AgeLoc Youth – The New Nutritional Supplement From Pharmanex
Louis B. Cady, M.D. – Cady Wellness Institute www.cadywellness.com
AgeLoc Youth is a new and revolutionary supplement from Pharmanex/NuSkin based on modulation of gene expression. It appears to be able to decrease pain and inflammation, decrease cellular aging damage, and improve cognition using a well tolerated, all natural dietary supplement. Full data and background follow in this white paper.
The clinical “DNA” of this product comes from the original Pharmanex company, pioneered by Dr. Joseph Chang, Dr. Michael Chang, and Dr. Carl Djesrrasi. Dr. Joseph Chang is a medicinal chemist who worked at Wyeth-Ayerst, among other companies, and developed Rapamune – an anti-rejection drug which continues to pay dividends. Pharmanex, in contrast to “big pharma” companies, focused on using plants and ethnobotany to improve human health. Their first product was a natural cholesterol-lowering agent. Other products that were in their inventory included a high potency Gingko and an extremely high potency and pure Green Tea extract. These supplements were sold in health food stores nationally. I actually recall buying “TeGreen” at Adele’s Health Food Store here in Evansville in the early 1990’s.
As good as they were, however, they couldn’t compete with other products in terms of flashy packaging or cut-rate prices. An opportunity developed for both Pharmanex and NuSkin Enterprises to merge their resources. NuSkin bought Pharmanex. In October 1998, NuSkin acquired Pharmanex including all of their top talent, Ph.D.’s, and patents. In the first month of operation with a new distribution model, more Pharmanex products were sold than in the previous 12 months of Pharmanex as an independent company.
NuSkin subsequently obtained all patent and licensing rights to the Biophotonic Scanner in 2001. This technology later earned them the American Business Award for Innovative Technology in 2005. The scanner has been an integral part of the nutritional assessments we do at Cady Wellness Institute since 2006.
ACQUISITION OF LIFEGEN TECHNOLOGIES AND INTEGRATION OF GENE EXPRESSION WORK
In 2011, NuSkin acquired LifeGen Technologies in Madison, Wisconsin for 11.7 million dollars, including all of their patents, proprietary tissue bank, gene expression database, and all intellectual property. The cofounders of this company Dr. Richard Weindruch, Ph.D., and Tomas Prolla, Ph.D. were also retained in consulting agreements. The reason for the acquisition was simple. LifeGen is the world leader in gene expression related to interventions in aging, including three decades of work and data on caloric restriction as the only previously identified intervention to extend life and delay aging. This acquisition fit nicely with the Pharmanex model of using all natural substances to support the structure and function of the human body.
Technically, DNA is harvested from living cells, plated out on a DNA “chip” such as the Affymetrix chip system (www.affymetrix.com ) , and then the DNA is exposed to certain natural substances of interest. Genetic expression conclusions are obtained, and product formulation commences.
EVOLUTION OF AGELOC PRODUCTS
The first use of this technology was in the evaluation of genes related to mitochondrial energy production. The relevance of this was that the largest concentrations of mitochondria are in heart, brain, and liver. The focus of this product was increasing mitochondrial function (essentially, ramping up the production of energy at the cellular level) by changing gene expression. The reason for this product was to improve sexual, physical, and cognitive vitality and it has succeeded in these domains. . Two of the three ingredients used showed specific genetic expression changes: from the pattern of genes that switched on and the genes that are switched off in OLD cells compared to the pattern of gene expression in YOUNG cells. An interesting and compelling video showing the obvious difference in genetic expression may be found by going to www.youtube.com and typing in – “Ageloc vitality mouse.” I have personally been on it since it came out and I can vouch for its efficacy – as any patients that I have seen around 6:30 or 7 pm at night will attest.
This product, good as it was, involved changing the genetic expression of around 40 or so genes. Here is a pictorial description of the gene reset pattern using Cordyceps Sinensis Cs-4 – one of the three ingredients in Ageloc Vitality. It is relevant for this discussion because it shows the evolution of gene expression technology (“Epigenetics”) that is at the core of LifeGen Technologies and its partnership now with Nuskin/Pharmanex. You can see that the genetic expression of old genes is reset to rather closely correspond to genetic expression in younger mitochondrial cells.
Transcriptional Biomarkers of Mitochondrial Aging and Modulation by Cordyceps Sinensis Cs-4. Gordon Research Conference, Biology of Aging, Determinants of Health-Span: From Cells to Humans, August 22-27, 2010. Les Diablerets Conference Center, Les Diablerets, Switzerland.
The second “Age Loc’ed” product was TR-90 – a product that reset genetic expression of fat cells. It essentially transformed the genetic expression back to a more youthful one in your 20’s where you burned fat more easily and stored it less easily. This is the product that I personally used to lose 10 lbs and a significant amount of body fat – easily and painlessly – in three months. This product was, however, very targeted and affected only the expression of genes related to fat cells and metabolism.
AgeLoc Youth – what’s different? What are the studies that support its use?
Age Loc YOUTH resets the genetic expression of approximately 1000 genes to a more youthful expression and is the culmination of thirty years of epigenetic research. According to the labeling for this product, it targets “aging defense mechanisms” throughout the body.
This product was formulated with a complete peer-reviewed literature review looking at plant-based phytochemicals with distinct and unarguable anti-aging benefits and with an excellent safety profile. Further, these phytochemicals had to be able to be delivered in a dose-appropriate and effective concentration in a dietary supplement. The ingredients were screened genetically using the Affymetrix gene chip (or similar technology) and using caloric restriction as a positive control. The substantiation document that established the scientific validity of the ingredients selected referenced 400 studies, including human trials, in phytochemicals with dosing consistent with what ultimately was included in the AgeLoc Youth formula. The entire world was scoured for relevant compounds.
In the Appendix, which follows – you will find an ingredient list and the exact milligrams of each. Even though one would wonder, for example, what 30 mg of Coenzyme Q10 for a full daily dosage (four capsules) would do, it is the synergy of these ingredients that allows less than heroic dosages for all ingredients used. Furthermore, the synergy of these ingredients – and the efficacy of the formulation has been doubly evaluated using not only gene chip technology but placebo controlled human trials..
There are three areas of study that are either underway or have been accomplished. Their results have not been published (yet), so there is limited “hard core” data. However, in broad brush strokes, here they are.
The first studies were preclinical.
The initial study looked at proof of concept. According to Dr. Angela Mastaloudis, Ph.D., the original studies looked at the absorption of the polyphenolic compounds – compounds that were actually rapidly metabolized and poorly absorbed. Various doses in humans were tested, looking at kinetics. What was found was that the compounds selected were well absorbed, but rapidly metabolized. This provided the underlying scientific basis on pharmacokinetics in terms of why one needs to take this supplement on a twice daily dosing. The specified dosage is two capsules at breakfast and dinner (or “supper”),and with meals. Another preclinical study looked at how well the supplement protected against inflammation and cellular damage. A model of NC2 human skin was used, pretreated with AgeLoc Youth, and exposed to intense UV light. A 50% reduction in the number of damaged cells based on skin biopsy was found – comparing baseline damage and damage at 8 weeks, and evaluating no treatment vs. AgeLoc Youth treatment. A substantial and statistically significant amount of reduced damage at all three dosings of UV radiation (low, medium, and high) was found with AgeLoc Youth. The manuscript for this study is actually submitted for publication and is expected to be published by the end of this year (2015).
The second area of study looked at inflammatory pathways. In this study, which was done with four groups (young control group, old control group, ageLOC blend group, and old group but with the anti-aging intervention caloric restriction), better results than anticipated were shown. The gene expression of ageLOC subjects was actually better (more “youthful”) than the caloric restriction group (a new and unusual finding), and was most like the youthful group. AgeLOC Youth created a 6-fold decrease in the typical increased inflammation pathway that happens with age. In clinical reality, one would believe that this will vastly decreased pain, soreness, and inflammation.
The third area of study is the one that I am most personally and professionally excited about. This was a six week long study – done in a placebo controlled, randomized manner comparing AgeLoc Youth vs. placebo. Functional MRI changes were used as primary endpoint. The study subjects ranged from 40 – 65 years of age. They were tested prior to the study and determined to have normal cognitive functioning. No other nutritional products were consumed during this study. They had diverse diets, and most were basically eating the average American diet.
Comparing baseline and findings 6 weeks after commencing the study:
- Radically improved functional MRI images.
Concomitant, improved cognitive performance on a memory test.
This indicated that not only was there a change in brain activation, but that this increase in brain activation actually corresponded with the neuropsychological expectations of improvement seen on the cognitive testing. These improvements were true for peripheral and internal brain activation in cortical and sub-cortical regions.
This study’s data will be completely analyzed by the end of this year and published in 2016.
The following image is a low-resolution screen shot of the pre- and post- functional MRI images shared during a webinar given recently by Dr. Joseph Chang, the Chief Scientific Officer at Nuskin/Pharmanex. It clearly shows changes in activation of cortex and increased brain activity. The red areas at baseline show areas of decreased brain function, and the areas in green (post-supplementation) show areas of increased brain function. Of particular interest to me is increased activity in the inferior orbital pre-frontal cortex – which is the executive control center of the brain and which is universally compromised in attention deficit disorder, as well as in people who have poor executive functioning.
From what I can see on these functional MRI images, globally improved cognition, memory, reasoning, and executive function should be achieved. It is, however, not a drug; it is only a supplement. Its function is to support the structure and function of the human body. In my opinion, it does so elegantly and naturalistically – with plant based compounds and not synthetic chemicals or pharmaceuticals.
 This is accepted scientific practice, even though you may not have heard of it. An early use was by Bower P, and colleagues, in BMC Genomics. 2006;7:251. “Comparative genomics of fungal allergens and epitopes show widespread distribution of closely related allergen and epitope orthologues.” This study basically looked at the specific genes expressed by different yeast species, and was read out on a gene chip or analogous technology.
 An example of this in human genes is the investigation by Dean Ornish and colleagues, published in the Proceedings of the National Academy of Sciences, USA, 2008 on “Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention.” Specific citation: Ornish, Dean et al. Proc Natl Acad Sci USA 2008 June 17; 105(24): 8369-8374. Essentially, Dr. Ornish was able to switch off cancer gene expressions by an intensive change in nutrition – involving moving away from a highly processed food diet to one rich in fruits and vegetables.
 Angela Mastlaoudis, Ph.D. – Senior Scientist, Global Research and Development, Pharmanex. Reference: https://www.nuskin.com/content/dam/nse/pdf/Bios/angelamastaloudis.pdf accessed November 3, 2015.
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