Restricted accessResearch articleFirst published online 2010-04
Acetyl- l -Carnitine Supplementation to Old Rats Partially Reverts the Age-Related Mitochondrial Decay of Soleus Muscle by Activating Peroxisome Proliferator-Activated Receptor γ Coactivator-1α–Dependent Mitochondrial Biogenesis
The age-related decay of mitochondrial function is a major contributor to the aging process. We tested the effects of 2-month-daily acetyl-l-carnitine (ALCAR) supplementation on mitochondrial biogenesis in the soleus muscle of aged rats. This muscle is heavily dependent on oxidative metabolism. Mitochondrial (mt) DNA content, citrate synthase activity, transcript levels of some nuclear- and mitochondrial-coded genes (cytochrome c oxidase subunit IV [COX-IV], 16S rRNA, COX-I) and of some factors involved in the mitochondrial biogenesis signaling pathway (peroxisome proliferator-activated receptor γ [PPARγ] coactivator-1α [PGC-1α], mitochondrial transcription factor A mitochondrial [TFAM], mitochondrial transcription factor 2B [TFB2]), as well as the protein content of PGC-1α were determined. The results suggest that the ALCAR treatment in old rats activates PGC-1α–dependent mitochondrial biogenesis, thus partially reverting the age-related mitochondrial decay.
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References
1.
MullerFL, LustgartenMS, JangY, RichardsonA, RemmenHV. Trends in oxidative aging theories. Free Rad Biol Med, 2007; 43:477–503.
2.
GadaletaMN, PetruzzellaV, RenisM, FracassoF, CantatoreP. Reduced transcription of mitochondrial DNA in the senescent rat. Tissue dependence and effect of L-carnitine. Eur J Biochem, 1990; 187:501–506.
3.
PetruzzellaV, BaggettoLG, PeninF, CafagnaF, RuggieroFM, CantatoreP, GadaletaMN. In vivo effect of acetyl-L-carnitine on succinate oxidation, adenine nucleotide pool and lipid composition of synaptic and non-synaptic mitochondria from cerebral hemispheres of senescent rats. Arch Gerontol Geriatr, 1992; 14:131–144.
4.
ParadiesG, RuggieroFM, GadaletaMN, QuagliarielloE. The effect of aging and acetyl-L-carnitine on the activity of the phosphate carrier and on the phospholipid composition in rat heart mitochondria. Biochim Biophys Acta, 1992; 1103:324–326.
5.
ParadiesG, RuggieroFM, PetrosilloG, GadaletaMN, QuagliarielloE. Effect of aging and acetyl-L-carnitine on the activity of cytochrome oxidase and adenine nucleotide translocase in rat heart mitochondria. FEBS Lett, 1994; 350:213–215.
6.
ParadiesG, RuggieroFM, PetrosilloG, GadaletaMN, QuagliarielloE. The effect of aging and acetyl-L-carnitine on the function and on the lipid composition of rat heart mitochondria. Ann NY Acad Sci, 1994; 717:233–243.
ParadiesG, PetrosilloG, GadaletaMN, RuggieroFM. The effect of aging and acetyl-L-carnitine on the pyruvate transport and oxidation in rat heart mitochondria. FEBS Lett, 1999; 454:207–209.
9.
HagenTM, IngersollRT, WehrCM, LykkesfeldtJ, VinarskyV, BartholomewJC, SongMH, AmesBN. Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proc Natl Acad Sci USA, 1998; 95:9562–9566.
10.
HagenTM, LiuJ, LykkesfeldtJ, WehrCM, IngersollRT, VinarskyV, BartholomewJC, AmesBN. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci USA, 2002; 99:1870–1875. Erratum in: Proc Natl Acad Sci USA 2002;99:7184.
11.
CassanoP, SciancaleporeAG, PesceV, FluckM, HoppelerH, CalvaniM, MosconiL, CantatoreP, GadaletaMN. Acetyl-L-carnitine feeding to unloaded rats triggers in soleus muscle the coordinated expression of genes involved in mitochondrial biogenesis. Biochim Biophys Acta, 2006; 1757:1421–1428.
12.
MoriggiM, CassanoP, VassoM, CapitanioD, FaniaC, MusiccoC, PesceV, GadaletaMN, GelfiC. A DIGE approach for the assessment of rat soleus muscle changes during unloading: Effect of acetyl-L-carnitine supplementation. Proteomics, 2008; 8:3588–3604.
13.
MusiccoC, CapelliV, PesceV, TimperioAM, CalvaniM, MosconiL, ZollaL, CantatoreP, GadaletaMN. Accumulation of overoxidized Peroxiredoxin III in aged rat liver mitochondria. Biochim Biophys Acta, 2009; 1787:890–896.
14.
ScarpullaRC. Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev, 2008; 88:611–638.
15.
PesceV, CormioA, FracassoF, LezzaAMS, CantatoreP, GadaletaMN. Age-related changes of mitochondrial DNA content and mitochondrial genotypic and phenotypic alterations in rat hind-limb skeletal muscles. J Gerontol A Biol Sci Med Sci, 2005; 60:715–723.
16.
BarazzoniR, ShortKR, NairKS. Effects of aging on mitochondrial DNA copy number and cytochrome c oxidase gene expression in rat skeletal muscle, liver, and heart. J Biol Chem, 2000; 275:3343–3347.
17.
CassanoP, SciancaleporeAG, LezzaAM, LeeuwenburghC, CantatoreP, GadaletaMN. Tissue-specific effect of age and caloric restriction diet on mitochondrial DNA content. Rejuvenation Res, 2006; 9:211–214.
18.
WredenbergA, WibomR, WilhelmssonH, GraffC, WienerHH, BurdenSJ, OldforsA, WesterbladH, LarssonNG. Increased mitochondrial mass in mitochondrial myopathy mice. Proc Natl Acad Sci USA, 2002; 99:15066–15071.
