication with aging, fully prevented by CR.

Expression changes in DNA repair enzymes and mitochondrial DNA damage in aging rat lens

The experiments demonstrated that the gene expression of mRNA and protein in these key BER enzymes decreased with age, which caused a decrease in the repairing capability of the mtDNA and the accumulation of mtDNA damage.



Base excision repair capacity in mitochondria and nuclei: tissue‐specific variations

There was no correlation between glycosylase activities in the mitochondrial extracts and COX activity, suggesting that DNA repair enzymes may be regulated by a mechanism different from this mitochondrial enzyme.

Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals

  • G. BarjaA. Herrero
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2000
The results obtained agree with the notion that oxygen radicals of mitochondrial origin oxidatively damage mtDNA in a way related to the aging rate of each species.

Multi-organ characterization of mitochondrial genomic rearrangements in ad libitum and caloric restricted mice show striking somatic mitochondrial DNA rearrangements with age.

Observations confirm that mtDNA mutations accumulate with age in mice and suggest that caloric restriction impedes this progress, which is suggested to extend life span supporting an association between bioenergetics and senescence.

Caloric restriction decreases mitochondrial free radical generation at complex I and lowers oxidative damage to mitochondrial DNA in the rat heart

The results are consistent with the concept that CR decreases the aging rate at least in part by decreasing the rate of mitochondrial oxygen radical generation and then the rates of attack on mtDNA.

Mouse models of mitochondrial disease, oxidative stress, and senescence.

Age-associated change in mitochondrial DNA damage.

These findings agree with other reports showing an age-associated increase in levels of mtDNA damage; however, the degree to which it increases is smaller.

Upregulation of Mitochondrial Base-Excision Repair Capability within Rat Brain after Brief Ischemia

Differences in BER capacity after brief or prolonged ischemia are revealed, which may contribute to the neuron's ability to resist subsequent ischemic insults.