Optimal micronutrients delay mitochondrial decay and age-associated diseases.
ABSTRACT Three of our research efforts are reviewed, which suggest that optimizing metabolism will delay aging and the diseases of aging in humans. (1) Research on delay of the mitochondrial decay of aging by supplementing rats with lipoic acid and acetyl carnitine. (2) The triage theory, which posits that modest micronutrient deficiencies (common in much of the population) accelerate molecular aging, including mitochondrial decay, and supportive evidence, including an analysis in depth of vitamin K, that suggests the importance of achieving optimal micronutrient intake for longevity. (3) The finding that decreased enzyme binding constants (increased Km) for coenzymes (or substrates) can result from protein deformation and loss of function due to loss of membrane fluidity with age, or to polymorphisms or mutation. The loss of enzyme function can be ameliorated by high doses of a B vitamin, which raises coenzyme levels, and indicates the importance of understanding the effects of age, or polymorphisms, on micronutrient requirements.
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ABSTRACT: I review three of our research efforts which suggest that optimizing micronutrient intake will in turn optimize metabolism, resulting in decreased DNA damage and less cancer as well as other degenerative diseases of aging. (1) Research on delay of the mitochondrial decay of aging, including release of mutagenic oxidants, by supplementing rats with lipoic acid and acetyl carnitine. (2) The triage theory, which posits that modest micronutrient deficiencies (common in much of the population) accelerate molecular aging, including DNA damage, mitochondrial decay, and supportive evidence for the theory, including an in-depth analysis of vitamin K that suggests the importance of achieving optimal micronutrient intake for longevity. (3) The finding that decreased enzyme binding constants (increased Km) for coenzymes (or substrates) can result from protein deformation and loss of function due to an age-related decline in membrane fluidity, or to polymorphisms or mutation. The loss of enzyme function can be compensated by a high dietary intake of any of the B vitamins, which increases the level of the vitamin-derived coenzyme. This dietary remediation illustrates the importance of understanding the effects of age and polymorphisms on optimal micronutrient requirements. Optimizing micronutrient intake could have a major effect on the prevention of cancer and other degenerative diseases of aging.Journal of nucleic acids 09/2010; 2010. DOI:10.4061/2010/725071
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ABSTRACT: Previously we showed that in vivo treatment of elderly Fisher 344 rats with acetylcarnitine abolished the age-associated defect in respiratory chain complex III in interfibrillar mitochondria and improved the functional recovery of the ischemic/reperfused heart. Herein, we explored mitochondrial protein acetylation as a possible mechanism for acetylcarnitine's effect. In vivo treatment of elderly rats with acetylcarnitine restored cardiac acetylcarnitine content and increased mitochondrial protein lysine acetylation and increased the number of lysine-acetylated proteins in cardiac subsarcolemmal and interfibrillar mitochondria. Enzymes of the tricarboxylic acid cycle, mitochondrial β-oxidation, and ATP synthase of the respiratory chain showed the greatest acetylation. Acetylation of isocitrate dehydrogenase, long-chain acyl-CoA dehydrogenase, complex V, and aspartate aminotransferase was accompanied by decreased catalytic activity. Several proteins were found to be acetylated only after treatment with acetylcarnitine, suggesting that exogenous acetylcarnitine served as the acetyl-donor. Two-dimensional fluorescence difference gel electrophoresis analysis revealed that acetylcarnitine treatment also induced changes in mitochondrial protein amount; a two-fold or greater increase/decrease in abundance was observed for thirty one proteins. Collectively, our data provide evidence for the first time that in the aged rat heart in vivo administration of acetylcarnitine provides acetyl groups for protein acetylation and affects the amount of mitochondrial proteins. Copyright © 2015. Published by Elsevier Ireland Ltd.Mechanisms of Ageing and Development 02/2015; 145. DOI:10.1016/j.mad.2015.01.003 · 3.51 Impact Factor
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ABSTRACT: While tissue dysfunction is a well-recognized consequence of diabetes mellitus in aged people, the underlying mechanisms are poorly understood. Daily (VCE) supplementation of vitamins C and E can be beneficial to diabetic aged animals in reducing free radical production. The aim of this study was to investigate whether dietary VCE supplementation modulates oxidative stress and antioxidant redox systems in streptozotocin (STZ)-induced aged diabetic rats. Thirty aged rats (18 - 20 months) were randomly divided into three groups. The first group acted as a control and the second group was diabetic. VCE-supplemented feed was given to aged, diabetic rats, constituting the third group. Diabetes was induced using a single dose of intraperitoneal STZ. On the 21(st) day after STZ dosage, blood and tissue samples were taken from all animals. Glutathione peroxidase activity in liver, erythrocytes, muscle, and testes; catalase activity in plasma and erythrocytes; reduced glutathione levels in plasma; vitamin E concentration in plasma, liver, and muscle; b-carotene concentration in brain; and high-density lipoprotein (HDL)-cholesterol levels in plasma were lower in the diabetic group than in the control group. Lipid peroxidation (LP) levels in plasma, liver, brain, and muscle, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), triacyglycerols, and total and low-density lipoprotein (LDL)-cholesterol values in plasma were higher in the diabetic group than in the control group. The LP, enzyme, vitamin, and lipid profile values levels were mostly restored by VCE treatment. Liver and testis weights did not change by diabetic status and VCE supplementation, although body weight was lower in the diabetic group than in the control group. In conclusion, brain, liver, and testes tissues seem most sensitive in aged diabetic rats to oxidative stress. We observed that VCE supplementation relieves oxidative stress in the blood and tissues of diabetic aged rats by modulating the antioxidant system and lipid profile.International Journal for Vitamin and Nutrition Research 11/2011; 81(6):347-57. DOI:10.1024/0300-9831/a000083 · 1.00 Impact Factor