MEASURING MITOCHONDRIAL DNA DAMAGE IN CAENORHABDITIS ELEGANS, IMPLICATIONS FOR AGEING AND HEALTHSPAN

Abstract

THE MITOCHONDRIAL FREE RADICAL THEORY OF AGEING (MFRTA) PROPOSES THAT LOSS OF MITOCHONDRIAL DNA (MTDNA) INTEGRITY AS RESULT OF DAMAGE BY ENDOGENOUS REACTIVE OXYGEN SPECIES (ROS) IS A MAJOR CAUSE OF AGE-DEPENDENT MITOCHONDRIAL DEGENERATION. I HAVE DEVELOPED A SENSITIVE S-XL-QRT-PCR DNA DAMAGE ASSAY THAT CAN MEASURE DNA DAMAGE IN CAENORHABDITIS ELEGANS (C. ELEGANS), PARTICULARLY MTDNA. I FOUND THAT MTDNA DAMAGE IN C,ELEGANS IS USUALLY LOW, IN THE ORDER OF LESS THAN ONE LESION PER MOLECULE OF MTDNA. THIS LOW LEVEL OF MTDNA DAMAGE IS PROBABLY NOT SUFFICIENT TO INTERFERE SIGNIFICANTLY WITH MITOCHONDRIAL FUNCTION TO PLAY A PART IN REDUCING THE LIFESPAN OF THE NEMATODES. PHARMACOLOGICAL INTERVENTIONS USING A MITOCHONDRIAL TARGETED ANTIOXIDANT, MITOQ DO NOT ALTER THE MTDNA DAMAGE OF A TRANSGENIC C. ELEGANS MODEL OF ALZHEIMER DISEASE DESPITE AN INCREASE IN THE LIFESPAN AND HEALTHSPAN OF THE NEMATODES. IN FACT, I FOUND THAT THE PROTECTIVE EFFECT IN LIFESPAN AND HEALTHSPAN MAY BE CAUSED BY HIGHLY