Mitochondrial Ageing and the Beneficial Role of α-Lipoic Acid

Abstract

Oxidative damage has been implicated to be a major causative factor in the decline in physiological functions that occur during the ageing process. Mitochondria are known to be a rich source for the production of free radicals and, consequently, mitochondrial components are susceptible to lipid peroxidation (LPO) that decreases respiratory activity. In the present investigation, we have evaluated mitochondrial LPO, 8-oxo-dG, oxidized glutathione, reduced glutathione, ATP, lipoic acid, TCA cycle enzymes and electron transport chain (ETC) complex activities in the brain of young versus aged rats. In aged rats, the contents of LPO, oxidized glutathione and 8-oxo-dG were high whereas reduced glutathione, ATP, lipoic acid, TCA cycle enzymes and ETC complex activities were found to be low. Lipoic acid administration to aged rats reduced the levels of mitochondrial LPO, 8-oxo-dG and oxidized glutathione and enhanced reduced glutathione, ATP, lipoic acid and ETC complex activities. In young rats lipoic acid administration showed only minimal lowering the levels of LPO, 8-oxo-dG and oxidized glutathione and slight increase in the levels of reduced glutathione, ATP, lipoic acid, TCA cycle enzymes and ETC complex activities. These findings suggest that the dithiol, lipoic acid, provides protection against age-related oxidative damage in the mitochondria of aged rats.

Mitochondrial dysfunction in some oxidative stress-related genetic diseases: Ataxia-Telangiectasia, Down Syndrome, Fanconi Anaemia and Werner Syndrome

“…Pérez et al (2008) showed a decrease in mitochondrial function characterized by a reduction in ATP production from isolated mitochondria and a reduction in the activity of the electron transport chain complexes using mice heterozygous for mitochondrial thioredoxin 2 gene, along with increased ROS production compared to wild type mice, increased oxidative damage to nuclear DNA, lipids, and proteins and more apoptosis in liver. Palaniappan and Dai (2007) and Savitha and Panneerselvam (2007) It is obvious from the previous reports that mitochondria must have a robust endogenous antioxidant enzyme system which can be potentially affected during ageing. Among them, mitochondrial Mn-SOD, peroxiredoxins such as PRDX5, glutathione peroxidase (GPx), and HSP are involved.…”

“…The term ''mitochondrial nutrient'' (Liu 2008) refers to a group of agents that can directly or indirectly protect mitochondria from oxidative damage and improve mitochondrial function (Long et al 2007;Liu 2008;Palaniappan and Dai 2007;Savitha and Panneerselvam 2007;Plecitá-Hlavatá et al 2009). Direct protection includes preventing the generation of oxidants, scavenging free radicals and inhibiting oxidant reactivity, removing oxidized inactive proteins accumulation (Musicco et al 2009), elevating cofactors of defective mitochondrial enzymes, and also protecting enzymes from further oxidation.…”

Effect of Cysteine Derivatives Administration in Healthy Men Exposed to Intense Resistance Exercise by Evaluation of Pro-Antioxidant Ratio

“…α-Lipoic acid is commonly used as a dietary supplement by athletes to increase muscle glucose uptake, improve antioxidant defense, and decrease oxidative damage level. However, most studies concerning the beneficial effects of α-lipoic acid on cell metabolism were observed in in vitro studies or animal models, such as rodents and horses [5][6][7][8][9]. …”

Correlation of Age-Related Metabonomic Changes in 1H NMR Serum and Urine Profiles of Rats with Cognitive Function

“…Forster and associates also found such behavioral deficit in old mice which correlates to the protein oxidation and impaired energy metabolism [44]. Therefore, on the basis available evidences, it may be stated that an impaired TCA cycle and electron transport chain functioning in aged rats may lead to decreased ATP production, resulting in changes in motor functioning, perturbed memory status and other neurobehavioral changes [45].…”