Specific Anti-Aging Factorsfor Naturai Clinicians

Concepts of AgingIt is impossible to define the onset of

"old age," which is the result of manyphysiological and sociobehavioralchanges.'"' While many seek the"fountain of youth," no one has foundit. Aging is a complex process that canbe modified only by multiprongedinterventions.'' Positive lifestyle ispivotal in the promotion of health andwell-being. While one can extol thevirtues and benefits of good lifestylefor health maintenance and longevity,the investment in "behavior changetoday for health tomorrow" is a difficult

by Stephen Holt, MDpathway of intervention. Mental andphysical idleness result in loss of vitality.An important promoter of aging is lackof mind or body activity, resulting in the"disuse syndrome," with its hallmark ofpremature aging.'-^

Many theories of aging have beenproposed, but no single explanationsuffices (Table 1). Despite uncertaintyabout aging theories, modern anti-aging research has identified several keydisorders orprocessesthatpromote tissueaging. These processes include immuneimpairment, sleep deprivation, obesity,adverse lifestyle, genetic programming.

Table 1. Theories and Hypotheses of Aging with Comments about AgePromoters and Putative Age Eradicators^"

HYPOTHESES OF AGING COMMENTS

Free Radical Theories Free radicals cause oxidative damage.Antioxidants of many types are valuable.

Cross-Link Theories Cross linking of sugars or aldehydes andproteins cause major alterations in bodystructure and function; concept of AGEs.

Immunologie Theories Autoimmunity increases with age. Thethymus shrinks, and white cell function orantibody production is often compromised.

Mutation and Error Theories Mistakes in DNA replication or RNA functionresult in aging or age related disease, e.g.,cancer.

In-Built Programs of Tissue Aging A program exists in genetic materialtocontrol a number of cell functions.

Stress Theories Stress is cumulative, and lifestyle-related,nutritional deficiencies enhance body stress.Adaptogenic herbs may be of benefit.

Repair Budget Theories Environmental and lifestyle issues alter theinvestment of an organism in tissue repair.

Miscellaneous Obesity, metabolic syndrome X, anddiabetes mellitus are disorders of prematureaging, sleep deprivation, and restorationof biorhythms are important. Need forcorrection of hormonal deficiencies orderegulation. Altered biochemical functions,e.g., poor methylation. Combat chronicinflammation. Lifestyle change pivotal.

poor nutrition, hormonal deficiencies orderegulation, inflammation, oxidativestress to tissues, deficient methylation,and the formation of glycated proteins(Advanced Glycation End Products, orACEs).'-«

A wide range of natural substanceshad been identified that can providefavorable nutritional or chemicaleffects on several of these commondisorders or processes that acceleratetissue aging.''*'"'^ Modern researchhas identified many natural substanceswith anti-aging properties, but simpleinterventions or single supplements(or drugs) cannot address efficientlythe multifactorial aspects of tissue3gjng.ia,9-i2 j he intricate, biochemicalcascades of events involved in agingrequire a synergistic approach to theformulation of anti-aging substances,specifically dietary supplements.

The objective of this articleis to review and focus on anti-aging interventions using dietarysupplements to induce youth-preservingimprovements in body functionsand structures. This compilation ofinformation will permit the naturalclinician to adopt a synergistic approachto the correction or retardation of tissueaging using evidence-based, dietary-supplement strategies.

Dietary SelectionsThe optimal "anti-aging diet" should

be reduced in simple sugars andsaturated fat, while being supplementedwith omega-3 essential fatty acids(EFA).*'^'* The diet should containmodest amounts of protein of mixedorigin (vegetable, meat, dairy, and fishorigin), high in fiber and dense in vitalnutrients, such as vitamins, minerals,and phytochemicals. Perhaps the mostimportant dietary adjustments involvethe reduction of useless, dietary calories(e.g., simple sugars, saturated fat.

90 TOWNSEND LETTER - JULY 2008

or alcobol)^ and a restoration of thebalance of omega-3 EFA to omega-6EFA intake,"''' The widespread,relative deficiency of omega-3 EFA andimhalance of oniega-6:omega-3 dietaryintake ratios have been implicated inproinflammatory states, increased risksof cancer or cardiovascular disease risk,and tbe general promotion of chronicdisease.'"'^

Omega-3 EFA supplementation isa pivotal step in anti-aging, nutrientsupplementation, but many fish oilsupplements are obsolete. The amountsof active omega-3 EFA (eicosapentanoicacid (EPA] and docosahexanoic acid[DHAD required to achieve diseaseprevention or therapeutic benefit aremuch higher than hitherto supposed,and such amounts cannot beadministered efficiently in regular fishoil liquids or capsules.'^ " The optimumway to supplement omega-3 EFA is inwell-tolerated, absorption-enhanced,pure, concentrated forms that are bestpresented in delayed-release, targeted,enteric-coated, capsule-delivery sys-tems.'^ While omega-3 EFA appear tobe of great importance in supplements,the health benefits of omega-9 EFA isapparent in Mediterranean diets that areoften enriched with olive oi l . ' '

There are many accounts of therole of mineral enrichment in the dietof certain ethnic groups that enjoylongevity." Enhanced mineral intakehas been proposed as one explanationfor the longevity of individuals inOkinawa, Japan and people who live inmountain regions of Pakistan (Hunzas).These observations form the basis of theputative benefit of holistic concoctionsof minerals, trace mineral supplements,coral calcium, and cell salt therapies."While good mineral intake may beimportant, other dietary or lifestylefactors combine to play a role in thepromotion of an extended, healthylifespan."

Oxidative Tissue DamageTissue aging, due to free radical

damage, is widely accepted as atenable theory of aging.'^'^ Reactiveoxygen species are formed duringnormal body metabolism and especiallyduring exercise. Many environmentaltoxins have pro-oxidant effects ontissues. The body has efficient waysof defending against the propensity

to cause tissue damage. Endogenousantioxidants can "mop up' free radicals.These antioxidants include Superoxidedismutase (SOD), glutathione, catatase,selenium, and vitamins A, C, and E... toname a few.'^^"

Multifunctional, natural antioxidantsare ubiquitous in fruit, vegetables,and berries." To provide adequateantioxidant coverage, many physiciansare using vitamin supplements (e.g.,A, B complex, C, D, and E) combinedin complex mixtures of berries,greens, and vegetable powders. Theseblended powders contain a vast arrayof antioxidant phytochemicals andmicronutrients. This complex approachhas started to replace the use ofmuttivitamin supplements in the modernpractice of Integrative Medicine. Thekey to antioxidant supplementation isto attempt to cover all body tissues withan antioxidant blanket of compoundsthat access many tissues (lipophilic

and hydrophilic antioxidants). Thisapproach should use antioxidants withdifferent REDOX potentials, in order tomaximize oxygen radical absorbancecapacity (ORAC).''

Cell membranes are particularlyvulnerable to free radical damage.^^This circumstance demands the use oflipophilic antioxidants such as turmeric,vitamin E (tocopherols), or essentialfatty acids of the omega 3 series(indirect antioxidants). Particularlyvaluable common antioxidants includepycnogenol, luteir\ lycopene, ellagicacid, alpha lipoic acid, co-enzymeQIO, green tea or coffee polyphenols,bioflavanoids, and isoflavones.

Co-enzyme QIO (ubiquinone)is a powerful antioxidant withwell-documented benefits in themanagement of cardiovascular disease(angina, congestive cardiac failure,hypercholesterolemia, etc.).^^ This

Table 2: Botanical Agents That Have Adaptogenic orBiological Response Modifying Effects

These natural substances can be combined in synergistic formulations toconstitute a baseline, natural anti-aging approach."

ADAPTOGEN

Ginseng (Panax, Eleutherococcus).

Ashwagandha {)Mthania somnifera).

Dandelion {Taraxacum offícinale).

ACTIONS

...Panax (Chinese/Korean), Eleutherococcus(Siberian), Panax quinqufolius (American)have variable antioxidant, brain-supporting,cholesterol-lowering, and estrogenicactions.

...Ashwagandha contains alkaloidsand antioxidants that may have anti-inflammatory, cognitive-enhancing,anxiolytic, and aphrodisiac qualities.

...Dandelion extract has diuretic, liver-supporting, anti-cancer, antioxidant, bloodglucose-balancing, and antithromboticproperties. It may inhibit ILG and TNFalpha (anti-inflammatory).

Ganoderma {lucidum, Reishi) Ling Zhi (Reishi) mushrooms haveanticancer, antiangiogenic, DNA-protective, anti-inflammatory effects.

Schisandra {chinensis) Schisandra has anti-stress, anti-inflammatory, energizing, immune-stimulating, and hormone-balancingactions.

Rhodiola {rosea) Rhodiola has anti-stress, memory-boosting, and antidepressant actions

Bacopia (monnieri) Bacopia has anti-stress, brain-supporting.and rejuvenating properties.

Resveratrol (skin of red grapes) Many benefits with adaptogenic effects onapoptosis.

TOWNSEND LETTER - JULY 2008 91

Anti-Aging Factors

antioxidant may play a role in themanagement or prevention of maculardegeneration, prostate or breast cancer,cognitive decline, Parkinson's disease,skin aging, muscle weakness, andchronic fatigue syndromes." Idebenoneis a modified form of CoQlO that mayhave a greater antioxidant action thanCoQIO.

Tissue GlycationGlycation or glycosylation results

from the undesirable combination ofaldehydes, glucose, or fructose withproteins.^"* During cell membranedamage by free radicals, aldehydes,such as malondialdehyde (MDA), arereleased. These aldehydes can crosslink sugars and proteins, causing proteinaggregation with consequential loss ofthe functional and structural integrityof several tissue proteins. The linkingof proteins with sugars or aldehydesinvolves a process of carbonylation."^-"This process of protein linking andaggregation attracts further free radicaldamage, resulting in the formationof advanced glycation end-products(AGEs).«'^'^^" These AGEs makecellular attachments that induce tissuedestruction and the generation ofdisruptive end-products {e.g., nitricoxide or inflammatory mediators,including tumor necrosis factor [TNF]and undesirable interleukins [IL-6]).^

The generation of AGEs can beinterrupted by the use of carnosinethat causes "carnosinylation."* Thischemical reaction is protective againstthe process of carbonylation. Carnosinecan combine with MDA, therebyinhibiting the process of glycation.Glycation results in severe compromiseof tissue structure and function inmany organs. The development ofAGEs in metabolic syndrome X anddiabetes mellitus explains the hallmarkpresence of premature aging in thesedisorders.'''' Glycation is clearly relatedto the development of atherosclerosis,beta amyloid deposition in the brain(typical of Alzheimer's disease), andskin aging.* Furthermore, glycationcan involve cross-linking of sugars oraldehydes with both protein and DNA.This circumstance impairs the normalgenetic functions of

Carnosine and its variants (anserine,homocarnosine, N-acetyl carnosine,and carcinine) contain alanine andhistidine.^ Emerging evidence showsthe benefit of carnosine in a variety ofdisorders or illnesses, including statesof chronic inflammation, rheumatoiddisease, hypertension, vascularthrombosis, peptic ulcération, delayedwound healing, skin aging, radiation-induced tissue damage, cancer, andcataracts,^ Carnosine has shown well-defined, anti-aging properties byextending the lifespan of laboratorymice, and it has been shown to expandthe lifespan of human cell lines grownin tissue cultures (fibroblasts), in severallab experiments.^

Methyl Donation (Methylation)The maintenance of the structural

and functional integrity of several keychemical compounds in the bodyinvolvesthedonation of methyl groups."Examples of vital compounds thatrequire methylation for optimal functioninclude high-density Mpoproteins (HDL),DNA, phospholipids, serotonin, andadrenaline. Without a continuing abilityof the body to methytate many pivotalcompounds, normal tissue functionscannot proceed. A common result ofimpaired methylation is the damagingaccumulation of homocysteine.Homocysteine accumulates as a resultof its lack of conversion to methionine{a methyl donor)."

Elevated levels of homocysteineare found in states of inflammationand associated with several diseases,including cardiovascular disease,dementia, osteoporosis, diabetesmellitus, systemic lupus erythematosis(SLE), and other autoimmunedisorders.^ '̂̂ ^ These circumstancesbenefit from the availability of methyldonors such as S-adenosyl methionine(SAMe) or tri-methyl-glycine (TMG),which are present in popular dietarysupplements."

Deregulation of methylation tends tooccur with age, and exercise increasesthe need for methyl group donation.^ Forthese reasons, aging or over-exercisedtissues may suffer protein and DNAdamage.^ A particular problem occurswith collagen destruction in individualswho over-exercise. In competitiveathletes, tendon, periarticular, andligamentous disruptions result from

compromised or sub-optimal methyldonation.^ Committed or elite athletesmay benefit from methyl-donatingsupplements (TMG and SAMe) toengage in preservation of youthfulmusculoskeletal function,

Hormonal Deficiency or ImbalanceThere is no evidence to support the

naïve notion that hormone deficienciesprovide a comprehensive explanationof the aging process. While specifichormonal deficiency or deregulationcontributes to tissue aging in themature individual, simple hormonereplacements with human growthhormone (HGH), DHEA, melatonin, orsex hormones are not "stand-alone,"anti-aging interventions. That said,hormonal therapies show promisingbenefits for anti-aging when used inthe correct context."^^ The relativedeficiency of several hormones thatoccurs with advancing years is perceivedby some physicians as a simpleopportunity to reverse aging by hormonesupplementation. Other physiciansperceive reductions in certain hormonesas a normal healthy adjustment madeby the aging body. Of course, neitherperspective is completely correct, andthese issues remain debatable amongmedical practitioners.

The administration of HGHhas become very popular in anti-aging medicine, but its use remainscontroversial.'^ While a number ofstudies have shown favorable physicaland physiological outcomes with HGHadministration,'^' recent meta-analysisstudies of HGH treatments fail toshow acceptable safety and efficacy."Proponents of growth hormone usein anti-aging medicine report musclemass increase, gastrointestinal benefits,improved visual acuity, enhancedexercise tolerance, blood pressurereductions, improved libido, promotionof immune function, and enhancedcognitive activity.^' Such benefits areundeniable in anecdotal reports, butthe duration of some of the recordedbenefits of HGH may be limited, andthe consequences of long-term use ofHGH in anti-aging strategies remainuncertain.^^'^^

The observed benefits of growthhormone supplementation must bebalanced against known side effects,which are most often experienced

92 TOWNSEND LETTER - JULY 2008

at high dosages of injected H C H . "Adverse side effects of HCH include softtissue swelling, entrapment neuropathy,diabetogenic tendencies, gynecomastia,fluid retention, acromegalic features,and hepatic enlargement." The risk ofHGH as a promoter of cancer growth isa residual concern." Notable evidenceexists that HGH treatments mayenhance risks of colonie cancer." Claimsthat HGH can actually accelerate tissueaging remain challenged. On balance,it is clear that HGH treatments must becarefully planned and monitored by aknowledgeable physician. The formalprescribing guidelines for HGH use inanti-aging practice remain confusing,but many physicians believe that HGHadministration is indicated when matureadults have documented low bloodlevels of HGH of IGF1.

Natural ways of boosting HGHrelease by applying hormonal ornutritional secretagogues are moreportable than HGH injections in clinicalpractice." The value of amino acidsecretagogues has been questionedin elderly humans.*" The classic way

of enhancing the secretion of HGHinvolves the use of growth hormone-releasing hormones (e.g., GHRP-B),"Other hormonal secretagoguesinclude GHRH analogues, Ghrelin,and ProHGH, with or without GHRHcofactors. Some growth hormone-releasing products are administered byoral capsules or tablets, sublingual ororal sprays, with a variable evidence-base for safety and efficacy.^ Growthhormone-releasing co-factors includeglutamine, combinations of arginine,lysine, and ornithine, L-dopa, or plant-derived "mimetics" (Mucuna pruriens),carnosine, homeopathic preparations,gamma hydroxy butyrate {GABA),yeast extracts, and mixed mineralsupplements.^ The use of growthhormone secretagogues over extendedperiods of time may sometimes result intheir ineffectiveness, as the pituitary orits effector mechanisms become tolerantto initial growth hormone-releasingactions.

De-Hydro-Epi-Androsterone (DHEA)is a hormone that is readily convertedto several sex hormones (estrogen.

Anti-Aging Factors

progesterone, and testosterone)." Thedecline in the endogenous availabilityof DHEA with age is associated withseveral disorders of aging includingchronic inflammation, reductionin IGFl, immune impairments,neu rodegenerative disorders (e.g.,Alzheimer's disease), and risks of deathin the elder ly."" The administrationof DHEA in several of these disordersof aging has been reported to producean overall benefit." Adverse effects ofDHEA administration include severedepression and growth-promotingeffects of DHEA on the prostate andperhaps other organs.""

While the benefits of DHEAsupplementation appear attractive, thissupplement should be administeredunder medical supervision because of itsrelatively narrow benefit/risk profile. Thecombined use of melatonin with DHEAmay have added anti-aging benefits.""Melatonin is a potent antioxidanthormone that may improve menopausal

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symptoms, partially restore agerelateddeclines in thyroid function, exert anti-cancer effects, and help restore thebiorhythm of sleep.^" Recent researchhighlights the potential value of topicalmelatonin in reversing many changesfound in aging skin."'^

The administration of conventionalhormone replacement therapy (HRT) towomen in the transition of menopausecarries more risks than benefits,according to "The Women's HealthInitiative Study" in the US and "TheMillion Women Study" in Europe.̂ *̂ ^^More women are now prescribed so-called "bio-identical hormone therapy(BHRT)," but residual concern exists thatthere are insufficient studies of this formof therapy to make clear conclusionsabout safety and effectiveness. I havetended to reject the term "bio-identical"and substitute the term "bio-similar,"which is a more accurate reflection ofthe circumstance. It is proposed thatthe benefits of BHRT outweigh therisks when hormones are used earlyin the transition of menopause andin the correct ratio of estrogens thatmimic normal estrogenic patterns.'^Furthermore, the data may support thetransdermal administration of "bio-similar" estrogens.'*"

Table 3: Proposed or DocumentedEffects of Calorie Restriction on Body

Structures and Functions^^

Lowering of blood pressureInsulin sensitizationReduction of body temperatureApoptosis regulationDecreased oxidative stressEnhanced brain functionStimulation of growth factorsDiminished death riskImproved tissue repairLowering body weightLowering of blood cholesterolIncreased muscle massAltered hormone profilesIncreased energyAnti-stress actionsModulation of protein metabolism

Adaptogenic Herbs and BotanicalsThe term adaptogen is often used in

a loose manner in alternative medicinejargon. Adaptogens are most specificallydefined as naturally occurring plantsubstances that assist in the adaptationof the body to continuing stress.However, this terminology is restrictive,and many natural substances exist thatcan act as biological response modifiers(BRM) in a favorable way. The termsadaptogen and BRM may be usedinterchangeably to advantage. A largenumber of nutrients or botanical agentshave adaptogenic qualities (Table 2).^"Clearly, a good, balanced nutritionalintake of vitamins and phytochemicals ispivotal in a comprehensive adaptogenicbody

Calorie Restriction or CalorieRestriction "Mimics"

Restriction of calorie intakecombined with the maintenance ofnutrient density of food has powerfulanti-aging benefits in rodents andprobably humans. '̂̂ Experimentalcalorie restriction may improve proteinmetabolism with the eliminationof cross-linked protein productsby downregulation of "chaperonemolecules," with resulting increases inhepatic protein elimination.^'* Calorierestriction has been associated withreductions in blood cholesterol andblood markers of inflammation and withimprovements in glucose tolerance.^-^Many of these benefits may be related toloss of adipose tissue, but the proposedactions of calorie restriction are legion(Table 3).

Several natural compounds anddrugs have been proposed as agentsthat can mimic variably the effects ofcalorie restrictions. These putative,calorie-restriction mimetics includeresveratrol, hydroxycitrate, gymnemaalkaloids, alpha lipoic acid, cinnamon(methylhydroxychalones), indoacetate,metformin, and thiazoMdinediones.^Much interest has focused on the anti-aging benefits of resveratrol. Thesebenefits are potent and versatile.They include regulation of apoptosis,antioxidant actions, anticancer effects,cardiovascular benefits, and specificgene-regulating actions.^"""^ The aginggene in question is SIRTl. This genemodulates tissue aging by inhibiting

"^^ Resveratrol exerts

complex, poorly understood effects onapoptosis regulation, with an ability toupregulate or downregulate cell death.^

Toxicity and Premature AgingThe twentieth century witnessed the

increasing use of synthetic chemicals,and the new millennium is a time toexperience the adverse effects of thesetoxins (toxicants). Toxins are ubiquitousin our environment and the bodytissues of animals and humankind."The association between toxicantexposures derived from food, buildings,or consumer goods and chronic diseaseis becoming increasingly obvious incontemporary medical research.*"

Attempts to avoid or ameliorateexposure to environmental toxinsby lifestyle change, consumptionof organic vegetables, and body-cleansing programs are valuable anti-aging tactics.'*'' Integrative medicinenow stresses the use of non-toxicalternatives to many items that containhealth-damaging toxins. Among theundesirable actions of organic chemicals(toxicants) are the promotion of weightgain, propagation of oxidative stress totissues, direct mutagenic effects, and theexertion of unwanted hormonal actions,e.g., xenoestrogens.^'••"•'''

While not prominent in anti-agingadvice, the avoidance of unnecessaryPharmaceuticals and HRT formenopause appears to be a prudentrecommendation.^^ Adverse side effectsof medications and iatrogenic drugcatastrophes are a major cause of deathand premature disability in the US.Furthermore, the use of conventional5ex hormone replacement therapy,with animal estrogens and syntheticprogestins, appears to have more risksthan benefits In the management ofmenopause.^" The proposed safetyof bioidentical hormone treatmentsremains to be defined, despite therhetoric.^^

Immune FunctionImmune senescence is characterized

by both deficiencies and deregulationof immune function.""^"*^ Much interestin natural medicine has focused on thecorrection of Natural Killer cell function(NK cells), at the expense of consideringneeds to modulate other componentsof the aging immune system. While

94 TOWNSEND LETTER - JULY 2006

immune function involves a complexcascade of bio-physiological events,attempts to enhance or modulateimmunity, using natural medicines,has often focused inappropriately onthe use of single agents of botanical ornutritional origin.

My colleagues and I have testedthe hypothesis that complex immunefunctions are best addressed bysynergistic formulations of multipleherbs, botanicals, and nutrients. Invitro and in vivo comparisons ofdietary supplements with effects onimmune function show that synergisticformulations of substances with knownimmune-modulating effects providemore potent and versatile effectsthan single or limited compositionsof immune-stimulating supplements.This approach is summarized in Table4, which identifies a combination ofnatural substances that are associatedwith specific research. This researchshows profound stimulating effectson NK cell activity and cell-mediatedimmunity with associated actions onimmune, molecular cascades. It isnoteworthy that complex immune-modulating formulations can incorporatebotanicals with antiviral properties (e.g.,Andrographis paniculata) to furtherenhance immune protection." Inbrief, evidence has accumulated thatimprovement in immune function maypromote longevity.*^'*

SleeplessnessSleep deprivation has many adverse,

social, psychological, psychiatric, andphysical consequences/'**Sleeptessnesshas been associated with alterationsin appetite that promote weight gain,the induction of inflammation andchronic stress, together with linkage toseveral chronic diseases." Unobtrusiveconsequences of lack of sleep includemood change, depression, F>oor mentalfunction, and metabolic changes similarto syndrome X.''^''" And an associationexists between abnormalities of sleepand premature death.""

Standard prescription sleeping pillsor over-the-counter hypnotic drugsare common causes of iatrogenicproblems.*'"*^ Natural approaches toinduce restful sleep are to be preferredover pharmaceutical approaches.**Such interventions include lifestyle

change, behavioral modifications, andthe use of synergistic combinationsof herbs and nutrients that are part of"the Sleep Naturally Plan."" Certainherbs with adaptogenic or antioxidantproperties can be selected as naturalways of promoting healthy sleep.*' Thisapproach is a viable alternative to usinghypnotic drugs," which may carryinherent risks of premature death.'"

Anti-Aging Nutraceuticai StrategiesIn view of the many factors that

contribute to aging, a holistic approachto anti-aging is required, with dueconsideration for positive lifestylechange. The challenge in using remediesof natural origin as recuperative factoreinvolves the creation of synergistic,naturai formulations that can beadministered in a convenient, cost-effective format that may result inreasonable patient compliance. Suchformulations should include sufficientranges and amounts of evidence-based,anti-aging agents that can access themultiple aspects of the physiologica!and chemical cascades of aging. Insummary, this combined approachrequires a group of nutraceutical, anti-aging factors that can be administeredin a convenient, weil-toierated protocol(Table 5).

ConclusionA focus on a holistic approach to

anti-aging using positive lifestyle changeand natural medicine is a key initiativein modern health care. Once relegatedto the realms of quackery, remedies ofnatural origin play a major role in thepromotion of longevity. The physiciani nvol ved i n anti-agi ng med ici neshould consider "staged strategies'of intervention starting with the mostnatural and simplistic approach ofhealthy lifestyle recommendations,followed by well-designed andtailored nutritional approaches.Popular hormonal interventions can beexercised in these staged strategies, butphysician supervision must be involvedin interventions that alter endocrineprofiles.

Notes1. Klatz R, Kovarik F, Goldman R.. eds. Advances in

Anti-Aging Medicine. Vol. I. Larchnront. New York:Mary Ann Liebert IrK,; 1996.

2. Evans W, Rosenberg I, Thompson J. Biomarkers: TheW Keys to Prolonging Vitalitv. New York. NY: SimonÄ Schuster; 1992.

Anti-Aging Factors

3. West S, TyburivLombifd D. How fo l ive to be ¡00and Enjoy It! North Babylon, New York: AbbottMcDonrwll-Winchester;1977.

4, Comfort A. The Process of Aging. Signe! Science

5- Walford R. The 120 Year Diet: How to Doutíe YourVilal Years. New York, NY: Sirrwn & Schuster 1986,

6. Rabins P, Lauber L Getting OW Wiihout GettingAn)iiovi. London, UK: Penguin Croup Inc.; 2005,

7. Woodruff-Pak D. The Neuropathy o( Aging. Maiden,MA: Blackwell Publishers Inc.: 1997.

8. Kyriazis M. Anti-Aging Medicines. London, UK:Waikins Publishing; 2005.

9. Smith T. Renpwa/: The Anti-Aging Revolution.Emmaus, PA: Rodale Press lnc.:1998.

10. Hendler S. The Complete Guide to Anti-AgingNutrient5. New York, NY: Simon t, Schuster; 1985,

11. Pesmen C. How A K4in Ages. New York, NY:Ballant i ne Books, a division of Random HouseInc.; 1984,

12. Heineitnan ). Heinerman's incychpedia of Anti-Aging Remedies. Paramus, NJ: Prentice Hall; 1996.

13- Willcox B, Willcox D, Suiuki M. The OkinawaProgram New York, NY: Clarkson Potter; 2001.

14. Atkins R, Buff S. Or Alkins' Age-Defying DietRevolution. New York, NY:St. Martin's Press; 2000.

15. Holt S. Combat Syndrome X, Y and Z Little Falls,New Jersey: Wellness Publishing; 2002.

16. Holt S, Wright JV. Holt FCS. NuttUional Factorsfor Syndrome X. Little Falls, New Jersey: WellnessPublishing; 2003.

17. Holt S. A Primer of Natural Therapeutics, ACertification Program for Dietary SupplémentCounselors iDip.DSC). Linie Falls, New Jersey:Wellness Publishing; 2008-

18. Ames BN. Shigenaga MK. Hagen TM, Oxidants,antioKidants arxl degenerative diseases of aging. Proc,Nati. Acad Sei, USA. 1993; 90; 7915-7922

19. Sohal RS, Sohal BH. Brunk UT. Relationship betweenantioKldant defenses and longevity in differenimammalian species. Mech. Ageir\g Dev. 1990; 53:217-227.

Table 4: Nutritional and BotanicalAgents with an Evidence-Base forUse in Combination to Modulateand Promote Immune Function

CourtMy of Hott MO T*chnologÍM

• Andrographis paniculata• Acanthopanax Senticosa• Green tea

Turmeric• Grape seed extract

ZincVitamin CAshwagandhaOregon grapeShiitake mushroom

• Echinacea purpureaGoldensealGolden threadAloe Vera

• Garlic• Astragalus• Korean ginseng

Coriolus versicolorActive Hexose Correlated •Compound (AHCC)Beta glucan

TOWNSEND LETTER - JULY 2008 9S

Ânti-Âging Factors

20

21

24

25

Halllwell 6. Free Radicals, antioxidanls and humandisease. Curiosily, cause or consequence? lancet.1994;344: 721-724,Wang H, Cao G, Pfiof RL, Total antioxidani capacityof fruits. I. Agr. food. Chem. 1996; 44; 701-705,

22. Harman D., Aging. A theory based on free radical andradiation rhemistry. ;. Ceranto/. 1956:11: 288-300.

23. Gaby AR. Enzyme CoQIO. In Pizzorno ]E, MurrayMT, eds. Textbook of Natufal Medicine. New York:Harcourt, Brace and Co t id ; 1999; 211); 663-670Bnawnlee M, Vlassara H, Cerami A. Noneniymalicglycosylation and the pathogenesis oí diabeticcomplications. Ann. Int. Med. 1984;101; 527-537,Miller AL. Kelly GS. Honrocysteine metabolism;nutritional modulation and impaU on health anddisease. In Pizzomo )E, Murray MT, eds. reKtbooii ofNatural Medicine. New York; Harcourt, Brace and CoLtd; 1999; 2(1); 461-475,

26. Mason ). Miller ), The effects of vitamios Bl 2, B6, andfolate on blood homocysterne levels. Ann. NY. Acad.Sei. 1992; 669; 197-203.

27. KlaU R, Kahn C. Crow Young wilh HCH. New Yofk,NY; HarperCollins; 1997.

28. Homer C. WaJtiftg the Warrior Coddess. LagunaBeach, Califomia: Basic Health Publications Inc.;2005

29. Hau L, Bravata D, Ingram O, Smita N, Roberts B,Gerber A, Hoffman A. Systematic review: the safetyand efficacy of growth hormone in the healthy elderly.Annah of internal Medicine. 2007; 146(2): 104-115.

30. Corpa5 E, Blackman MR, Roberson R, et al. Oralarginine-lysine does not increase growth hormone orinsuliif-like growth factor-t in old men. }. Cemnlol.1993;48;M128-133.Hoffman R. Endocrine aspects of aging. In Advancesin Anti-Aging Medirme, Klatz R, ed. Larchmont, NY:Mary Ann Liebert lnc,;19%; 1: 43*49.

32. Gaby AR. Dehydroeptandrosterone. In Textbook ofNatural Medicine. Pizzorno JE, Murray MT, eds. NewYork, NY; Harcourt, Brace and Co Ltd; 1999;2(1):695-699.

33. Yen, S,C,C,, Morales, A.|., Khorram. O., Replacementof DHEA in aging men and women. Potential remedialeffects. Ann. NY. Acad. Sei. 1995; 774: 128-142.

34. Regelson W. Loria R, Kalimi M.Dehydroepiandrosterone (DHEA) - the "mothersteroid.' I. Immunologie action, Ann. NY Acad. Sei.1994; 719; 553-563.

35. Yu HS, Reiter R), Eds, Melatonin Bioiyniheíis.Physiological Effects and Clinical Applications. BocaRaton, FL; CRC Press: 1993.

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31

Stephen Holt, MD, is a clinician, researcher, andbest-selling author. He is a Knight of Grace of the Holy

Order of St. )ohn and the recipient of many honorsand awards for medical teaching and research. He is ascientific advisor to Natural Clinician LLC, Little Falls,

NJ, a company that sells health care products. Dr. Holtis regarded as a pioneer of Integrative Medicine, and he

is the President of the World Organization of NaturalMedical Practitioners (www.wonmp.us).

Poor nutrition

Table 5: The Author's Recommendations for the Rational Use ofCombination Supplements in Anti-Aging Medical Practice.

A universal, baseline approach to body recuperation involves nutritional corrections andspecific formulations of anti-aging substances.*

Preference for multivitamins combined with minerals in powder blends of fruit, berries,greens, and functional herbs or nutrients

Anti-aging factors to correct pivotalbiochemical imbalance, incorporatingmethyl donation and antioxidants tointerfere with tissue glycation andoxidative stress.Recommendations include putativesecretagogues or HGH "helpers."'

Sleep deprivation

Membrane lipid damage and preventionof chronic disease and inflammation

Immune impairment

Hormonal declines

Combat diseases of premature aging

Carnosine, glutamine, S-Adenosyl Methionine (SAMe), Tri-Methyl-Glycine (TMG),Siberian Ginseng {Eleuthorococcus senticosa). Rhodiola rosea. Ashwagandha(Withania somnífera), dandelion root {Taraxacum officinale), Schisandra chinensis.Ganoderma lucidum, Bacopa monnieri. acetyl-l-carnitine, n-acetyl cysteine, citrusbioflavonoids and aipha lipoic acid with folie acid, vitamin B6 and Bl 2 {Homocysteinerelief)

Initial lifestyle change with combination synergistic formulations of melatonin, 5 HTP,adaptogenic, or sedative herbs

Omega-3 essential fatty acids in enteric-coated fish oil capsules (at least 2g/day of30:20 ratio of EPA/DHA)Cofactors required, e.g., minerals

Use of complex formulations that modulate immune cascades with antiviral activity

Evidence-based GH secretagogues and DHEA

Cardiovascular health promotion; management of obesity, metabolic syndrome X, anddiabetes mellitus; cancer prevention counesy of HOUMD Technologies

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