THE NU SKIN OPPORTUNITY

Richard J. DeAgazioRuby Executive

www.stayyoung.nsedreams.com

THE NU SKIN OPPORTUNITY

The world’s leading anti-aging company is addressing the sources of aging, not just the

signs and symptoms.

TRADITION OF INNOVATION

3

• Nu Skin 180• Galvanic Spa• Scanner• Nano• g3• TruFace essence

ultra

SIGNS

Developing products that address the sources of aging, not just the signs and

symptoms.

What is ageLOC?

D. James Morré, PhDDepartment of Medicinal Chemistry and Molecular Pharmacology

andDorothy M. Morré, PhD

Department of Foods and NutritionPurdue University, West Lafayette, Indiana

ARNOX, AN AGING ENZYME: 1ST AGELOC SOURCE OF AGING

Identified a NOX which increases with age Nicotinamide adenine dinucleotide OXidase, a hydroquinone oxidase

NOX

QuinoneReductase

Q10 Q10H2

1/2 O2 H2O

NAD(P)H + H+

NAD(P)+

ProteinSS

ProteinOutside

Inside

Plas

ma

Mem

bran

e

2 O2 SHSH

2 O2-

arNOX Generates Superoxide O2-

A powerful free-radical generator

GENESIS OF AGELOC

Why Some People Look Years Younger

Than They Really Are.

The arNOX discovery helped explain…

HUMAN GENOME

• Our genome encodes for:– our looks– our size– how our bodies work– our health– our behaviors– Our longevity

Genes impact structure and function of the body

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• 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

After 20 yrs Human Genome Sequenced

The Human Genome consistsof at least 25,000 – 30,000 genes

GATCGACTCCTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCCTTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTGATCGACTCCC---TTCCTGGVGCAGCGTGAATATCGATAGAGATCCCTTCGAGAAAGTAAAGT

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

NSE:CAAR Anti-Aging Genetic Experts

Published over 300 scientific papers, and

their insights have changed the way aging is viewed.

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.

Cellnucleus

DNA (stored on chromosomes)

Genetics 101

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…)

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.

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

To better understand aging, we need to know the expression level for every gene.

arNOX Elastin

…in a single experiment.

Gene Expression Profiling 101

arNOX (0)

Elastin (8)

Collagen (6)

MMP (2)

Microarray (e.g. Gene Chip)Young Skin

Key - High Activity

- Off

- Medium Activity

- Low Activity

Gene 1arNOX

Gene 2Elastin

Gene 3Collagen

Gene 4MMP

Young Skin Fibroblast (Hypothetical)

DNA

mRNA

The expression level for every gene in a single experiment!

arNOX Elastin

Key - High Activity

- Off

- Medium Activity

- Low Activity

DNA Microarray Gene MapOver 25000 Genes

NuSkin ageLOC 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.

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.

Younger Than Chronological Age

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

Gene Expression Profiling 101Gene 1arNOX

Gene 2Elastin

Gene 3Collagen

Gene 4MMP

Young Skin Fibroblast (Hypothetical)

DNA

mRNA

Gene 1arNOX

Gene 2Elastin

Gene 3Collagen

Gene 4MMP

Old Skin Fibroblast (Hypothetical)

DNA

mRNA

Gene Expression Profiling 101Young Skin Old Skin

arNOX (0)

Elastin (8)

Collagen (6)

MMP (2)

arNOX (8)

Elastin (0)

Collagen (2)

MMP (4)

Key - High Activity

- Off

- Medium Activity

- Low Activity

Down regulation Up regulationNo Change

arNOX (+8)

Elastin (-8)

Collagen (-4)

MMP(+2)

Changes with Aging

By comparing the two, you can understand the genetic changes associated with aging

INTELLIGENTBIOINFORMATICS

DATABASE

YOUTH GENE CLUSTERS

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

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.

How Do We Target and Reset YGC’s - Remember the Gene Chip?

Key - High Activity

- Off

- Medium Activity

- Low Activity

DNA Microarray Gene MapOver 20000 Genes

Identifying Changes (Old vs. Young YGC Profile)

Young Skin Old Skin

A B

C D

A B

C D

Key - High Activity

- Off

- Medium Activity

- Low Activity

By comparing the two, you can understand the genetic changes associated with aging

Targeting & Resetting YGC

Young Skin

Old SkinA B

C DA B

C D

Key - High Activity

- Off

- Medium Activity

- Low Activity

Once you map the changes, you can screen for ingredients and formulas that reverse these changes

Post Application

A B

C D

AGING

ageLOC

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.

SECOND GENERATION AGELOC PRODUCTS

Gene Activity in Skin Cells

DNA Microarray Gene Map

Over 25000 Genes

Skin

StructureTIMP1

COL7A1AQP3

IL1B

PPARG

TNFA

POMC

IL1B

IL6

SOD2

MT2A

TXNRD1

60+ GENES

For Human Skin: 4 YGCs identified

Pigment

20+ GENES

Cell Turnover

35+ GENES

Hydration

20+ GENES

Texture, Smoothness

Radiance

Pore Size

Hydration

Discoloration

Skin Tone

Signs of Aging

Fine Lines & Wrinkles

Youthful Skin

Structure

Four YGCs Identified

Youth Gene Clusters

Pigment

Hydration

Cellular Turnover

ageLOC Science

Skin Structure

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”*

*Adler, Chang et al. Cell Cycle 2008;7(5):556-559

“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

1. Nu Skin Enterprises Center for Anti-Aging Research (NSE:CAAR) brings together experts in the field of anti-aging genetics

2. Only we can Identify Youth Gene Clusters (YGC) 3. AgeLOC Science Targets the Ultimate Sources of Aging4. Only Nu Skin understand how to Reset Youth Gene

Clusters to their youthful state5. 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

ageLOC Summary

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

AGELOC OBJECTIVE: LIFESPAN VS. HEALTH or BEAUTY SPAN

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THANK YOU

Richard J. DeAgazio

www.stayyoung.nsedreams.com

rdeagazio@rcn.com

617-413-9777

THANK YOU