Telomeres, aging and prevention. Telomere length decreases with each cell division and can be used as a biomarker for biological aging. While telomerase helps maintain telomere length in embryonic development, it is normally silenced after birth. Cancer cells are able to reactivate telomerase to become immortal. Studies show that increased telomerase through genetic modifications in mice can increase healthspan and longevity while reducing aging effects and slightly increasing cancer risk. Precision medicine approaches using telomere length and other biomarkers may help predict disease risks and develop new prevention and treatment strategies.
Learning and understanding the correlation between telomere shortening and disease is the most important principal to stop the aging process. Dr Sears is one of the worlds most respected and renown Anti-Aging physicians in the world. Please visit our website at www.alsearsmd.com or www.searwellnesscenter.com for tons of great free information.
Dr Una L Fairbrother
Telomere length: a 21st century biomarker" discusses DNA structure and the nature of telomeres. This talk explains the importance of telomere length and the impact of this feature on human health. The talk finishes describing the exciting work being carried out in London Metropolitan University to help develop this measure as a 21st century biomarker.
Analytical performance of a novel next generation sequencing assay for Myeloi...Thermo Fisher Scientific
To support clinical and translational research into precision oncology strategies for myeloid cancers, a next-generation sequencing (NGS) assay was developed to detect common and relevant somatic alterations. To define gene targets that were recurrently altered in myeloid cancers and relevant for clinical and translational research, an extensive survey of investigators at hematology oncology research labs was performed.
Despite the advances in diagnostic methods and techniques for surgical treatment in the last two decades, aortic diseases remain a major cause of mortality and cardiovascular morbidity, challenging physicians and molecular biologists. It is believed that about 600 million years ago, during the Cambrian period, variant forms of life appeared, among them were the oxygen-producing cyano bacteria.
Learning and understanding the correlation between telomere shortening and disease is the most important principal to stop the aging process. Dr Sears is one of the worlds most respected and renown Anti-Aging physicians in the world. Please visit our website at www.alsearsmd.com or www.searwellnesscenter.com for tons of great free information.
Dr Una L Fairbrother
Telomere length: a 21st century biomarker" discusses DNA structure and the nature of telomeres. This talk explains the importance of telomere length and the impact of this feature on human health. The talk finishes describing the exciting work being carried out in London Metropolitan University to help develop this measure as a 21st century biomarker.
Analytical performance of a novel next generation sequencing assay for Myeloi...Thermo Fisher Scientific
To support clinical and translational research into precision oncology strategies for myeloid cancers, a next-generation sequencing (NGS) assay was developed to detect common and relevant somatic alterations. To define gene targets that were recurrently altered in myeloid cancers and relevant for clinical and translational research, an extensive survey of investigators at hematology oncology research labs was performed.
Despite the advances in diagnostic methods and techniques for surgical treatment in the last two decades, aortic diseases remain a major cause of mortality and cardiovascular morbidity, challenging physicians and molecular biologists. It is believed that about 600 million years ago, during the Cambrian period, variant forms of life appeared, among them were the oxygen-producing cyano bacteria.
TA-65 Telomerase Activator - Is it a key to unlocking the longevity puzzle?Ivan Joksimovic
TA-65 is a natural supplement without any active ingredients added. The only way to lengthen telomeres is through the activation of an enzyme called telomerase. Currently the only way to activate telomerase is to take TA-65 supplement. The telomerase-activating potency of TA-65 has been independently proven in rigorous tests by Geron and Sierra Sciences, two biotech companies specializing in telomere biology.
Telomeres are protective pieces of DNA material at the ends of chromosomes. Like the plastic tips on shoelaces, telomeres prevent chromosome ends from fraying and sticking to each other, which would damage genetic information to cause cancer, other diseases or premature ageing.
Evidence clearly shows that people with long telomeres age healthier and live longer.
Every time a cell divides, the telomeres get shorter. After they get too short, the cell no longer can divide and becomes inactive or dies. This process is related with aging and age related diseases.
Without telomeres, the protective caps at the chromosome - the part containing genes essential for life - would get shorter each time a cell divides. Cell division is needed so we can grow new skin, blood, bone and other cells when needed.
The only way to lengthen telomeres is through the activation of an enzyme called telomerase. Currently the only way to activate telomerase is to take TA-65 supplement.
Telomerase is natural enzyme that stabilizes telomere length by adding DNA repeats (TTAGGG) onto the telomeric ends of the chromosomes, thus compensating for the loss of telomeres when cell divide.
Buy TA-65 now for the best price!
http://www.ta65doctor.com/products-page/
www.ta65doctor.com
El 27 de noviembre de 2014, la Fundación Ramón Areces celebró una nueva conferencia del ciclo que organiza sobre 'Envejecimiento, Sociedad y Salud: envejecimiento y enfermedad' en colaboración con el Centro de Estudios del Envejecimiento. En esta ocasión, la investigadora María Blasco, directora del Centro Nacional de Investigaciones Oncológicas (CNIO), habló sobre 'El origen de la enfermedad'.
Telomere Diagnostics in the areas of Stem Cells and Male Infertility | Life L...Life Length
Through Life Length’s new series of webinars we want to take Telomere Analysis Technology to clearly defined fields, in order to explore the benefits that telomere measurement can add to your practice.
In this third edition, we will look into the role that telomere analysis plays in the areas of Stem Cells and Male Infertility.
Alberto Pappo, MD, St. Jude Children’s Hospital, Memphis TN
Presented at the 2010 Texas Adolescent and Young Adult Oncology Conference hosted by Methodist Healthcare-San Antonio. October 2010.
Robert P. Edwards, MD, Chair of OB/GYN/RS, Co-Director of Women's Cancer Program at University of Pittsburgh, offers information about the current state of immunotherapy for recurrent ovarian cancer patients.
Telomere Analysis in the areas of Inflammation, Arthritis and ExerciseLife Length
Through this Life Length´s new series of webinars and educational sessions we want to take Telomere Analysis Technology to clearly defined fields, in order to explore the benefits that telomeres measurement can add to your practice.
In this second edition, the areas of Inflammation, Arthritis and Exercise in combination with the role that telomere analysis plays in them will be covered.
Telomere Analysis in the areas of Diet, Supplements and DiabetesLife Length
Through this Life Length´s new series of webinars and educational sessions we want to take Telomere Analysis Technology to clearly defined fields, in order to explore the benefits that telomeres measurement can add to your practice.
In this first edition, the areas of Diet, Supplements and Diabetes in combination with the role that telomere analysis can play in them will be covered.
LIFE LENGTH CAN HELP YOU BOOST YOUR CELL PRODUCT DEVELOPMENT PROJECTS RELATED TO: CELL LINES SUPPLY, DNA DAMAGE, BIO-PHARMACEUTICAL PRODUCTS FOR CELL THERAPY AND REGENERATIVE MEDICINE AND BASIC RESEARCH
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
Follow us on: Pinterest
Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
11. La medicina de las 4 Ps
•PREDICTIVA
•PREVENTIVA
•PERSONALIZADA
•PARTICIPATORIA
La detección temprana 90%
de supervivencia
La detección tardía 10%
de supervivencia
NEJM Modelo matemático 1980-2000
Reducción de los FRs
Nuevos tratamientos
Solo el 7% debido CABG o STENTs
NEJM enero 2013
12. Progress in science
depends on new techniques,
new discoveries, and new
ideas probably in that order
Sydney Brenner
13. Tecnologías que crecen exponencialmente
Test genéticos a bajo coste
Test de medición de Telomeros
Computadores-Bio-informática, Historia y
archivos electrónicos
Técnicas de imagen TAC, RM (Colonoscopia
virtual), “IPad”
Conexión por Internet, medicina on-line (visitas
virtuales)
Redes Sociales
Mi tecnología favorita es el iPhone “digital medicine”
NUEVAS TECNOLOGÍAS
16. An embryonary gene known as telomerase is able to elongate
telomeres to compensate excessive telomere loss during embryo
development.
This gene, telomerase, is silenced after birth … however …
Cancer cells manage to reactivate telomerase, thus escaping the mortal
fate of adult cells and becoming immortal.
TTAGGG TTAGGG
AATCCC AATCCC
genes telomeres
TTAGGG TTAGGG
AATCCC AATCCC
TTAGGG TTAGGG
AATCCC AATCCC
cell death
cell senescence
aging
TTAGGG TTAGGG
AATCCC AATCCC
genes telomeres
cancer
TTAGGG TTAGGG
AATCCC AATCCC
TTAGGG TTAGGG
AATCCC AATCCC
TTAGGG TTAGGG
AATCCC AATCCC
TTAGGG TTAGGG
AATCCC AATCCC
TTAGGG TTAGGG
AATCCC AATCCC
17. Telomere length as a biomarker of biological age & health status
Canela et al., PNAS (2007)
Telomere length predicts age & cognitive impairmentTelomere length decreases with age
HTQFISH
18. cancer
(> 95% of cancers
activate telomerase)
high
Telomerelength
disease
health
age
Telomeres, telomerase and aging
Human pathologies due to telomerase defects
dysqueratosis congenita (DKC1, Terc)
aplastic anemia (Terc, Tert)
idiophatic pulmonary fibrosis (Terc, Tert)
loss of the regenerative capacity of the skin
lungs, bone marrow…
Telomere length=Biomarker of aging?
Lower percentiles of telomere length=
higher risk of diseases (cardiovascular,
neurodegenerative, death by infections)
22. 0 10 20 30 40 50 60 70
0
5
10
15
20
Meantelomerelength(Kb)
Age (years)
0 10 20 30 40 50 60 70
0
10
20
30
40
50
60
%shorttelomeres(<3kb)
Age (years)
Telomere length measurements for individuals
% short telomeres detect more differences between individuals than average length
% short telomeres show higher dispersion as we age
% short telomeres are likely to reflect “way of living” (environment) or biological age
23. Bioactive food components can influence genetic and epigenetic events
associated with a host of disease processes
Trujillo E et al. J Am Diet Assoc 2006;106:403-413
24. Trujillo E et al. J Am Diet Assoc 2006;106:403-413
Dietary factors and the regulation of DNA methylation “CpG sites” 28 millones
S Horvad clock-watcher Nature April
2014 Nature 508,22:2014
Methylation
status
353 CpG sites
algorithm
25. Genetic tests: genes as risk factors for disease
INHERITED
Telomere tests: indication of the degree of aging
INHERITED ENVIRONMENT
MORE POWERFUL PREDICTIONS
OF RISKS AND TIME OF ONSET
# aging is the highest risk factor for all diseases
# telomere length integrates both inheritance & environmental factors EPIGENETICS
DEVELOPMENT OF
NEW TREATMENTS TO
PREVENT DISEASE
A NEW ERA in medicine?: Personalized & preventive medicine
27. Telomere length and Cancer
The Association of Telomeres length and Cancer: a Meta-analysis
S A Savage et al Cancer Epidemiology Biomarkers Prev 20:1238,2011
Short Telomeres are associated with excess Cancer Incidence and mortality
A L Kamaroff JAMA 2010 july 7 P Willet JAMA 304:69, 2010
Fifteen year follow up of association between Telomere length and
incidence Cancer and Cancer mortality
JAMA 306:42,2011
28. Breast cancer: Familial breast cancer
BRCA1/BRCA2
BRCA1
Age (years)
RelativeTelomerelength
BRCA2
Age (years)
RelativeTelomerelength
-0.5
0
0.5
1
1.5
2
2.5
3
3.5
10 20 30 40 50 60 70 80
BRCAX
Age (years)
RelativeTelomerelength
-0.5
0
0.5
1
1.5
2
2.5
3
3.5
10 20 30 40 50 60 70 80
SporadicBC
Age (years)
RelativeTelomerelength
-0.5
0
0.5
1
1.5
2
2.5
3
3.5
10 20 30 40 50 60 70 80
-0.5
0
0.5
1
1.5
2
2.5
3
3.5
10 20 30 40 50 60 70 80
A C
B D
More powerfull tools to predict risk factors and develop new treatments
Javier Benitez (CNIO)
33. Linear regression:
WT: Slope=-7.03 ± 1.24 kb/year
R2=0.31 (Quadratic: R2=0.34)
p<0.0001
TgTERT: Slope=-7.05 ± 1.60 kb/year
R2=0.22 (Quadratic: R2=0.30)
p<0.0001
0.0 0.5 1.0 1.5 2.0 2.5
0
10
20
30
40
50
60
70
80
Age (years)
Meantelomerelength(kb)
Vera et al., Cell Reports, 2012
Mouse telomeres shorten 100-times faster than human telomeres
Humans: 70 bps/year
Mice: 7 Kb/year
Increaseinthe%of
shorttelomeres(permonth)
The increase in the % of short telomeres predicts individual mouse longevity
0 50 100 150 200
-0.5
0.0
0.5
1.0
1.5
Lifespan (weeks)
WT: Slope=-0.005022 ± 0.002550
R2=0.2
p=0.06
TgTERT: Slope=-0.01267 ± 0.005604
R2=0.3
p=0.04
WT
TgTERT
WT
TgTERT
34. telomerase-deficient
wild-type
Blasco et al., Science (1995)
Blasco et al., Cell (1997)
Lee, Blasco, et al., Nature (1998)
González-Suarez et al., Nat Genet (2000)
González-Suarez et al., EMBO J. (2001)
Flores et al., Science (2005)
Telomerase-deficient mice (Terc-/-):
decreased regenerative capacity
due to stem cell dysfunction
less cancer
Super-telomerase mice (K5-Tert):
better tissue fitness
slightly more cancer
The role of telomerase in chromosome stability, cancer & aging
35. Tomás-Loba et al, Cell (2008)
SUPERWild-type
Defeating aging with increased telomerase + tumor suppression
36. Increased “health span” & longevity in SUPER mice
Cancer-free survivalOverall survival
0
20
40
60
80
100
0 60 80 100 120 140 160 180
Sp53 (n=25)
SUPER (p=0.003; n=6)
survival(%)
age (weeks)
+50%
normales (n=25)
0
20
40
60
80
100
0 60 80 100 120 140 160 180
Sp53 (n=49)
SUPER (p<0.001; n=12)
survival(%)
age (weeks)
+40%
normal (n=49)
0
20
40
60
n=25
n=6
p=0.003
0
20
40
60
n=49
n=12
p<0.001
normal SUPER
Survivalat3years(%)
normal SUPER
Survivalat3years(%)
Tomás-Loba et al., Cell (2008)
Healthspan
37. Improved neuromuscular fitness
25000
30000
35000
40000
45000
glucosetolerance(AUC)
**
30-76 weeks
Glucosetolerance(AUC)
n=5
n=3
wildtype SUPER
p=0.02
Improved glucose tolerance
0
25
50
75
100
125
Successrate(%)
n=11
n=9
wildtype
p=0.02
n=8 n=10
SUPER
p=1
young (5-20 weeks) old (116-160 weeks)
Improved health late in life in SUPER mice
Tomás-Loba et al., Cell (2008)
38. SUPER-Mwildtype
young (5-12 weeks)
old (123-165 weeks)
wildtype
Subcutaneousfatlayer(m)
0
20
40
60
80
100
120
n=19
n=24
SUPER-M
n=11
n=61
Less skin aging in SUPER-M mice
Subcutaneous fat
old (123-165 weeks)
Tomás et al., Cell (2008)
39. Telomere length and ATHEROSCLEROSIS
Critical values of replicative senescence the “hayflic limit” vascular age
Circ Res 2006
Family History of CHD Heart 2008
European Atherosclerosis Reseach Study II J Mol Med July 2008
White cell telomere lenght and risk of premature AMI Atherosclerosis
Thromb Vasc Biol 2003 Lancet 2001 the WOSCOP study Lancet 2007
Tromboembolism
RY Zee… P Ridker Int J of Clinical Chemistry 2009; 406:148
40. Telomere length and preclinical ATHEROSCLEROSIS
Framingham Heart Study Arterioesclerosis Thromb Vac Biol May 2011
ASKLEPIOS STUDY European Heart Journal 2009 Obese man
Heart 2008 Carotid Atherosclerosis Hypertension 2004:43;182
Coronary Artery Disease Arterioesclerosis Thromb Vasc Biol 2004:24, 546
Calcium Score Atherosclerosis 2009
Vascular thrombosis RY Zee ..P Ridker 2013
42. X
LAD
ligation
Aging is not a disease…but there are many aging-associated diseases
preclinical model for cardiovascular disease
Normal heart
Failing heart
Failing heartNormal heart
PET – FDG uptake
Histopathology
AAV9-TERT
AAV9-empty
43. AAV9-TERT treatment protects 20% of the mice from death by infact
Bruno Bernardes de Jesus
Christian Bär
0 10 20 30 40
40
60
80
100
AAV9-empty
AAV9-mTERT:
2x1012vg/m
No virus
Percentsurvival
Heartinfarct
Days after myocardial infarction
n=35
n=37
n=21
p=0,07
74%
57%
FVB/N
0.0
0.5
1.0
1.5
0.0
0.5
1.0
1.5
Longitudinalthickness
(mm)
Transversalthickness
(mm)
1 week
p=0.02 p=0.01
p=0.5
n=4
n=13
n=5 n=4
n=13
n=5
p=0.03 p=0.01
p=0.7
1 week
AAV9-empty
AAV9-mTERT:
2x1012vg/m
Sham (no myocardial infarction)
Echocardiography
44. Myocardial Infaction
AAV9-empty
SHAM
AAV9-mTERT: 2x1012vg/m
An AAV9-TERT treatment reduces scar formation upon infaction
Bruno Bernardes de Jesus
Christian Bär
Masson trichrome
Scar size/LV size, %
Numberofmice
0
5
10
15
20
Mild
Severe
Extremely severe
AAV9-
eGFP
AAV9-
mTERT
0
10
20
30
40
%ofarea
AAV9-
eGFP
AAV9-
mTERT
n=10
n=7
p=0.14
MI
AAV9-empty
AAV9-mTERT:
2x1012vg/m
45. 0
50
100
150
200
meanspotintensity/
nucleus(a.u.)
mean 52.33 a.u.
(1850 nuclei)
mean 64.98 a.u.
(1968 nuclei)
124% of AAV9 empty
p<0.0001
0
50
100
150
meanspotintensity/
nucleus(a.u.)
mean 40.08 a.u.
(2455 nuclei)
mean 44.85 a.u.
(3096 nuclei)
112% of AAV9 empty
p<0.0001
AAV9-empty (n=4)
AAV9-mTERT (n=4)
(2x1012vg/m)
cardiomyocytes fibroblasts (infarct area)
AAV9-TERT treated mice show longer telomeres in heart after infaction
Bruno Bernardes de Jesus
Christian Bär
46. Telomere length and Diabetes
Association of Telomere shortening with IGT and DM2 macroangiopathy
Atherosclerosis Nov 2007
Accelerated senescence in the kidneys of patients with DM2 nephropathy
American J of Physiology 2008 DM2
Microalbuminuria Diabetes Care 2007;30:2909 Diabetologia 2006
Leukocyte Telomere shortening in elderly type 2 DM with previous AMI
Atherosclñerosis 2009
Association of Telomere length with type 2 DM oxidative stress and
UCP2 gene variation Atherosclerosis 2010
DNA damage. Diabetes Care 2006
47. Challenge: Individualized Risk Assessment
in Low- and Intermediate Risk Individuals
Algorithms
Neural
Network
MSCT, MRT, PET
Telomeres
And
Genes of
clinical
relevance
Lp(a) PLA2
CRP, BNP
Apo A-, HDL 2b
ApoB
Phytosterols
Metabolic syndrome
Other
48. CONFIDENTIAL
Rupture-Prone Plaques may not be Severely Stenosed
but are Inflamed with Thin Fibrous Caps
Early Plaque
with Lipid Pool
Thick Cap with Small
Necrotic Lipid Core
“Stable Plaque”
Thin Cap
“Rupture-Prone”
Plaque
Ruptured Plaque
with Thrombus
in Lumen
Adapted from Kolodgie F, et al. Arterioscler Thromb Vasc Biol 2006.
51. Statin may reduce the rate at which Telomeres shorten
Lancet 2001 2007 Jan 13
Omega-3 fatty acid supplementation reduces Telomere shortening in the cognitively
impaired J of Nutrition October 22 2013
Omega-3 fatty acids, oxidative stress and leukocyte Telomere length- A randomized
controlled trial E, Balackburn et al Brain Behavior Immunity Sept 2012
Longitudinal association of Telomere length and Obesity indices in an Intervention Study
with Mediterranean Diet the PREDIMED-NAVARRA trial S Garcia-Calzon International
Journal of Obesity 2014, 38:177
Paula Martínez, Gonzalo Gómez-López, Fernando García, Evi Mercken, Sarah Mitchell,
Juana M. Flores, Rafael de Cabo, Maria A. Blasco. RAP1 Protects from Obesity through
Its Extratelomeric Role Regulating Gene Expression. Cell Reports, 2013; DOI: 1-
Metabolic Syndrome PREVEND study JIM Nov 2013
52. The association between Physical Activity in Leisure time and leukocite Telomere
lenght
LF Cherkas Arch Intern Med 2008;168:154. Lancet oncology Sep 2013
Stress can shorten Telomere in chilhood Nature 17 may2011
Telomere length and Aging related to Depression?
Molecular Psychiatry Nov 12 2013 Biol Psychiatry 2012 ;15:294
53. CORRELATION BETWEEN IMT AND EPC LEVELS IN PATIENTS
WITH METABOLIC SYNDROME
0
1
2
3
4
5
6
7
8
9
0,2 0,4 0,6 0,8 1 1,2
GIM
EPCsTardías(%)CD34+/VE-cadherina+(%)
r = - 0,169
P = 0,017
IMT (mm)