Telomere Analysis in the areas of Diet, Supplements and Diabetes

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Reproduction of this document or any portion thereof without prior written consent is prohibited.
Telomere analysis in the fields
of Diet, Supplements and
Diabetes
April 2018

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New Webinar Series - Telomeres and clinical application in:
1 Diet,
Supplements &
Diabetes
2 Exercise,
Inflammation &
Arthritis
3 Stem Cells &
Fertility
4 Aging

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Telomere analysis in the fields
of Diet, Supplements and
Diabetes
April 2018

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BRIEF HISTORY
After many years of work, Life Length is the
world leader in the field of telomere
diagnostics.
We offer testing services to physicians and
patients, academics, researchers and
corporations across many industries all of
whom are driving the adoption of biomarkers
that can contribute to longer health and
lifespans.
Life Length has developed a unique and
proprietary high-content screen technology.
Our robust, sensitive and reproducible
technology can be combined with other
analyses to provide a comprehensive picture
of a patient’s health.

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TELOMERE BIOLOGY

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Telomeres of a young cell Telomeres of an aging cell
Short telomeres are a contributing factor to
virtually all age-related diseases
WHAT ARE TELOMERES?
TELOMERES ARE THE PROTECTIVE CAPS AT THE END OF CHROMOSOMES WHICH PLAY A VERY
SIGNIFICANT ROLE IN THE AGING PROCESS

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STOP
STOP
STOP
STOP
STOP
STOP
STOP
STOP
HAYFLICK LIMIT
NORMAL CELLS HAVE A LIMITED REPLICATIVE CAPACITY

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Aging and age-related diseases
Telomeres
shorten
Cells
replicate
Individua
l ages
Organs
get older
TELOMERE LENGTH IS ONE OF THE MOST CRITICAL BIOMARKERS
FOR AGING
01
03
02
In any living organism, aging is the result of the
decrease in the number and/or function of cells
Every time cells replicate, telomeres shorten until
they reach a point where the cells can no longer
divide properly
Cells with such short telomeres usually become
senescent or enter apoptosis, and eventually die
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Therefore, telomere length is a crucial biomarker
providing insight into understanding organismal
aging

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TELOMERES ARE WELL ESTABLISHED AS A MAJOR
CONTRIBUTING FACTOR OF AGE-RELATED DISEASES
June, 2016
Julio, 2014

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Cancer
DISEASE LEVEL
ORGAN LEVEL
CELL LEVEL
FertilityStress
Arthritis
CNS
DNA DAMAGE
DNA DAMAGE
Senescence and
apoptosis
WHY SHOULD YOU CARE ABOUT TELOMERES?
SHORT
TELOMERES
CVD
Metabolic
Diseases
Stem Cells

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Telomerelength(Kb)
Age (years)
0 10 20 30 40 50 60 70 80 90 100
n = 835
14
12
10
8
6
4
2
0
Source: Aubert et al., Plos Genetics, 2012
TELOMERE SHORTENING IS HIGHLY
HETEROGENEOUS IN RATE
SHORTER TELOMERES CORRELATE WITH INCREASED AGE

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0
2
4
6
8
10
12
0 20 40 60 80 100 120
HealthProfile
Age (Years)
Typical Health Evolution Optimal Health Evolution
MAXIMIZING HEALTHSPAN

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ENVIRONMENTAL FACTORS
Environmental factors, including individuals’ lifestyle
choices, play an even larger role.
GENETICS
Short telomeres are contributing factor
of virtually all age-related diseases.
Genetics play a partial role in
determining telomere length.
CHANGE LIFESTYLE HABITS.
BUILD A PERSONALIZED PROGRAM FOR EACH PATIENT
RESULTS
RECEIVED
STRATIFY RISK BY
COMPARING RESULTS WITH
PATIENTS’ MEDICAL HISTORY

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ENVIRONMENTAL FACTORS
Environmental factors, including individuals’ lifestyle
choices, play an even larger role.
GENETICS
Short telomeres are contributing factor
of virtually all age-related diseases.
Genetics play a partial role in
determining telomere length.
CHANGE LIFESTYLE HABITS.
BUILD A PERSONALIZED PROGRAM FOR EACH PATIENT
RESULTS
RECEIVED
STRATIFY RISK BY
COMPARING RESULTS WITH
PATIENTS’ MEDICAL HISTORY

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TELOMERE LENGTH IS IMPACTED BY AND/OR CONTRIBUTES TO
Diet Supplements Diabetes

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TELOMERES & DIET
Impacting the aging process through
the food we eat

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MEDITERRANEAN DIET
The British Medical Journey
Mediterranean diet and telomere length health study

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Wine
(in moderation)
Vegetables
(raw, steamed, sautéed)
Fruit
(fresh, unprocessed)
WHAT IS A MEDITERRANEAN DIET
MEDITERRANEAN DIET

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Rich in
potassium
Improve
water
retention
May prevent
hypertension
Proteins of high nutritional level
Valuable source of Omega-3
Relatively low energy intake
MEDITERRANEAN DIET

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• Oleic and linoleic acid → Control of
cholesterol and blood circulation
• High content of calcium → Contributes
to the prevention of osteoporosis
• Avoid salted / fried nuts and eat
unroasted instead
• Improves blood circulation
• Helps to reduce bad cholesterol
• Improves blood sugar levels
• Anti-inflammatory properties
• Try to purchase extra virgin whenever
possible
Dried fruits Olive oil
MEDITERRANEAN DIET

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FOODS THAT INDUCE FASTER AGING
WHEAT
Including whole wheat
• Substances called Advanced Glycation
End Products (AGEs) speed up the aging
process in your body, damaging over
time to your organs, your joints and
skin, due to fostered glycation
processes.
• One of the biggest factors that increase
production of AGEs inside your body is
high blood sugar levels.
• Wheat contains a very unusual type of
carbohydrate (not found in other foods)
called Amylopectin-A, which can spike
your blood sugar higher than even pure
table sugar.
IMPACT OF GLYCATION, INFLAMMATION & OXIDATION OVER AGING RATE
Source: Mike Geary - Certified Nutrition Specialist

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• Scientists have found out that the
fructose in HFCS causes 10x more
formation of AGEs in your body than
glucose. What accelerates glycation.
• That means the HFCS consumed daily in
sweetened drinks, and most other
processed foods, highly contribute to
faster aging in the body
• Corn-based foods also contribute
excessive amounts of omega-6 fatty
acids to your diet, which causes an
imbalance in the omega-3 to omega-6
ratio and leads to inflammation and
oxidation.
CORN-BASED FOOD
High-fructose corn syrup, corn cereal, corn chips, corn
oil

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SUGAR
Sugar, sugary foods, certain starchy foods
• Raising average blood sugar levels and
speeding up the glycation process,
sugar can increase the production of
those age-accelerating compounds
called AGEs in the body.
• Using natural non-caloric sweeteners
instead of sugar will positively impact
aging rates.
• Additionally some starchy foods like
white rice, oatmeal, and white potatoes
can also have significant impacts on
your blood sugar and thereby can
increase formation of AGEs.

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CERTAIN VEGETABLE OILS
Soybean oil, canola oil, corn oil or palm oil
• Present in the majority of processed
foods out there, these oils undergone a
refining process under extremely high
heat and use of chemical solvents such
as hexane.
• Creating an oil in which the present
polyunsaturated fats have undergone a
lot of oxidation.
• These polyunsaturated fats are very
inflammatory inside the body,
producing free radicals, damaging cell´s
membranes, contributing to faster
aging and potential heart diseases.

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TELOMERES & SUPPLEMENTS
Supplementing and the aging process

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VITAMINS AND NUTRITIONAL SUPPLEMENTS
• It has , has the effect of sparing the
reactive oxygen species (ROS)
scavenger glutathione, thus reducing
oxidative stress.
• Supraphysiological doses of vitamin B12
derived from supplements can inhibit
nitric oxide synthase and potentially
reduce inflammation.
VITAMIN B12
• Richards et al. reported a positive
association between the concentration
of vitamin D in serum and telomere
length in peripheral leukocytes in
women.
• The anti-inflammatory and anti-
proliferative properties of vitamins D
limit the turnover of cells, thus
potentially reducing their telomere
length attrition.
VITAMIN D

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• Age-dependent shortening of
telomeres as well as decrease in
telomerase activity in cell cultures can
be slowed down and life span can be
increased by addition of physiological
concentrations of vitamin C or vitamin E
to the culture medium.
• Vitamins C & E may limit oxidative
damage to telomeric DNA that would
otherwise cause shortening of telomere
length.
VITAMIN C & E
• Magnesium is required for catalytic
activity of a wide array of enzymes
including those involved in DNA
replication, DNA repair and RNA
synthesis.
• Magnesium deficiency is also
accompanied by an increase in
oxidative stress, which is one of the
factors that result in telomere attrition.
MAGNESIUM

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• Providing additional zinc in the cell
culture medium increases activity of
telomerase.
• Dietary zinc deficiency is associated
with oxidative damage. Zinc
supplementation also reduces the
incidence of infection, which is
another factor that leads to telomere
attrition by higher turnover of cells.
ZINC
• Association between plasma
concentration of the B vitamin folate
and telomere length has been
reported in men and women.
• Folate plays an important role in the
maintenance of DNA integrity and
DNA methylation, both of which
influence the length of telomeres.
FOLATE

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• Omega-3 fatty acids concentration in
plasma is associated with low pro-
inflammatory markers and high anti-
inflammatory markers.
• As a result, a recent study at Ohio State
University has found that omega-3
supplements protect telomeres from
everyday damage.
OMEGA 3
• Curcumin induces synthesis of the
antioxidant glutathione and inhibits
release of the chemokine interleukin-8
and activation of the nuclear
transcription factor NF-kappa B that
mediates inflammatory response.
• Mice that were fed diets containing
curcumin showed decreased DNA
damage and a trend for longer
telomeres.
CURCUMIN

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SUPPLEMENTS INDEX
NUTRACEUTICAL OR SUPPLEMENTS WHICH PURPORT TO CONTRIBUTE TO
MAINTAINING OR LENGTHENING TELOMERES
1. With Astragalus
2. With Telomerase
3. Vitamin complexes
Supplement Categories
*Deliverable PDF for webinar attendees

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TELOMERES & DIABETES

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IMPORTANCE OF THE CORRELATION BETWEEN DIABETES
AND TELOMERE LENGTH
The increasing prevalence of
type 2 diabetes has a huge
impact on global health.
5M
deaths
directly attributable to diabetes, each
year, which is more than the burden of
HIV/AIDS, tuberculosis and malaria
combined.
Type 2 diabetes has been proven
to be an age-related disease, and
therefore associated with
telomere length.
415M
cases
of diabetes in the world. A large
proportion of which remain undiagnosed.
90%
of diabetes cases in adults worldwide are
Type 2 diabetes.

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IMPORTANCE OF THE CORRELATION BETWEEN DIABETES
AND TELOMERE LENGTH

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Pancreas doesn’t
produce insulin.
Genetic factors
causing
autoimmune
response against
insulin producing
cells.
Environmental
factors, such as
toxins or infections,
might trigger it.
Type 1 Pancreas doesn’t
produce enough
insulin or cells
don’t respond to
insulin.
Genetic factors
increase likelihood
of developing it.
Enviromental
factors, mainly the
diet and lifestyle,
increase risk of
type 2 diabetes.
Type 2 Pancreas doesn’t
secret excess
insuline required
during
pregnancy.
Genetic and
environmental
factors
Gestation
al
MAJOR TYPES OF DIABETES
A patient with diabetes does not make or use insulin well. Hence, this leaves glucose
in the bloodstream, causing a higher than normal blood sugar level.

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GROWING EVIDENCE DEMONSTRATES THAT TYPE 2
DIABETES IS RELATED TO TELOMERE SHORTENING
• www.ncbi.nlm.nih.gov/pubmed/28322101

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A SMALL REVIEW OF PATHOPHYSIOLOGY
Insulin acts in the liver to suppress glucose production, and in the muscle and adipose
tissue to stimulate the uptake of glucose, amino acids and fatty acids.
The amount of insulin released to maintain normal
glucose homeostasis is determined by the prevailing
insulin sensitivity.
When insulin resistance develops in the insulin-
sensitive tissues, feedback to the β-cell ensures that it
increases insulin output to maintain normal glucose
tolerance.
When the β-cell is incapable of increasing insulin output in the
presence of insulin resistance, the result is the development of
elevated glucose levels, initially manifest as impaired glucose
tolerance.
As β-cell dysfunction progresses, further elevations in glycaemia
occur and diabetes is the eventual result.

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Increased trigylceride
content in nonadipose
tissue together with
increased serum
levels of trigylcerides may
play an important role in
augmentation
of oxidative stress.
Elevated cellular
glucose
Promotes
Cellular
oxidative stress
Causes
Cellular injury
and decreased
insulin
sensitivity
Elicits
Deletion of
telomeres
Reactive oxygen species have been shown to target
specifically the GGG triplets in telomeric DNA and result in
increased telomere attrition.
Telomerase deficiency has also
been shown to impair replicative capacity of
pancreatic beta cells resulting in defective
insulin secretion and glucose intolerance.
ASSOCIATION BETWEEN INCREASED OXIDATIVE STRESS IN TYPE 2
DIABETES PATIENTS AND SHORTENED TELOMERES

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HOW TO PREVENT DIABETES TYPE 2
Prevention
tips
Increase
you
physical
activity
Eat healthy
Lose
Weight
Stop
smoking
Drink less
alcohol
Monitor
your
physical
condition
First
symptoms
Sudden
weight
loss
Extreme
tiredness
Blurred
vision
Frequent
urination
Increased
thirst
Increased
hunger

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IF YOU WANT TO KNOW MORE
• Hamel FG (2010) Telomeres and type 2 diabetes. Transl Res 155: 164–165.
• Testa R, Olivieri F, Sirolla C, Spazzafumo L, Rippo MR, et al. (2011) Leukocyte telomere length is associated with complications of type 2 diabetes mellitus. Diabet Med 28:
1388–1394.
• Yang H, Jin X, Kei Lam CW, Yan SK (2011) Oxidative stress and diabetes mellitus. Clin Chem Lab Med 49: 1773–1782.
• Eckers A, Altschmied J, Haendeler J (2012) [Oxidative stress in endothelial cells and in diabetes type 2]. Z Gerontol Geriatr 45: 90–94.
• Wolff SP, Jiang ZY, Hunt JV (1991) Protein glycation and oxidative stress in diabetes mellitus and ageing. Free Radic Biol Med 10: 339–352.
• Sampson MJ, Winterbone MS, Hughes JC, Dozio N, Hughes DA (2006) Monocyte telomere shortening and oxidative DNA damage in type 2 diabetes.Diabetes Care 29: 283–
289.
• Maiese K, Morhan SD, Chong ZZ (2007) Oxidative stress biology and cell injury during type 1 and type 2 diabetes mellitus. Curr Neurovasc Res 4: 63–71.
• Henriksen EJ, Diamond-Stanic MK, Marchionne EM (2011) Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free Radic Biol Med 51: 993–999.
• von Zglinicki T (2000) Role of oxidative stress in telomere length regulation and replicative senescence. Ann N Y Acad Sci 908: 99–110.
• von Zglinicki T (2002) Oxidative stress shortens telomeres. Trends Biochem Sci 27: 339–344.
• Bar-Or D, Thomas GW, Rael LT, Lau EP, Winkler JV (2001) Asp-Ala-His-Lys (DAHK) inhibits copper-induced oxidative DNA double strand breaks and telomere shortening.
Biochem Biophys Res Commun 282: 356–360.
• Kanvah S, Schuster GB (2005) The sacrificial role of easily oxidizable sites in the protection of DNA from damage. Nucleic Acids Res 33: 5133–5138.
• Oikawa S, Kawanishi S (1999) Site-specific DNA damage at GGG sequence by oxidative stress may accelerate telomere shortening. FEBS Lett 453: 365–368.
• Harte AL, da Silva NF, Miller MA, Cappuccio FP, Kelly A, et al. (2012) Telomere length attrition, a marker of biological senescence, is inversely correlated with triglycerides and
cholesterol in South Asian males with type 2 diabetes mellitus. Exp Diabetes Res 2012: 895185.

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THE TELOMERE
PROGRAM

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Includes:
THE TELOMERE PROGRAM
01
03
02
Two TAT® test: The first one should be done before
starting the program, and the second one should be done
1 year later
Complete program for nutrition, exercise and meditation
for one year
Monthly follow ups

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THE TELOMERE PROGRAM
▪ Exercise can contribute to
maintaining telomeres
▪ In general, from 3 to 5 sessions
of moderate exercise per week
may be enough.
▪ Extreme exercise may be
harmful
T0 T1
• Greater adherence to the
Mediterranean diet was
associated with longer telomeres.
• Many foods comprising the
Mediterranean diet are rich in
antioxidants which contribute to
slowing the aging process.
• The rate of telomere shortening is
higher in smokers.
• The dosage of cigarette smoking
is shown to negatively correlate
with telomere length
• Researchers have found that
patients who regularly meditate
have better measures of mental
health, blood pressure, and
biomarkers compared to
individuals who have never
meditated.

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1988 1996 1998 2002 2003 2007 2008 2011
FISH based methods
PCR based methods
Southern Blot based methods
2015
Modified from Vera E, Blasco M.A,. “Beyond average: potential for measurement of short telomeres.” AGING, June 2012, Vol. 4, nº6: 379-392
METHODS FOR MEASURING TELOMERE LENGTH
Validated
TAT®
Improved
HT Q-FISH
HT Q-FISH
TelomappingFlow FISH
Metaphase
Q-FISH
qPCR
STELA
TRF

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THE THREE MOST COMMONLY
AVAILABLE METHODS
Q-PCR
Average
telomere
length
Flow FISH
Average telomere
length
TAT®
Median and average
telomere length
% of short telomeres
Q-PCR Flow FISH TAT®
Scalability ✓  ✓
Total reliability  ✓ ✓
Clinical value   ✓

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Clinical
Utility
Multiple
sample
processing
Single sample
processing
Average telomere length Percentage of short telomeres
Population of cells Population of cellsSingle cells Single cells
Scalability
Flow FISH
Q-PCR
Q-FISH
TAT®
(blood)
METHODS FOR MEASURING TELOMERE LENGTH

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LIFE LENGTH’S TELOMERE ANALYSIS
TECHNOLOGY® (TAT®)
Our test is a blood test that measures the length
of over 100,000 telomeres to reveal a person's
cellular or biological age, the age a person
shares with most people of similar physiology
It is simple for doctors and patients because
fasting and preparation for blood collection is not
required
10 ml of blood is needed (depending on
standard tube sized used)
It is essential to complete an online anonymous
health questionnaire:
(www.lifelength-questionnaire.com)
A detailed Results Report is provided; available in
numerous languages
The physician receives the results of patient
samples in approximately one to three weeks
(depending on country of origin and shipping
time for samples)

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info@lifelength.com
c/ Miguel Ángel, 11-2nd floor
Madrid 28010
www. lifelength.com
FOR FURTHER INFORMATION, PLEASE CONTACT
STEPHEN MATLIN
CHIEF EXECUTIVE OFFICER
1 561 886 6685

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Telomere Analysis in the areas of Diet, Supplements and Diabetes