The Future of Humanity in Hands of Our Inner Clock

Preparing for the Biggest Changes.

Preparados para Afrontar los Cambios mas

Importantes en la Historia del Hombre

Tras la Enfermedad el Enfermo, tras el Enfermo

el Hombre

Human Being behind the Disease

Paris, Bruselas, Afganistan, Ucrania, Rusia, Madrid, Barcelona, hambruna en Somalia Sunami, Siria, USA. Climate ChangeSexual discrimination, Inmigration stormMensajes negativos Si hay sangre vende

Conquistas en los últimos 100 años

Steve Pinker

•La epoca mas pacifica de la historia

Charles Kenny

•La alfabetización ha pasado del 25% al 80% en los últimos 130 años

Population explosión of Internet Users

• BROADCAST 2017 $ 23 BILLIONS

• Global conversation 2020 3 billion New Minds

Source: GSMA, “Touching Lives through Mobile Health: Assessment of the Global Market Opportunity”, February 2012

6%2000

6%2000

66%2020

66%2020

Global Populationbillions 23%23%

3 BILLION

Crecimiento tecnologico exponencial

“infinite computing”Sensors Netwoks

Robotics3· D Printing

Synthetic BiologyDigital medicineNanomaterials

Artificial IntelligenceCNN Deep learning 95 VS 86.6

Hyperloop one

“infinite computing”Sensors Netwoks

Robotics3· D Printing

Synthetic BiologyDigital medicineNanomaterials

Artificial IntelligenceCNN Deep learning 95 VS 86.6

Hyperloop one

Mas tiempo para ser felices

85.9—71.3 %

80.4– 68.4%

Lancet 28.08.2015

FranciscoNuñez Badajoz112 años

20162016

2016

Human Developmen What is life? “Heredity molecule”Erwing Schorodinger 1943 statistical Physics and Quantum Mechanics

Implications of Telomere Maintenance in Aging-Related

Disease Progression

Fundacion Fernandez-Cruz, MadridOctober 26, 2015

Elizabeth Blackburn, PhD

University of California San Francisco

10.000 DNA LESSIONS PER DAYPER CELL

DNA repairLindahlModrichSancar

Validation of role of telomerase in cancer & aging

Blasco et al., Science (1995)Blasco, Lee, et al., Cell (1997)Lee, Blasco, et al., Nature (1998)

González-Suarez et al., Nat Genet (2000)Flores et al., Science (2005)

�Premature loss of regenerative capacity of tissues (stem cell mobilization defects)

�Anticipation of many aging-associated pathologies (skin, gut, bone marrow etc)

�Resistant to cancer in late generations (when telomeres become short)

�Premature loss of regenerative capacity of tissues (stem cell mobilization defects)

�Anticipation of many aging-associated pathologies (skin, gut, bone marrow etc)

�Resistant to cancer in late generations (when telomeres become short)

Terc-/-

mice

Elizabeth Parrish 2015Aaron Traywick 2018

Trujillo E et al. J Am Diet Assoc 2006;106:403-413en Epigentic-clock Genome Biology Octob 2013.Nature 508-168 Aprl 2014

The clock-watcher the chemical clock Steve Horvath

CpG sites28 mill16-353Sites96-99.7%

Global M

ethylation HIST

ON

AS

RestingEndothelial Cell

Thrombin

ActivatedEndothelial Cell

TLR2

ActivatedMacrophage

ActivatedDegranulating

Platelet

RestingPlatelet

RestingSmooth

Muscle Cell

ProliferatingModulated

Smooth Muscle Cell

ReactiveReactiveOxygen SpeciesOxygen Species

Tissue FactorTissue FactorProcoagulantProcoagulant

ProPro --inflammatoryinflammatoryCytokinesCytokines

Lipid mediatorsLipid mediatorsOf inflammationOf inflammation

Pro-inflammatoryMediators

(e.g., CD40L, RANTES, IL-6)

Consequences of EROSIONConsequences of EROSION

Croce K, Libby P. Intertwining of thrombosis and in flammation inCroce K, Libby P. Intertwining of thrombosis and in flammation in atherosclerosis. Curr Opin atherosclerosis. Curr Opin Hematol. 2007;14:55Hematol. 2007;14:55 --6161

PMNNETs

PMNNETs

Paul M Paul M RidkerRidker , MD, MPH, MD, MPHEugene Eugene BraunwaldBraunwald Professor of MedicineProfessor of Medicine

Director, Center for Cardiovascular Disease PreventionDirector, Center for Cardiovascular Disease PreventionBrigham and WomenBrigham and Women ’’s Hospitals Hospital

Harvard Medical School, Boston, MA USAHarvard Medical School, Boston, MA USA

Dr Ridker is listed as a co-inventor on patents held by the Brigham and Women’s Hospital

that relate to the use of inflammatory biomarkers in cardiovascular disease and diabetes.

XXVIII XXVIII LeccionLeccion Memorial 2009Memorial 2009

New Insights into the Biology of Atherosclerosis New Insights into the Biology of Atherosclerosis and Primary Prevention:and Primary Prevention:

Controversy and Consensus in the JUPITER TrialControversy and Consensus in the JUPITER Trial

Can targeted AntiCan targeted Anti--Inflammatory Therapy Inflammatory Therapy Reduce Cardiovascular Risk?Reduce Cardiovascular Risk?

Aspirin / StatinsAspirin / Statins

Direct CRP inhibitorsDirect CRP inhibitors

DMARDs/ MTXDMARDs/ MTX

TNF / ILTNF / IL--6 Inhibitors6 Inhibitors

ILIL--1 receptor antagonism1 receptor antagonism

CIRT MTX 15 VS 20 mg/week CIRT MTX 15 VS 20 mg/week ekek

Leukotriene blockadeLeukotriene blockade

CCR2/CCR5CCR2/CCR5

LpLp --PLA2 inhibitionPLA2 inhibition

spLAspLA inhibitioninhibition

RNAiRNAi / anti/ anti --sensesense

““ CANTOS trialCANTOS trial ”” canakinumabcanakinumab

Immunization strategies 5Immunization strategies 5 --LO LO

May 22 2018May 22 2018

Macrophages the mediatorsof H. Pylori-induced gastric

carcinogenesis

EBioMedicine, 2018 EGFR related to tumorogenesis

TNFR1 as target in Alzheimer’s disease

EGF

LA MEDICINA “DE PRECISIÓN”La cumbre de una revolución

• CARACTERISTICAS PERSONALES

• EL EXPOSOMA Y LA MICROBIOTA

• LA REVOLUCIÓN TECNOLOGICA. EMPODERAMIENTO Y BIG DATA.

• LAS CELULAS MADRES Y LA EDICIÓN DE GENES . TERAP IA G.

• La inmunoterapia con celulas T y CAR,

ACT tumor-infiltrating lynphocytes

• EL AUMENTO DE LA LONGEVIDAD-TRANSHUMANISMO

JudyPerkins

JudyPerkins

Michael YoungNew York

RELOJ INTERNO

Juan CarlosIzpisua La Jolla

Edición de genes

Los cambios son:Dificiles al comienzoConfusos durante su desarrolloBellos al finalALL CHANGE ISHARD AT FIRST, MESSY IN THE MIDDLE AND SO GORGEOUS IN THE END

ARTURO FERNANDEZ-CRUZ