Reduced transcription of mitochondrial DNA in the senescent rat

Abstract

A quantitative study on the effect of senescence on mitochondrial D N A expression has been carried out by measuring the levels of the 12s rRNA and of the mRNA for the subunit I of cytochrome oxidase in several tissues of adult and senescent rats. The concentration of both RNA species/mitochondrial DNA molecule is significantly reduced in senescent brain and heart, as opposed to the respective adult tissues. No appreciable variation occurs in the liver. A 1-h pretreatment with acetyl-L-carnitine brings back the level of senescent brain and heart transcripts to that of adult tissues. The same treatment of adult rats does not cause significant changes in mitochondrial RNA content. These results suggest that the age-dependent impairment of both heavy-strand mitochondrial DNA transcription units is related to altered environmental conditions which acetyl-L-carnitine, a substance which acts by stimulating, directly or indirectly, the energy metabolism, is able to remove.

Age- and calorie restriction-related changes in rat brain mitochondrial DNA and TFAM binding

“…The lower binding to the D-loop region, where the two HSP and LSP promoters are localized, could determine a reduced rate of mitochondrial transcription. Interestingly, such an event was described in the cerebral hemispheres of aged rats (Gadaleta et al 1990). Decreased mitochondrial transcription can severely affect the production of the primer for H-strand synthesis and then mtDNA content; this is consistent with the 25 % mtDNA loss that we observed in the aged AL animals.…”

Peroxide accumulation without major mitochondrial alteration in replicative senescence

“…In most studies the steady state level of mitochondrial transcripts was found to decrease with age, in Drosophila [8], in rat [9], in brain [10] but not in skeletal muscle of humans [11]. The lower level of transcripts does not seem to re£ect a change in mtDNA content, controversial observations were made: an increase [4] or a decrease [12] in rat, a stable amount in Drosophila [8].…”

Functional Disorders of the Oxidative Phosphorylation System in the Heart Mitochondria of Mice with Juvenile Visceral Steatosis.

“…However, it is noteworthy that acetyl-L-carnitine has been shown to be able to stimulate the transcription of mitochondrial DNA such as 12S rRNA and the mRNA of subunit I of cytochrome oxidase under altered metabolic conditions such as in hypothyroidism and senescence rats. 32,33) Furthermore, it has recently been reported that the long-chain fatty acids suppress the induction of ureacycle enzyme genes by glucocorticoid action in rat hepatocytes in primary culture. 34) Therefore, it is conceivable that the long-chain fatty acids not metabolized in the heart are involved in the regulation of the expression of mitochondrial proteins such as cytochromes in the heart of JVS mice.…”

“…The reaction was stopped 5 min later by adding 0.2 ml of 40% trichloroacetic acid, and the mixture was then centrifuged at 10000 rpm for 3 min. An aliquot of the supernatant (0.5 ml) was taken for extracting [g-32 P] ATP, and another aliquot was taken for counting total 32 P as described previously. 21) ATPPi exchange activity was expressed as nmol Pi/mg protein/ min.…”

“…20) Briefly, the mitochondria (100 mg of protein) were suspended in 0.5 ml of the oxygraph medium described above containing 5 mM MgCl 2 , 0.08 mg/ml antimycin A, and 32 Pi (2ϫ10 6 cpm), and then the reaction was started in the presence or absence of oligomycin (0.015 mg) by adding 8 mM ATP. The reaction was stopped 5 min later by adding 0.2 ml of 40% trichloroacetic acid, and the mixture was then centrifuged at 10000 rpm for 3 min.…”