ReviewOptimal micronutrients delay mitochondrial decay and age-associated diseases
Section snippets
Lipoic acid and acetyl carnitine supplements decrease the mitochondrial decay of aging
Mitochondrial decay appears to be a major contributor to aging and its associated degenerative diseases including cancer and neural decay (Shigenaga et al., 1994, Beckman and Ames, 1998). Mitochondria from old rats compared with those from young rats generate increased amounts of oxidant by-products (Hagen et al., 2002a), and have decreased membrane potential, respiratory control ratio, cellular oxygen consumption, and cardiolipin (a key lipid found in mitochondria). Oxidative damage to DNA,
Triage theory suggests a cause of much preventable aging-associated disease
The “triage theory” (Ames, 2006, Ames and McCann, 2009) provides a unifying rationale for a causal link between deficiency of a micronutrient (∼40 essential minerals, vitamins, amino acids and fatty acids) and the many degenerative diseases accompanying aging such as cancer, immune dysfunction, cognitive decline, cardiovascular disease, and stroke. These diseases might be delayed by an inexpensive micronutrient intervention (Ames and McCann, 2009).
Triage theory (Ames, 2006, Ames and McCann, 2009
Enzymes lose binding affinity (increased Km) for coenzymes and substrates with mutation or age: a strategy for remediation with high dose vitamins
A review (Ames et al., 2002) showed that about 50 human genetic diseases due to defective enzymes can be remedied or ameliorated by the administration of high doses of the vitamin component of the corresponding coenzyme, which at least partially restores enzyme activity. Up to a quarter of mutations in a gene result in the corresponding enzyme having a decreased binding constant (increased Km) for a coenzyme resulting in a lower rate of reaction. The review points out that many of the B
Conclusion
The work on acetyl carnitine and lipoic acid in rodents and dogs suggests that decay of mitochondria leading to dementia and a variety of other diseases of aging in humans is not inevitable, but may be delayed by various interventions to improve metabolism. Understanding the mechanisms will suggest still other interventions. For example, if lipoic acid is effective because it induces the ∼200 enzymes in the phase-2 defense system against oxidants, as seems likely, then the whole area of
Conflict of interest
Dr. Ames is one of the founders of Juvenon (www.juvenon.com), a company that has licensed the University of California patent on acetyl carnitine + lipoic acid for rejuvenating old mitochondria (Ames and T. Hagen, inventors), sells acetyl carnitine + lipoic acid supplements, and does clinical trials on them. Ames founder's stock was put in a non-profit foundation at the founding in 1999. He is director of Juvenon's Scientific Advisory Board, but reimbursement for that from Juvenon is given to the
Acknowledgements
We are indebted to T. Hagen, D. Killilea, J. Liu, J. McCann, S. Shenvi, and J. Suh for helpful criticisms and to the many excellent students and colleagues who have contributed to this work.
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2017, Experimental GerontologyCitation Excerpt :In addition to ALCAR treatment alone, this compound has been used in combination with other substances that improve mitochondrial metabolism and reduce oxidative stress. In particular, Ames's group reported that the combined treatment of ALCAR and lipoic acid ameliorated mitochondrial function in different tissues (expecially brain and heart) of old rats, by protecting from oxidative stress and improving several metabolic and structural parameters (Aliev et al., 2009; Ames and Liu, 2004; Ames, 2010; Hagen et al., 2002a, 2002b; Long et al., 2009). Results from the present study show dietary ALCAR supplementation counteracted the age-related alterations of mitochondrial biogenesis and dynamics in the rat cerebellum and cerebral hemispheres.
Nutrition and energetics in rodent longevity research
2016, Experimental GerontologyCitation Excerpt :Typical diets in free-living conditions are compositionally diverse with foods most often providing complex mixtures of macronutrients of varying proportions, increasing the complexity and difficulty of assimilating nutrition research findings (laboratory and field based) into the overall study of nutritional energetics. Another layer of complexity arises with the addition of multiple micronutrients and essential factors that provide limited (or no) overall energetic value yet can impact the cell and organism's ability to properly metabolize nutrients containing caloric value (Ames, 1998, 2005, 2010). When considered then in the context of organisms' changing energetic demands coincident with fundamental nutrient requirements at different ages, varying levels of physical activities, various body compositions, etc., the desire or quest for identifying an optimized “one size fits all” diet to promote health and longevity seems daunting at best.