Effect of Antioxidant Diets on Mitochondrial Gene Expression in Rat Brain During Aging

Abstract

Age-related increase of reactive oxygen species (ROS) is particularly detrimental in postmitotic tissues. Calorie restriction (CR) has been shown to exert beneficial effects, consistent with reduced ROS generation by mitochondria. Many antioxidant compounds also mimic such effects. N-acetyl cysteine (NAC) provides thiol groups to glutathione and to mitochondrial respiratory chain proteins; thus, it may counteract both ROS generation and effects. In the present study we investigated, in different rat brain areas during aging (6, 12, and 28 months), the effect of 1-year treatment with CR and dietary supplementation with NAC on the expression of subunit 39 kDa and ND-1 (mitochondrial respiratory complex I), subunit IV (complex IV), subunit alpha of F0F1-ATP synthase (complex V) and of adenine nucleotide translocator, isoform 1 (ANT-1). The observed age-related changes of expression were prevented by the dietary treatments. The present study provides further evidence for the critical role of mitochondria in the aging process.

The mitochondrial energy transduction system and the aging process

“…N-acetyl cisteine prevented, in rat brain, the aged-related changes in mitochondrial gene expression of subunit 39 kDa and ND-1 of complex I, complex IV, subunit ␣ of F 1 -ATP synthase (complex V) and of adenine nucleotide translocator isoform 1 (119). Ubiquinone supplementation improved mitochondrial function in heart mitochondria of aged rats (122) and melatonin protected hepatic mitochondrial respiratory activity in senescence-accelerated mice (124).…”

Anti-Inflamm-Aging Effects of Long-Term Caloric Restriction via Overexpression of SIGIRR to Inhibit NF-κB Signaling Pathway

“…age-associated molecular, physiological, and pathological processes that occur not only in the kidneys [12] but also in the skeletal muscle, heart and brain [13,14]. Additionally, CR has been shown to effectively reduce chronic progressive nephropathy and ameliorate renal autophagy and oxidative damage in many studies [15,16].…”

Age-related changes in mitochondrial UCP, ANT and COX III gene expression in the breast muscle of quails (Coturnix coturnix japonica)

“…In the present study, we found that older birds displayed a lower ANT mRNA expression in muscle tissue, and poorer feed conversion, just as Ojano-Dirain et al (2007) also reported that birds with a lower ANT expression had a worse feed efficiency due to the lower ATP production efficiency. Nicoletti et al (2005) also found a reduced ANT expression correlated to aging. According to these authors, alterations in the expression of respiratory chain subunits may represent an adaptive cellular response to the accumulated damage to proteins and/or mitochondrial DNA that occurs due to the increased quantity of ROS.…”

“…Ojano-Dirain et al (2007) suggest that a greater ROS production and greater protein oxidation are consistently found in birds with lower feed efficiency, indicating that this factor may alter the expression of mitochondrial genes. Greater production of free radicals and greater protein oxidation are also related to aging (Nicoletti et al, 2005). Barazzoni et al (2000) verified a reduction in COX III mRNA expression related to altered oxidative capacity of mitochondria in older animals.…”

“…AccordAccording to this theory, typical indications of aging are: increased suppression/mutation in mtDNA, overproduction of reative oxygen species (ROS), and increased mitochondrial dysfunction as well (Nicoletti et al, 2005). Oxidative damage and impaired efficiency of the respiratory chain of mitochondria related to aging seem to involve a vicious cycle where mtDNA lesions may affect respiratory chain functioning, such as electron escape, which could lead to higher quantities of ROS and result in more mtDNA lesions (Tengan et al, 1998).…”