stephen holt md-american naturopathic medical association keynote anti aging trilogy ...

8/8/2019 Stephen Holt MD-American Naturopathic Medical Association Keynote Anti Aging Trilogy Presentation2010

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THE ANTITHE ANTI--AGING TRILOGY:AGING TRILOGY:

STEPHEN HOLT, MD, ChB., DSc, LLD (Hon.), PhD, ND,

FRCP(C) MRCP (UK), FACP, FACG, FACN, FACAM,OSJ, Distinguished Professor of Medicine,

(Scientific Advisor to Natural Clinician, LLC)

CALORIE RESTRICTION AND MIMETIC COMPOUNDS

SUPORTING TELOMERES AND TELOMERASE

STEM CELL TREATMENTS


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THE MOST IMPORTANT AREAS OFTHE MOST IMPORTANT AREAS OF

SCIENCE IN LONGEVITY PROMOTIONSCIENCE IN LONGEVITY PROMOTION There are three innovative areas of medical science

that will drive therapeutic and research interest in the

first quarter of this millennium. These three areas constitute The Anti-Aging Trilogy:

1. The use of calorie restriction or calorie restriction

mimetic compounds

2. The application of techniques to lengthen telomeresand modulate telomerase activity

3. The use stem cell treatments.


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APPLYING CALORIE RESTRICTIONAPPLYING CALORIE RESTRICTION

A large body of medical evidence shows thatrestricting calories of the order of 30-50%

below average free feeding calorie intake

inhibits aging processes in all species tested.

A target of about 40% reduction in average

calorie intake (2,000 kCal/day) is required,

but compliance may be unattainable.

Calorie reduction must occur with nutrient

dense foods. The Roy Walford concept of the

high/low diet (The 120 Year Diet).


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A PIVOTAL PUBLICATION, WALFORD 1986: HIGH/LOWA PIVOTAL PUBLICATION, WALFORD 1986: HIGH/LOW

DIET WITH THE CONCEPT OF UNDERNUTRITIONDIET WITH THE CONCEPT OF UNDERNUTRITION

WITHOUT MALNUTRITIONWITHOUT MALNUTRITION


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OUTCOMES OF CALORIE RESTRICTIONOUTCOMES OF CALORIE RESTRICTION

Reduction in body temperature. Reduction in fat mass, including visceral

adiposity, with increase in muscle mass.

Restoration of hormonal secretions thattend to fall with age, e.g. DHEA and HGH.

Enhanced cognitive function and mood.

Improved ability for physical activity. Stimulation of growth factors eg BDNF


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SUMMARIZING BIOPHYSIOLOGICALSUMMARIZING BIOPHYSIOLOGICAL

EFFECTS OF CALORIE RESTRICTIONEFFECTS OF CALORIE RESTRICTION

Altered enzyme expression in protein

metabolism and synthesis

Apoptosis regulation Modification of actions of chaperone

molecules

Reduction in glycosylation

Reversal of dysglycemia


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SUMMARIZING BIOPHYSIOLOGICALSUMMARIZING BIOPHYSIOLOGICAL

EFFECTS OF CALORIE RESTRICTIONEFFECTS OF CALORIE RESTRICTION

Suppression of inflammatory

responses

Hormetic effects

Inhibition of glycolysis with insulin

sensitizing actions Genetic regulation e.g. Sir2 or

human homologous SIRT1g


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FOR THE SKEPTICFOR THE SKEPTIC

Source: Reproduced from Life Extension Magazine


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CONCEPTS OF CALORIECONCEPTS OF CALORIE

RESTRICTION MIMETICS (CRM)RESTRICTION MIMETICS (CRM)

A CRM is an agent that has the ability to

reproduce one or more of the principal

biological effects of calorie restriction(Weindruch, R, et al. J.Geront, 56, 20-33 2001).

Many CRM of pharmaceutical or natural origin

induce substantially similar bio-physiological

changes that are documented with prolonged

dietary calorie restriction, in many species.


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CRM IN ANTICRM IN ANTI--AGING THERAPEUTICSAGING THERAPEUTICS

Synergistic combinations of natural

substances with Calorie Restriction Mimetic

properties have been identified and

combined for a nutritional approach to

longevity.

Examples of CRM: Metformin, Resveratrol,

Carnosine, Gymnema, Alpha Lipoic Acid,

Cinnamon, Avocado, OPCs (grape seed),

Ellagic Acid, N-Acetyl-Carnitine, Green Tea


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A NATURAL CRM SUPPLEMENT DEVELOPEDA NATURAL CRM SUPPLEMENT DEVELOPED

BY HOLT MD LABS FOR NATURAL CLINICIANBY HOLT MD LABS FOR NATURAL CLINICIAN

Carnosine

Resveratrol

Gymnema

Alpha Lipoic Acid

Cinnamon Avocado

OPCs (grape

seed)

Ellagic Acid N-Acetyl-

Carnitine

Green Tea

THE POWER OF SYNERGY


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A PROTOCOL FOR NUTRITIONA PROTOCOL FOR NUTRITION

AND LONGEVITYAND LONGEVITY Calorie restriction of a tolerable degree

combined with natural calorie restriction

mimetics.

Maintenance of nutrient density by the useof mixed fruit, vegetable and greens powders

containing minerals and full RDI of vitamins

Extra mineral enrichment Obsessional detection and treatment of

Syndrome X (70 million Americans)


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THE SYNDROME X BRIGADETHE SYNDROME X BRIGADE


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TELOMERES AND TELOMERASETELOMERES AND TELOMERASE

Telomeres are DNA caps at the end of chromosomes

that function to prevent aberration or loss of geneticinformation during cell division.

The enzyme telomerase acts to extend telomeres and

reduce their shortening which occurs with repeated cell

division.Telomere length correlates with age and short

telomeres result in cell senescence, and abnormal

chromosome function.

Shortened telomeres interfere with the normal functionof genes, propagate cancer, cause abnormal immune

function, promote chronic disease and they are believed

to be a direct cause of aging in tissues.


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TELOMERESTELOMERES

Source: Reproduced from www.spectracell.com


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TELOMERES AND TELOMERASETELOMERES AND TELOMERASE

Telomerase activity is found preferentiallyin cancer, germ cells and stem cells.

The idea of lengthening telomeres is an

attractive anti-aging intervention.

Lengthening telomeres by inducing

telomerase presents some hypothetical

risks of promoting cancer.

Suppressing telomerase is proposed as

a cancer treatment.


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SAFE TELOMERE SUPPORT OR LENGTHENINGSAFE TELOMERE SUPPORT OR LENGTHENING

Many factors alter telomere length e.g. age,

sedentary lifestyles, chronic inflammation,

oxidative stress, hormonal deficiencies and

abnormal glucose metabolism.

Single agents that may increase the activity of

telomerase have been proposed for use as

dietary supplements to support telomerelength (Astragalus) but safety issues exist.


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SAFE TELOMERE SUPPORT OR LENGTHENING:SAFE TELOMERE SUPPORT OR LENGTHENING:

THE TELOMERE SUPPORT PROTOCOLTHE TELOMERE SUPPORT PROTOCOL

Initial telomere testing Positive lifestyle change

Dietary adjustments

Meticulous disease management e.g. Syndrome Xand Diabetes mellitus

Miscellaneous interventions: reduction of

cardiovascular risk factors, control of

inflammation, exercise programs, hormone

supplementation

Nutrient, botanical and herbal supplements


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NUTRACEUTICAL INTERVENTION FORNUTRACEUTICAL INTERVENTION FOR

TELOMERE LENGTHENINGTELOMERE LENGTHENING

Synergistic safe combinations of the followingagents is optimal: Chinese Ginger Root, Gingko

biloba, N-Acetyl-L-Cystine, vitamins B12, D3, E,

Nicotinamide, and Folic acid

Peer-review medical literature supports the

above nutrient composition and the use of

omega 3 fatty acids from enteric coated fish oil.

Extracts of Astragalus that directly induce

telomerase activity to lengthen telomeres

cannot be considered to be safe.


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Many Stem Cell TypesMany Stem Cell TypesReproduced from SA Biosciences, Pathways, 2009Reproduced from SA Biosciences, Pathways, 2009


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Stem Cell Therapies:Stem Cell Therapies:

Disadvantages and LimitationsDisadvantages and Limitations

Embryonic Stem Cells, Embryonic Germ Cells

and Fetal Tissue Stem Cells pose major ethical

and moral problems which cannot be resolved.

Cord Blood and Placental Stem Cells poseunresolved technical problems, e.g. survival.

Adult Stem Cells remain an imperfect

therapeutic procedure, except bone marrow.

Induced Pluripotent Stem Cells (Yamanaka,

2006) hold promise


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Adult Stem CellsAdult Stem Cells

Adult Stem Cells (ASC) live in niches in

most organs and they can migrate.

They are tethered in niches by adhesion

molecules that determine cell migration

and niche retention. Compounds thatinterfere with adhesion factors may

mobilize ASC.

Most information is known about HumanBone Marrow Adult Stem Cells.


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A Novel and New Stem Cell Strategy inA Novel and New Stem Cell Strategy in

Integrative Medicine Practice: InducedIntegrative Medicine Practice: Induced

Adult Stem Cell Recruitment (IASCR)Adult Stem Cell Recruitment (IASCR) Induced Adult Stem Cell technologies involve

the stimulation of endogenous stem cells to

regenerate or heal diseased or ailing tissues. Many compounds of natural or

pharmaceutical origin may play an active rolein the proliferation of human Adult Stem

Cells or cells carrying markers CD34+ andCD133+ (Jensen GS et al, 2002 and Bickford Pet al, 2006, Holt S, 2008).


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The Concepts of IASCR: Part 1The Concepts of IASCR: Part 1

Mobilize Adult Stem Cells from bonemarrow and other niche locations (?)

Increase circulation of ASC with a

semicontinuous, safe stimulus. Herbs,botanicals and nutrients are preferred to

drug approaches (cost, side effects)

Protect stem cells from oxidative damage Encourage homing to desired target organ


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The Concepts of IASCR: Part 2The Concepts of IASCR: Part 2

Assistance in the differentiation of Adult

Stem Cells to replace cell types of the

diseased organ has to be developed.

A body of research demonstrates that

human bone marrow Adult Stem Cells

are able to home in on diseased organs

and differentiate into many cell types

(Egletis, 1997 and Korbling et al, 2002).


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Factors that Mobilize Stem orFactors that Mobilize Stem or

Progenitor CellsProgenitor Cells

DRUGS (or isolated biologicals in clinical use

or trials): IL1, IL3, IL6, Stem Cell Factor (s),

erythropoetin, G-CSF etc.

NUTRACEUTICALS : oleic acid, linolenic acid,blueberry, blue-green algae (AFA), green tea,

fucoidan and vitamin D3. Putative releasers or

antioxidant protection with fucoxanthin, beetroot, spirulina, spinach, ashwagandha, grape

seed extract. Cofactors Vit B12, Folate


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THE ANTITHE ANTI--AGING TRILOGYAGING TRILOGYStephen Holt MD, 2010Stephen Holt MD, 2010

CALORIE

RESTRICTION

TELOMERES

STEM

CELLS


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CONCLUSIONS: THE ANTICONCLUSIONS: THE ANTI--AGING TRILOGYAGING TRILOGY

Research and the application of technology to

achieve the favorable outcome of calorie restriction,

telomere support and stem cell treatments is

proceeding at a rapid pace. Natural approaches exist.

The Naturopath has a variety of botanicals, herbsand nutrients that have an evidence base to support:

1. Bio-physiological changes that occur with calorie

restriction. Calorie Restriction Mimetics

2. Telomere support Clinical Telomere Support

3. Stem cell mobilization and potential recruitment

stephen holt md-american naturopathic medical association keynote anti aging trilogy ...

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