MITOCHONDRIAL-DNA REMAINS INTACT DURING DROSOPHILA AGING, BUT THE LEVELS OF MITOCHONDRIAL TRANSCRIPTS ARE SIGNIFICANTLY REDUCED

It has been suggested that mutations accumulated in mitochondrial DNA during the aging process may be causally related to the decreased phys iological response of the senescent organisms. We have quantified and evaluated the integrity of the mitochondrial genome during the life sp an of Drosophila melanogaster. Its amount remains fairly constant repr esenting roughly 1% of the total DNA at all ages. Southern experiments have also revealed a high stability and integrity of the mitochondria l DNA (mtDNA). However, we have detected an important decrease in the steady-state levels of all mitochondrial transcripts investigated: 16 S ribosomal RNA (16SrRNA), cytochrome c oxidase, cytochrome b, and bet a H+-ATP synthase subunit. These changes correlate with the shape of t he life span curve, preceding the decrease in survival of the male fli es used in the study, and at least in the case of 16SrRNA, is tissue-s pecific. Although mitochondrial DNA remains unchanged in heads, thorac es, and abdomens, 16SrRNA levels decrease more severely in heads and t horaces and much less conspicuously in abdomens. On the other hand, co ntrol non-mitochondrial transcripts investigated remain essentially un affected. These results suggest that in Drosophila the main effect of aging on the mitochondrial genetic system is downstream from mtDNA its elf. The decline in the levels of beta H+-ATPase transcript, nuclear-e ncoded, suggests that not only the mitochondrial machinery, but also t he nuclear one involved in mitochondrial biogenesis, is affected durin g aging.