Acetyl-L-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the L-carnitine content in the rat heart.

The aging heart displays a loss of bioenergetic reserve capacity partially mediated through lower fatty acid utilization. We investigated whether the age-related impairment of cardiac fatty acid catabolism occurs, at least partially, through diminished levels of L-carnitine, which would adversely affect carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme for fatty acyl-CoA uptake into mitochondria for β-oxidation. Old (24-28 mos) Fischer 344 rats were fed±acetyl-L-carnitine (ALCAR; 1.

Assessment of endoplasmic reticulum glutathione redox status is confounded by extensive ex vivo oxidation.

Glutathione (GSH) and glutathione disulfide (GSSG) form the principal thiol redox couple in the endoplasmic reticulum (ER); however, few studies have attempted to quantify GSH redox status in this organelle. To address this gap, GSH and GSSG levels and the extent of protein glutathionylation were analyzed in rat liver microsomes. Because of the likelihood of artifactual GSH oxidation during the lengthy microsomal isolation procedure, iodoacetic acid (IAA) was used to preserve the physiological thiol redox state.

Dietary supplementation with (R)-alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex.

Accumulation of divalent metal ions (e.g. iron and copper) has been proposed to contribute to heightened oxidative stress evident in aging and neurodegenerative disorders.

Age-related compensatory activation of pyruvate dehydrogenase complex in rat heart.

Mitochondrial uptake and beta-oxidation of long-chain fatty acids are markedly impaired in the aging rat heart. While these alterations would be expected to adversely affect overall pyridine nucleotides, NADH levels do not change significantly with age. This conundrum suggests that specific compensatory mechanisms occur in the aging heart.

Age-related increase in 4-hydroxynonenal adduction to rat heart alpha-ketoglutarate dehydrogenase does not cause loss of its catalytic activity.

4-hydroxynonenal (HNE), a product of omega-6 polyunsaturated fatty acid peroxidation, impairs mitochondrial respiration in vitro by adducting the alpha-ketoglutarate dehydrogenase complex (KGDC) and inhibiting its activity. The present study seeks to define whether aging increases HNE adduction to rat heart KGDC, and whether such adduction impacts KGDC activity. We found that hearts from old rats exhibit significantly (p< or =0.