Telomere Analysis in the areas of Inflammation, Arthritis and Exercise

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Telomere Diagnostics in the
fields of Inflammation, Arthritis
and Exercise
July 2018

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New Webinar Series – Telomere diagnostics and its clinical applications in:
1 Diet, Supplements
& Diabetes
2 Inflammation,
Arthritis & Exercise
3 Stem Cells &
Fertility
4 Aging

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Telomere Diagnostics in the
fields of Inflammation, Arthritis
and Exercise
July 2018

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BRIEF HISTORY
After many years of work, Life Length has
become 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 TO 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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Arthritis Exercise
TELOMERE LENGTH IS IMPACTED BY AND/OR CONTRIBUTES TO
Inflammation

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INFLAMMATION &
TELOMERE LENGTH
Correlation and improvements monitoring

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WHAT IS INFLAMMATION?
CHRONIC
INFLAMMATION
—
It can last for
months or years as a
result of failure to
eliminate the cause,
repeated exposure
to the agent.
INFLAMMATION
—
It is the body’s
natural defense
against damaged
cells, viruses,
bacteria, etc.
It aims to remove
these harmful or
foreign invaders and
heal itself.
Accordingly,
inflammation is not
always bad.
ACCUTE
INFLAMMATION
—
Starts quickly and
generally disappears
in a few days.
THUS
—
Chronic
inflammation is not
part of the body's
natural healing
process.
Becoming root
cause of many
diseases and
accelerating the
aging process in the
average person.

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ASSOCIATED PATHOLOGIES TO CHRONIC INFLAMMATION
Inflammatory cytokines can cause muscle pain
and weakness.
Muscle
Inflammation interferes with the body´s natural
ability to repair bone mass.
Bones
Inflammation compromises the liver and kidneys
resulting in earlier appearance of aging signs.
Skin
Autoimmune reactions in the brain can lead to
depression, autism and Alzheimer´s disease
Brain
Autoimmunity can reduce total thyroid receptor
counts and disrupts thyroid hormone function
Inflammation of the heart, arterial and
venous walls contributes to CVDs
Cardiovascular
Chronic inflammation leads to an
enlarged liver or fatty liver disease.
Liver
Inflammation leads to autoimmune reactions
against the linings of airways.
Lungs
Thyroid

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MAIN FACTORS AFFECTING INFLAMMATION
Stress
Activates the same parts of the brain as
physical pain, leading to an inflammatory
response.
Air Pollution
Encourages inflammation and
contributes to insulin resistance.
Smoking
The immune system
overcompensates for the intake of
these toxins.
High glycemic index foods
Foods with white flour, high-sugar
items, and starchy vegetables.
Overweight
Bulging fat cells send out a distress
signal to your immune system.
An overactive
immune
system results
in the body
being flooded
with defense
cells and
hormones that
damage tissues.

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CHRONIC INFLAMMATION AND TELOMERE LENGTH
INCREASED SYSTEMIC INFLAMMATION IS ASSOCIATED WITH DECREASED LEUKOCYTE TELOMERE LENGTH
In states of inflammation, subsequent increases in oxidative stress
and cellular division lead to accelerated erosion of telomeres.
Cause & Effect
suppression of chronic inflammation in the body in association with
telomere length maintenance and monitoring
Thus…
two essential and correlated elements to improve human healthy
lifespan.
Becomes…
Firstly, focus on
reducing inflammation
in the body to protect
telomere length

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HOW TO REDUCE SYSTEMIC INFLAMMATION
MONITOR
Exercise and
Regular
Movement
Reduce
Oxidative
Stress
Improve
Sleep
Avoid
Inflammatory
Foods
Good
Hydration ESR | CRP | PV
So that the body is able to effectively detox.
Cells also require adequate hydration to
carry out proper functions.
Dairy, wheat, rye and barley, processed corn,
fried foods, refined sugar, red meat, artificial
chemicals and additives.
Manage and release stress properly,
prevent infections, avoid exposure to
toxins in your environment and toxic
ingredients in personal care and cleaning
products.
While sleeping the brain flushes out metabolic
debris and the body is put into a deep healing
state.
Delivering fresh blood to your tissues is essential for lowering
inflammation as it helps to flush away metabolic debris and
provide nutrients to inflamed tissues.

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IF YOU WANT TO KNOW MORE
• L. Lu, PhD, C. Johnman, PhD, L. McGlynn, PhD, D. Mackay, PhD, P. Shiels, PhD and J. Pell, MD. Association between Telomere Length, Inflammation and Cardiovascular Risk.
Institute of Health and Wellbeing, University of Glasgow, United Kingdom, Institute of Cancer Sciences United Kingdom, 2015.
• Diana Jurk, Caroline Wilson, Joao F. Passos, Fiona Oakley, Clara Correia-Melo, Laura Greaves, Gabriele Saretzki. Chronic inflammation induces telomere dysfunction and
accelerates ageing in mice. Institute for Ageing and Health, Newcastle University, NE4 5PL, UK. Fibrosis Laboratory, Liver Group, Institute of Cellular Medicine Newcastle
University, 2014.
• S. Bekaert, T De Meyer, ER Rietzschel. Telomere length and cardiovascular risk factors in a middle‐aged population free of overt cardiovascular disease. Aging cell, 2007
• Yasumichi Arai, Carmen M. Martin-Ruiz, Michiyo Takayama, Yukiko Abe, Toru Takebayashi, Shigeo Koyasu. Inflammation, But Not Telomere Length, Predicts Successful
Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians. Centre for Supercentenarian Research Keio University, Newcastle University Institute for Ageing,
Centre for Preventive Medicine Keio University, Department of Biochemistry Keio University, 2015.
• Chol Shin, Inkyung Baik. Leukocyte Telomere Length is Associated With Serum Vitamin B12 and Homocysteine Levels in Older Adults With the Presence of Systemic
Inflammation. Department of Internal Medicine, Korea University, Ansan Hospital, Department of Foods and Nutrition College of Natural Sciences Kookmin University, 2016.
• Jason Y. Y. Wong, Immaculata De Vivo, Xihong Lin, Shona C. Fang, David C. Christiani. The Relationship between Inflammatory Biomarkers and Telomere Length in an
Occupational Prospective Cohort Study. Harvard School of Public Health, Department of Epidemiology, Boston, Massachusetts, USA; Brigham and Women’s Hospital, Channing
Division of Network Medicine, Boston, Massachusetts, USA; Massachusetts General Hospital, Boston, Massachusetts, USA, 2016.
• S Demissie, D Levy, EJ Benjamin, LA Cupples. Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study. Aging
cell, publications, 2006.
• Vasileios Kordinas, Anastasios Loannidis and Stylianos Chatzipanagiotou. The Telomere/Telomerase System in Chronic Inflammatory Diseases. Cause or Effect?. Third
Department of Internal Medicine and Diabetes Centre, Saint Panteleimon General Hospital, Greece ; Department of Clinical Microbiology and Medical Biopathology, Athens
Medical School, Greece; Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Sparta, Greece, 2016.

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ARTHRITIS &
TELOMERE LENGTH
Correlation and application to
delay early-onset

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WHAT IS ARTHRITIS?
ARTHR ITIS
Articulation/Joint Inflammation
Pain
Stiffness
Swelling
Redness
Decreased
range of
motion
Fatigue
Fever
Loss of
weight

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TYPES OF ARTHRITIS
“Arthritis” is not a single disease; it is an informal way of referring to joint pain or joint disease. There are more than 100
different types of arthritis and related conditions, but the most common are osteoarthritis and rheumatoid arthritis.
• The most common.
• Related with age and/or with
previous injuries.
• Cartilage breaks down.
Osteoarthritis Rheumatoid arthritis
• More common in women.
• Unknown etiology.
• Autoimmune syndrome with tissue
destructive chronic inflammation.

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MAIN FACTORS AFFECTING ARTHRITIS
As it adds unnecessary stress
on joints, particularly on the
knees, hips and spine. The risk to develop many
types of arthritis increases
with age, highlighting the
importance of monitoring
the aging process.
Women are more
likely to develop
rheumatoid
arthritis.
A previously injured
joint is more likely
to develop arthritis.Some types of
arthritis run in
families and genes
play a role too.
EXCESS WEIGHT
AGE
INJURIES
GENDER
FAMILY HISTORY

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ARTHRITIS AND TELOMERE LENGTH
• OA is associated with telomere
shortening, even in mild radiographic
hand OA, and increases with disease
severity.
• The closer to the lesion, the greater the
load of short telomeres.
• Age is an important contributing factor to
poor cartilage repair following injury and
to the development of OA.
• Chronologic age itself may be less
important than genetically determined
factors modified by additional risk factors
ranging from joint alignment to injury, to
activity level, to obesity.
• Increased oxidative stress with aging
reduces chondrocyte survival and the
response to growth factors.
Osteoarthritis (OA) Rheumatoid arthritis (RA)
• RA is associated with reduced lifespan and
shortened telomere length in lymphocytes.
• Peripheral blood T cells have shown age-
inappropriate telomeric erosion. Premature
telomeric loss also affected granulocytes,
suggesting that the hematopoietic stem cell is
the primary target.
• Telomere loss in white blood cells is
accelerated by oxidative stress and
inflammation in vitro.
• Telomere shortening causes chromosomal
instability that may lead to the development of
autoimmune diseases, including RA.
• It is unclear whether telomere shortening is the
cause or the consequence of RA.
• Accelerated telomeric erosion occurs during
the first two decades of life.

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HOW TO BETTER CONTROL ARTHRITIS
Certain foods can help control inflammation, many of them are found in
the so-called Mediterranean diet.
DIET
Having protective effects on chondrocytes and MSCs against oxidative
stress and inflammation-induced cellular senescence and apoptosis.
ANTIOXIDANTS
Helps to improve overall health and fitness level without hurting the joints
and fosters the development of stronger bones.
EXERCISE
Taking a better control of and properly monitoring the aging process is
essential here, as age plays the biggest role in the onset of arthritis.
Strengthen
Bones
Boost the
Immune
System
Control
Inflammation

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• Colmegna I, Diaz-Borjon A, Fujii H, Schaefer L, Goronjy JJ, Weyand CM. Defective proliferative capacity and accelerated telomeric loss of hematopoietic progenitor cells in
rheumatoid arthritis. Arthritis and Rheumatism, 2008;58:990–1000.
• Harbo et al.: The distribution pattern of critically short telomeres in human osteoarthritic knees. Arthritis Research & Therapy, 2012;14:R12.
• Kuszel L, Trzeciak T, Richter M, Czarny-Ratajczak M. Osteoarthritis and telomere shortening, Journal of Applied Genetics, 2015;56:169–176.
• Lee YH, Bae SC. Association between shortened telomere length and rheumatoid arthritis: A meta-analysis. Zeitschrift Fur Rheumatologie, 2018;77(2):160-167.
• Li D, Yuan Q, Wang W. The role of telomeres in musculoskeletal diseases. Journal of International Medical Research, 2012;40:1242–1250.
• Schönland SO, Lopez C, Widmann T, et al. Premature telomeric loss in rheumatoid arthritis is genetically determined and involves both myeloid and lymphoid cell
lineages. Proceedings of the National Academy of Sciences of the United States of America, 2003;100(23):13471-13476.
• Steer SE, Williams FM, Kato B, et al. Reduced telomere length in rheumatoid arthritis is independent of disease activity and duration. Annals of the Rheumatic Disease,
2007;66(4):476–480.
• Toh WS, Brittberg M, Farr J, Foldager CB, Gomoll AH, Hui JH, et al. Cellular senescence in aging and osteoarthritis, Acta Orthopaedica, 2016; 87 (Suppl 363): 6–14.
• Yudoh K, Nguyen T, Nakamura H, Hongo-Masuko K, Kato T, Nishioka K. Potential involvement of oxidative stress in cartilage senescence and development of osteoarthritis:
oxidative stress induces chondrocyte telomere instability and downregulation of chondrocyte function. Arthritis Research & Therapy. 2005;7:R380–R391.
• Zhai G, Aviv A, Hunter DJ, et al. Reduction of leucocyte telomere length in radiographic hand osteoarthritis: a population‐based study. Annals of the Rheumatic Diseases.
2006;65(11):1444-1448.

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EXERCISE &
TELOMERE LENGTH
Impacting the aging process through
physical activity

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EXERCISE CONTRIBUTES TO MAINTAIN TELOMERES
AND MAINTAINING TELOMERES LEADS TO…

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THE IMPORTANCE OF REGULAR PHYSICAL ACTIVITY
• Studies show people who do no exercise have shorter telomeres than those who regularly exercise.
• A research project conducted on 5,823 adults by Brigham Young University in 2017, revealed that regular
physical activity helps to slow down telomere attrition.
• Accordingly, the more physically active an indvidual is the less biological/cellular aging takes place in the body.

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EXERCISE TRIGGERS THE PRODUCTION OF
ANTI-AGING HORMONES
• There are specific exercise programs for healthy aging therapies. An individual can be considered as highly
active by engaging in 30 minutes of jogging per day, in case of women, 40 minutes for men.
• That level of physical activity is the minimum required to maximize heart’s pumping power, grow new muscle,
production of higher skeletal muscle satellite content and trigger the production of key anti-aging hormones
like HGH and DHEA.
• However, extreme exercise may be harmful as it produces free radicals leading to inflammation.

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BIOLOGY OF PHYSICAL ACTIVITY AND TELOMERE PROTECTION
Telomeric repeat-binding factor 2
TRF2
ABBREVIATIONS
Reactive oxygen species
ROS
White blood cell
WBC
Haematopoietic stem cell
HSC
Interleukin
IL
Tumor necrosis factor-α
TNF-α
Physical activity and telomere length: Impact of aging and
potential mechanisms of action.
Nicole C. Arsenis, Tongjian You, Elisa F. Ogawa, Grant M.
Tinsley and Li Zuo
Oncotarget, Advance Publications 2017
SOURCE

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TELOMERE TEST AS A CALL TO ACTION FOR LIFESTYLE CHANGES
AND HEALTH THERAPIES ADOPTION
Some days it is hard to find motivation….
…other days motivation finds you
Analyzing your telomere length annually helps
to monitor the improvements achieved in your cellular health.
PREVENTIVE
HEALTHCARE
—
The right actions,
changes and
treatments when it
matters the most

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• Nicole C. Arsenis, Tongjian You, Elisa F. Ogawa, Grant M. Tinsley and Li Zuo. Physical activity and telomere length: Impact of aging and potential mechanisms of action.
Department of Nursing & Department of Exercise and Health Sciences, College of Nursing and Health Sciences, University of Massachusetts Boston, Boston, USA; Department of
Kinesiology & Sport Management, Texas Tech University, Lubbock, TX, USA, 2017.
• Larry A. Tucker. Physical activity and telomere length in U.S. men and women: An NHANES investigation. Department of Exercise Sciences, 237 SFH, Brigham Young University,
Provo, UT 84602, USA, 2017.
• ELISA F. OGAWA, SUZANNE G. LEVEILLE, JULIE A. WRIGHT, LING SHI, SARAH M. CAMHI and TONGJIAN YOU. Physical Activity Domains/Recommendations and Leukocyte
Telomere Length in U.S. Adults. Department of Exercise and Health Sciences, University of Massachusetts Boston, ; Department of Nursing, College of Nursing and Health
Sciences, University of Massachusetts Boston; Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston USA, 2017.
• Flora Y. L. To-Miles and Catherine L. Backman. What telomeres say about activity and health: A rapid review. Flora To-Miles, T325-2211 Wesbrook Mall, University of British
Columbia Vancouver, BC, Canada, 2016.
• Joshua Denham, Christopher P. Nelson, Brendan J. O’Brien, Scott A. Nankervis, Matthew Denniff, Jack T. Harvey, Francine Z. Marques, Veryan Codd. Longer leukocyte
Telomeres Are Associated with Ultra-Endurance Exercise Independent of Cardiovascular Risk Factors. School of Health Sciences, University of Ballarat, Australia, Department of
Cardiovascular Sciences, University of Leicester and National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester,
United Kingdom, 2013.
• Aladdin H. Shadyab, Michael J. LaMonte, Charles Kooperberg, Alexander P. Reiner, Cara L. Carty, Todd M. Manini. Leisure-time physical activity and leukocyte telomere length
among older women. Division of Epidemiology, Family Medicine and Public Health, University of California, San Diego School of Medicine, CA USA; Department of Epidemiology
and Environmental Health, University at Buffalo, NY, USA.; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA, 2017.
• PAUL D. LOPRINZI, JEREMY P. LOENNEKE and ELIZABETH H. BLACKBURN. Movement-Based Behaviors and Leukocyte Telomere Length among US Adults. Center for Health
Behavior Research, Department of Health, Exercise Science, and Recreation Management, University of Mississippi; Kevser Ermin Applied Physiology Laboratory, 2015.

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THE TELOMERE
PROGRAM

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Including:
RECOMMENDED 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 one year later.
Complete program for nutrition, exercise, stress
management and health therapies for one year.
Monthly follow ups on the implemented lifestyle
changes and therapies to encourage compliance.

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RECOMMENDED 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).

46
info@lifelength.com
C/Miguel Ángel, 11-2nd floor
Madrid 28010
www. lifelength.com
FOR FURTHER INFORMATION, PLEASE CONTACT
DR. LISSETTE OTERO
CHIEF MEDICAL OFFICER
+1 561 886 6685
+34 91 737 1298

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