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Anti-Aging-AgingMEDICAL NEWST H E G L O B A L R E S O U R C E F O R A N T I - A G I N G

18TH ANNUAL WORLD CONGRESSON ANTI-AGING MEDICINE AND BIOMEDICAL TECHNOLOGIES

SPECIAL GUEST:SPECIAL GUEST:Suzanne SomersSuzanne Somers

TELOMERES &TELOMERASEAS NATURAL THERAPEUTIC

TARGETS

ESTROGENMETABOLISMITS RISK ON BREAST CANCER

AND MITIGATING EFFECTS

IN THIS ISSUEWelcome Letter

Immune EnhancementBy Nature

Nutritional and GeneticStrategies for longevity

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18TH ANNUAL WORLD CONGRESSON ANTI-AGING MEDICINE AND BIOMEDICAL TECHNOLOGIES

SPECIAL GUEST:SPECIAL GUEST:Suzanne SomersSuzanne SomersSPECIAL GUEST:SPECIAL GUEST:


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Abstract

Agenomic understanding of

aging is paving the way to iden-

tify interventions that can have

signifi cant impact on the aging process.The polymorphic nature of aging indi-

cates that any anti-aging strategy has

to start with a better understanding of

genes that affect tissue viability.

Our anti-aging approach has always

centered on the foundation of good

macro and micro-nutrition, including

the consumption of plentiful plant-

based antioxidants and phytonutrients.However recent advances, especiallywith the mapping of the human genomeand the subsequent development ofDNA microarrays provide (a) an op-

portunity to explore the mechanisms ofaging and (b) the tools to begin address-ing aging at its most fundamental level.We believe that if we are to widen thegap between chronological and biologi-cal age we must better understand therole of gene expression in aging and howdietary ingredients interact with geneexpression in a positive way.


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vitamins, minerals, and phytonutrientsnot only fight free radicals, but theyexert perhaps even more powerful anti-aging effects through a non-antioxidantrole. Phytonutrients, many of whichare antioxidants, also influence the ex-pression or activity of factors involvedin aging including, for example, sirtuins,

AMPK, NFKB and PGC-1 alpha toname a few.4-6 Thus it is becoming in-creasingly clear that the phytonutrientswe thought were merely antioxidantsare also capable of modulating geneexpression.

Gene Expression Science

It is clear that a nutraceutical ap-proach to anti-aging must take into ac-count the polymorphic nature of aging,and that the crosstalk among multiple

genes plays a more important role thanthe action of a single gene in mediat-ing the survival of an organism. Sincethe development of DNA microarraysthat allow scientists to measure thework output of all of the genes in asingle experiment, it is now possible torapidly explore the differences in theexpression of multiple genes betweentwo or more biological conditions ina single experiment. Our researchand development team at Nu Skinbecame intrigued with the possibility

of measuring the aging process objec-tively at the genetic expression levelafter reading some of the exceptionalwork published by Weindruch, Prollaand colleagues (LifeGen Technologies,LLC) (LGT) wherein a powerful tech-nique of differential expression analysiswas being used to conduct genome-wide searches for consistent changesin gene expression patterns that occurduring the aging process.7, 8

Studies using whole-genome tran-

scriptional profiling typically identifythousands of genes that are changedin expression with age. Since many ofthese age-related changes are not univer-sal, but rather are specific to the geneticbackground of the organism being stud-ied, LGT identified biomarkers of ageacross seven strains of mice (5 monthsvs. 28-30 months old) so that only themost conserved relevant patterns of age-related gene expression markers wereconsidered. Moreover, these analyseswere performed in three tissues (heart,

FIGURE 1: LGT identified biomarkers of age across

seven strains of mice (5 months vs. 28-30 months

old) so that only the most conserved relevant

patterns of age-related gene expression markers

were considered. RTqPCR was used to confirm a

panel of 10-20 genes in each tissue.

Introduction

Aging is not an episodic process;rather, it is the consequence of a con-tinuum of cumulative damage occur-ring at the molecular, cellular and tissuelevels. The rate of aging rests on factors,internal and external, that can eitherpositively or negatively influence the

balance between tissue preservation orrepair, and damage. Attenuation of ag-ing is entirely dependent on mitigatingsuch molecular damage by augmentingprotection and compensatory repairmechanisms or slowing the degen-erative processes. In a practical senseweve all probably witnessed cleardiscrepancies between chronologicaland biological age in certain individu-als. And while it has been proposedthat genetic factors contribute to the

phenomenon of people looking old,or young, for their years, most of usintuitively suspect that there are someenvironmental components over whichwe wield a certain amount of control.Therefore, if we are to widen the gapbetween chronological and biologicalage, we must understand the variousmechanisms involved in aging anddevise effective strategies that turnthese mechanisms in favor of tissueprotection or repair and regeneration.The question we are asking is: what

are the lifestyle factors and nutritionalcomponents that may assist us in takingcontrol of our own aging process sothat we can age healthily and reduceage-related morbidity?

Macro and Micro Nutrition

A major factor in healthy aging

involves what, and how much, we eat.There is ample evidence that poor nu-trition, which includes overeating andpoor nutrient density, is linked with anincreased risk for many degenerativediseases including heart disease, diabe-tes and cancer. It is now also becomingclear that even marginal micronutrientdeficiencies over time lead to acceler-ated aging.1 Deficiencies in severaldifferent micronutrients includingfolic acid, vitamin D and Magnesium

lead to DNA damage and accelerateage-related mitochondrial dysfunction;which in turn leads to further oxidativedamage to DNA, RNA, proteins andmembrane lipids leading to functionaldecline in mitochondria, cells, tissuesand organs. Since multiple studies andextensive government-commissionedsurveys point to the widespread natureof inadequate dietary intakes of fruitsand vegetables (and therefore vitaminsand minerals)2it seems prudent that all

individuals either improve their diets orsupplement their diets with a multi-vitamin mineral supplement to ensurethat there are no shortfalls in essentialnutrients.

Free-radical Biology and Antioxidants

A leading hypothesis of aging is basedon the free radical theory of aging byHarman3who argued that oxygen-free radicals produced during normalcellular respiration cause cumulative

damage to molecules which progres-sively leads to loss of functionality ofthe organism. Since Harmans theo-ries were first proposed, a huge bodyof literature has emerged providingevidence that free radicals and oxida-tive stress are involved in many diseasestates, especially age-related degenera-tive disease. Although oxidative stressmay be a significant factor associatedwith aging, it is clearly not the onlycontributor and recently evidence isemerging to support the concept that


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dysfunction associated with agingyields bioenergetic defects within thecell9 that exert profound effects onphysical and mental vitality. Our goalwas to identify and target functionalgene clusters associated with mito-chondrial aging.

In our attempt to identify these gene

pathways we found that of 20,687gene transcripts measured by the Af-fymetrix Mouse Genome array, 1241were associated with the mitochondriaby pathway ontology (using a geneontology database). After our murinefeeding studies and microarray screen-ing we found that 172 of these geneschanged in expression during aging incerebral cortex tissue. In gastrocnemiustissue 220 genes changed which age.Cs-4 opposed the age-related changesin 52 of these genes (P


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