THE ANTI-AGING TRILOGY:

•CALORIE RESTRICTION AND MIMETIC COMPOUNDS

•SUPORTING TELOMERES AND TELOMERASE
•STEM CELL TREATMENTS

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)
 THE MOST IMPORTANT AREAS OF
SCIENCE 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 telomeres
and modulate telomerase activity
3. The use stem cell treatments.
APPLYING CALORIE RESTRICTION
• A large body of medical evidence shows that
restricting 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).
A PIVOTAL PUBLICATION, WALFORD 1986: HIGH/LOW
DIET WITH THE CONCEPT OF “UNDERNUTRITION
WITHOUT MALNUTRITION”
 OUTCOMES OF CALORIE RESTRICTION
• Favorable effects on CVS: reductions in heart rate,
blood pressure, LDL cholesterol and triglycerides
(Amelioration of Metabolic Syndrome X).
• Promotion of insulin sensitivity with improvements
in glucose tolerance (normalization blood glucose).
• Increase in protein synthesis with enhanced
elimination of abnormal proteins
• Modulation of apoptosis with DNA support.
• Reduction of oxidative stress.
 OUTCOMES OF CALORIE RESTRICTION
• Reduction in body temperature.
• Reduction in fat mass, including visceral
adiposity, with increase in muscle mass.
• Restoration of hormonal secretions that
tend 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
 SUMMARIZING BIOPHYSIOLOGICAL
EFFECTS 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
SUMMARIZING BIOPHYSIOLOGICAL
EFFECTS 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
 FOR THE SKEPTIC

Source: Reproduced from Life Extension Magazine

 CONCEPTS OF CALORIE
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.
 CRM IN ANTI-AGING 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

•
A NATURAL CRM SUPPLEMENT DEVELOPED
BY HOLT MD LABS FOR NATURAL CLINICIAN

THE POWER OF SYNERGY

 A PROTOCOL FOR NUTRITION
AND LONGEVITY
• Calorie restriction of a tolerable degree
combined with natural calorie restriction
mimetics.
• Maintenance of nutrient density by the use
of 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)
THE SYNDROME X BRIGADE
TELOMERES AND TELOMERASE
•Telomeres are DNA caps at the end of chromosomes
that function to prevent aberration or loss of genetic
information 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 function
of genes, propagate cancer, cause abnormal immune
function, promote chronic disease and they are believed
to be a direct cause of aging in tissues.
 TELOMERES

Source: Reproduced from www.spectracell.com

 TELOMERES AND TELOMERASE
•Telomerase activity is found
preferentially in 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.
SAFE 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 telomere
length (Astragalus) but safety issues exist.
SAFE TELOMERE SUPPORT OR LENGTHENING:
THE TELOMERE SUPPORT PROTOCOL
• Initial telomere testing
• Positive lifestyle change
• Dietary adjustments
• Meticulous disease management e.g. Syndrome X
and Diabetes mellitus
• Miscellaneous interventions: reduction of
cardiovascular risk factors, control of inflammation,
exercise programs, hormone supplementation
• Nutrient, botanical and herbal supplements
 NUTRACEUTICAL INTERVENTION FOR
TELOMERE LENGTHENING
• Synergistic safe combinations of the following agents 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.
 Many Stem Cell Types
Reproduced from SA Biosciences, Pathways, 2009
 Stem Cell Therapies:
Disadvantages 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 pose
unresolved technical problems, e.g. survival.
• Adult Stem Cells remain an imperfect
therapeutic procedure, except bone marrow.
• Induced Pluripotent Stem Cells (Yamanaka,
2006) hold promise
 Adult 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 that
interfere with adhesion factors may
mobilize ASC.
• Most information is known about Human
Bone Marrow Adult Stem Cells.
 A Novel and New Stem Cell Strategy in
Integrative Medicine Practice: Induced
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
role in the proliferation of human Adult Stem
Cells or cells carrying markers CD34+ and
CD133+ (Jensen GS et al, 2002 and Bickford P
et al, 2006, Holt S, 2008).
 The Concepts of IASCR: Part 1
• Mobilize Adult Stem Cells from bone
marrow 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
The 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).
 Factors that Mobilize Stem or
Progenitor 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,
beet root, spirulina, spinach, ashwagandha,
grape seed extract. Cofactors Vit B12, Folate
 In Vivo Release of ASC
(Data from Stemtech Inc. on AFA)

AFA increases CD34+ Stem Cells cf placebo

 THE ANTI-AGING TRILOGY
Stephen Holt MD, 2010

CALORIE TELOMERES
RESTRICTION

STEM
CELLS
CONCLUSIONS: THE ANTI-AGING 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, herbs
and 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