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Calorie Restriction and BenaGeneTM: The Key to Longevity?

Key Terms

Calorie Restriction (CR)
A dietary regimen that reduces the caloric intake of an individual without resulting in malnutrition or a reduction in the intake of essential nutrients.

NAD+/NADH Ratio A high NAD+/NADH ratio increases the stimulation of a variety of genes in the mitochondria and is associated with high energy production. CR and BenaGeneTM both increase the NAD+/ NADH ratio.

What is Calorie Restriction?

Increasing longevity (or life span) is often considered  nothing  more  than  the  goal  of fictional mad scientists and sorcerers. However, caloric restriction (CR) has been extensively studied over the last 70 years, with numerous studies suggesting that a reduction in total calorie intake by 30% to 50%, can significantly extend one’s lifespan. Simply put, CR is a dietary regimen that reduces the caloric intake of an individual, without resulting in malnutrition or a reduction in the intake of essential nutrients.

In addition to  increasing longevity, CR has been found to promote improvements in metabolism, e n e r g y production, and delay and reduce the incidence of cancer and diabetes. Currently, the m e c h a n i s m by which CR extends life remains to be elucidated, but continues to  be a major focus of the scientific community.

In        addition, the focus has also shifted to the  discovery of products that can  be  taken to mimic the effects of CR, for longevity and also for the treatment of diseases.

How does CR work?

Whilst a reduction in free radicals was originally suggested as a potential mechanism of action of CR, the common consensus now is that CR is linked to energy production mechanisms of mitochondria. The key role of mitochondria is to produce energy (in the form of ATP) for the cell, through a series of complex metabolic processes. One of the key lynch-pins in the mitochondrial energy production processes is a substance  called nicotinamide adenine dinucleotide (NAD). NAD is present in two forms; NAD+ (which is the oxidized form) and NADH, (the reduced form). The NAD+/NADH ratio plays and important role in controlling how much energy the mitochondria produces. Higher NAD+ levels are thought to have a stimulatory effect on anti-aging genes and increase energy production.

On the other hand, high NADH levels limits energy pr oduction. During CR, the NAD +  /NADH ratio is increased, with the oxidized form of NAD being favoured. In a nutshell CR promotes a high NAD +  /NADH ratio, stimulating specific genes, which in turn means  tha t mi t ochon dria increase energy pr oduction. Therefore consuming fewer calories can actually equate to increased energy production!

BenaGeneTM

Despite strong  evidence  showing  that CR can result in increased  lifespan,  many people are unwilling  to  reduce their caloric intake by 30%-50%. As such, the focus has also shifted to identifying CR mimetic (mimicking) agents. One such    promising    agent    is    BenaGeneTM. BenaGeneTM is a thermally stabilized form of oxaloacetate, which is a key intermediate of the energy producing processes of mitochondria. Increasing  oxaloacetate via supplementation has been shown to promote a higher NAD+/NADH ratio, which is associated with all the beneficial effects of CR that we have already discussed. What has scientists and anti-aging enthusiasts so excited is that animal studies have shown that life span was extended by 30% after supplementing  with   BenaGeneTM.   It   has also been shown to induce over 350 anti- aging genes in animals, with a genetic profile similar to CR. Whilst human studies investigating  BenaGeneTM’s  effects  on  life extension have not yet been conducted, human studies have confirmed that BenaGeneTM     supplementation      caused a reduction in glucose levels and an improved uptake of glucose without negative side-effects. Further, BenaGeneTM appears to down-regulate pathways that create and store fat and protects DNA from damage that is thought to exacerbate the aging process. These actions may have tremendous beneficial effects on numerous disease processes such as diabetes and cardiovascular disease.

BenaGeneTM is a thermally stabilized form of oxaloacetate, which is a key intermediate of the energy producing processes of mitochondria. Increasing ox- aloacetate via supplementation has been shown to promote a higher NAD+/NADH ratio, which is associated with all the beneficial effects of CR.

Conclusion

CR has numerous health benefits, including increased longevity and disease prevention. The mechanism of action of CR involves an increase in the NAD+/NADH ratio in the mitochondria, which optimizes energy production and expression of CR genes. Supplementation with a specific stabilized form of oxaloacetate called BenaGeneTM has shown promising positive effects that can mimic the  effect  of  a CR diet. This may translate into clinical applications for almost every chronic disease.

Key Terms

BenaGeneTM

A thermally stable version of oxaloac- etate, which is a CR mimetic (mimick- ing) agent. BenaGeneTM increases the NAD+/NADH ratio, and stimulates many anti-aging genes.

REFERENCE

1. Fontana, et al. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. PNAS. 2004;101(17):6659-6663.

2. Hursting S, et al. Calorie Restriction, Aging and Cancer Prevention: Mechanisms of Action and Applicability to Humans. Annual Review of Medicine. 2003;54:131-152.

3. Lin SJ and Guarente L. Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease. Current Opinion in Cell Biology. 2003;15:241-246.

4. Lin S, et al. Calorie restriction extends yeast life span by lowering the level of NADH”. Genes & Development 2004;18:12-16.

5. Lin SJ. Molecular Mechanisms of Longevity Regulation and Calorie Restriction. In: Kaput J and Rodriguz R. Nutritional Genomics: Discovering the Path to Personalized Nutrition. Wiley and Sons, Inc. NY. 2006.

6. Castro-Marrero J, Cordero MD, Segundo MJ, et al. Does Oral Coenzyme Q10 Plus NADH Supplementation Improve Fatigue and Biochemical Parameters in Chronic Fatigue Syndrome? Antioxidants & Redox Signaling. 2015;22(8):679-685. doi:10.1089/ars.2014.6181.

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