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.
"Further studies are needed to define in more detail the mechanism of acetylcarnitine action at the molecular level and to explore the translational aspects of acetylcarnitine treatment. Acetylcarnitine diminishes the aging defect in different tissues (Paradies et al., 1992, 1994, 1995; Hagen et al., 1998; Iossa et al., 2002; Virmani and Binienda, 2004; Virmani et al., 2004; Lesnefsky et al., 2006; Ames, 2010) and has been tested in Clinical Phase I, II, and III studies on humans with no side effects. Since orally administered acetylcarnitine was as effective in increasing the mitochondrial acetylation potential as was intraperitoneal injection, it provides a convenient, non-invasive, and safe way to treat and to prevent the adverse cardiac effects associated with aging. "
"The author is indebted to J. McCann, D. Killilea, S. Shenvi, and J. Suh for helpful criticisms and to the many excellent students and colleagues who have contributed to this work. This paper has been adapted in part from . "
[Show abstract][Hide abstract] 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(1-2). DOI:10.4061/2010/725071
[Show abstract][Hide abstract] ABSTRACT: Rodents are often the species of choice to examine the effect of drugs on survival and on the progression of specific diseased tissues. This statement is also true for research laboratories working in the field of nutrition and aging. In addition to diets that can reduce the life expectancy of rodents, such as diabetogenic or high-fat diets, genetically modified rodents exhibiting different accelerated age-associated diseases also provide important biologic tools to decipher the impact of drugs, nutrients, or phytoactive compounds on their health and life span. This review covers some of the chemicals believed to decelerate the appearance of age-related diseases in different rodent models. Such chemicals include antioxidants, anti-inflammatory molecules, modulators of metabolic sensors, calorie restriction mimetics, and vegetal polyphenolic compounds that affect mitochondrial functions, cellular proliferation or differentiation as well as cell functionality.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 03/2011; 67(2):140-51. DOI:10.1093/gerona/glr038 · 5.42 Impact Factor
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