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THE NU SKIN OPPORTUNITY

The world’s leading anti-aging company is addressing the sources of aging, not just the signs and symptoms. THE NU SKIN OPPORTUNITY. TRADITION OF INNOVATION. Nu Skin 180 Galvanic Spa Scanner Nano g3 TruFace essence ultra. 2. What is ageLOC?. SIGNS.

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THE NU SKIN OPPORTUNITY

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  1. The world’s leading anti-aging company is addressing the sources of aging, not just the signs and symptoms. THE NU SKIN OPPORTUNITY

  2. TRADITION OF INNOVATION • Nu Skin 180 • Galvanic Spa • Scanner • Nano • g3 • TruFace essence ultra 2

  3. What is ageLOC? SIGNS Developing products that address the sources of aging, not just the signs and symptoms.

  4. ARNOX, AN AGING ENZYME: 1ST AGELOC SOURCE OF AGING D. James Morré, PhDDepartment of Medicinal Chemistry and Molecular Pharmacology andDorothy M. Morré, PhD Department of Foods and Nutrition Purdue University, West Lafayette, Indiana

  5. Identified a NOX which increases with age Nicotinamide adenine dinucleotideOXidase, a hydroquinone oxidase

  6. 1/2 O2 H2O NOX 2 O2 S SH Protein Protein Outside S SH Plasma Membrane Q10 Q10H2 Inside Quinone Reductase NAD(P)+ NAD(P)H + H+ • arNOX Generates Superoxide O2- - 2 O2 A powerful free-radical generator

  7. GENESIS OF AGELOC The arNOX discovery helped explain… Why Some People Look Years Younger Than They Really Are.

  8. HUMAN GENOME • Our genome encodes for: • our looks • our size • how our bodies work • our health • our behaviors • Our longevity

  9. Genes impact structure and function of the body Health or Beauty Index YEARS

  10. After 20 yrs Human Genome Sequenced • 2003 discovery after 20 years of research: 25,000 – 30,000 genes form the human genome • Twenty Labs with hundreds of scientists (United States, the United Kingdom, France, Germany, Japan and China), • $3 billion

  11. GATCGACTCCTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCC---TTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCC---TTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGT AAAGT The Human Genome consistsof at least 25,000 – 30,000 genes

  12. Nu Skin Enterprises Center for Anti-Aging Research (NSE:CAAR)

  13. NSE:CAAR Anti-Aging Genetic Experts Published over 300 scientific papers, and their insights have changed the way aging is viewed. 

  14. NSE: Center for Anti-Aging Research • Experts in the study of the ultimate source of aging; our genes.  • 30 Years of pioneering anti-aging research. • Their work both details the genetic basis of aging, and demonstrates that biological aging is no longer considered an inexorable or inevitable process. 

  15. Genetics 101 nucleus Cell DNA (stored on chromosomes)

  16. ULTIMATE SOURCE OF AGING = GENE EXPRESSION • As you age, your genes don’t change • Which genes are turned on and off does change (e.g. gene expression). • Expression levels are influenced by your environment (stress, nutrition, etc…)

  17. IDENTICAL TWINS ARE DIFFERENT • How is this possible, as their genes are the same? • It turns out that while the genes are identical, the level at which gene is turned on and off changes based on environmental factors (e.g. gene expression). This causes the differences you can see.

  18. Yellow shows where the twins have similar gene regulation. Red and Green indicate differences (up and down regulation).

  19. Elastin arNOX To better understand aging, we need to know the expression level for every gene. …in a single experiment.

  20. Gene Expression Profiling 101 Young Skin Fibroblast (Hypothetical) Gene 1 arNOX Gene 2 Elastin Gene 3 Collagen Gene 4 MMP DNA mRNA Microarray (e.g. Gene Chip) Young Skin Key arNOX (0) Elastin (8) - High Activity - Medium Activity - Low Activity Collagen (6) MMP (2) - Off

  21. Elastin arNOX The expression level for every gene in a single experiment! DNA Microarray Gene Map Key Over 25000 Genes - High Activity - Medium Activity - Low Activity - Off

  22. NuSkinageLOC Approach • Identify Youth Gene Clusters (YGC’s), and understand their youthful expression patterns • Target - Investigate the effect different ingredients have on YGC’s. • Reset - Develop formulae that reset these YGC’s back to their youthful state, thus restoring the youthful biochemistry of a cell.

  23. What is a Youth Gene Cluster (YCG) • These are groups of genes (e.g. clusters) that work together to exert a specific function in a tissue associated with youthfulness. • Tissue specific • Act as master regulators of aging.

  24. Younger Than Chronological Age

  25. In additional to understanding the genetic basis of aging in Humans, mice, fruit flies, yeast and roundworms are also fruitful models for the genetic/aging scientist

  26. Gene Expression Profiling 101 Young Skin Fibroblast (Hypothetical) Gene 1 arNOX Gene 2 Elastin Gene 3 Collagen Gene 4 MMP DNA mRNA Old Skin Fibroblast (Hypothetical) Gene 1 arNOX Gene 2 Elastin Gene 3 Collagen Gene 4 MMP DNA mRNA

  27. Gene Expression Profiling 101 Young Skin Old Skin arNOX (0) Elastin (8) arNOX (8) Elastin (0) Changes with Aging Collagen (6) MMP (2) Collagen (2) MMP (4) By comparing the two, you can understand the genetic changes associated with aging Key - High Activity - Medium Activity Down regulation No Change Up regulation - Low Activity - Off

  28. INTELLIGENT BIOINFORMATICS DATABASE YOUTH GENE CLUSTERS

  29. Map of Aging Genetics (Whole Genome) • Huge Proprietary Database • Over 25 Million aging related genetic changes and growing. • Bio-Informatics on this database yields the genetic map of the aging process • Shows us the path we need to take

  30. ageLOC Process • Identifying Youth Gene Clusters (YGC’s), and understanding their youthful expression level • Targeting - Cataloging the effect different ingredients have on YGC’s. • Resetting - Developing formulas that reset these YGC’s back to their youthful state, thus restoring the youthful biochemistry of a cell.

  31. How Do We Target and Reset YGC’s - Remember the Gene Chip? Key - High Activity DNA Microarray Gene Map - Medium Activity Over 20000 Genes - Low Activity - Off

  32. Identifying Changes (Old vs. Young YGC Profile) Old Skin Young Skin A B A B D C C D By comparing the two, you can understand the genetic changes associated with aging Key - High Activity - Medium Activity - Low Activity - Off

  33. Targeting & Resetting YGC Once you map the changes, you can screen for ingredients and formulas that reverse these changes Young Skin A B Old Skin A B AGING Post Application C D A B ageLOC D C C D Key - High Activity - Medium Activity - Low Activity - Off

  34. ageLOC Process • Identifying Youth Gene Clusters (YGC’s), and understanding their youthful expression level • Targeting - Cataloging the effect different ingredients have on YGC’s. • Resetting - Developing formulas that reset these YGC’s back to their youthful state, thus restoring the youthful biochemistry of a cell.

  35. SECOND GENERATION AGELOC PRODUCTS

  36. Gene Activity in Skin Cells DNA Microarray Gene Map Over 25000 Genes

  37. For Human Skin: 4 YGCs identified • Cell Turnover • Pigment • Hydration • SkinStructure • AQP3 • POMC 20+ GENES • 35+ GENES 20+ GENES • COL7A1 • IL1B • TIMP1 • IL1B • 60+ GENES • IL6 • SOD2 • PPARG • MT2A • TNFA • TXNRD1

  38. ageLOC Science • Pigment Four YGCs Identified Signs of Aging • Hydration • Fine Lines & Wrinkles Youth Gene Clusters • Cellular Turnover • Youthful SkinStructure • Discoloration • Skin Structure • Skin Tone • Hydration • Texture, Smoothness • Radiance • Pore Size

  39. *Adler, Chang et al. Cell Cycle 2008;7(5):556-559 • Changes in gene activity patterns yield tissue changes as we age • “Interventions can impact gene activity patterns even late in life and may reverse skin aging”*

  40. “THE PROOF IS IN THE PUDDING” • Meaning: The true value or quality of something can only be judged when it's put to use. • “Nu Skin has never developed a product that delivers these kindof results before (both in clinical results and user perception” • Dr. Helen Knaggs, PhD • VP of NuSkin R&D

  41. ageLOC Summary • Nu Skin Enterprises Center for Anti-Aging Research (NSE:CAAR) brings together experts in the field of anti-aging genetics • Only we can Identify Youth Gene Clusters (YGC) • AgeLOC Science Targets the Ultimate Sources of Aging • Only Nu Skin understand how to Reset Youth Gene Clusters to their youthful state • Over the next 10 years as the ageLOC approach matures, its full impact will be realized on many more products - enabling Nu Skin to stay years ahead of our competition

  42. Nutritional Intervention affects age related gene expression and can Reverse Aging Lee et al, Science 1999;285(5432):1390-3; Colman et al, Science 2009;325:201-204

  43. AGELOC OBJECTIVE: LIFESPAN VS. HEALTH or BEAUTY SPAN Health or Beauty Index YEARS

  44. THANK YOU

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