Date of Birth : Makassar/11 Februari 1957

QUALIFICATIONS:

1969 Sekolah Dasar, Surabaya1972 Sekolah Menengah Pertama, Makassar1975 Sekolah Menengah Atas, Makassar1984 Dokter, Fakultas Kedokteran Unhas, Makassar1992 Ph.D, Hiroshima University, School of Medicine, Japan

MEMBERSHIP:

1. Anggota Ikatan Dokter Indonesia2. Pengurus Majelis Kode Etik Kedokteran Indonesia 20073. Anggota Ikatan Ahli Ilmu Faal Indonesia4. Anggota Indonesia Genome Organization

Curriculum Vitae

Irawan Yusuf

SYSTEM BIOLOGY APPROACH OF AGING PROCESS

Implication for Predictive, Preventive, Personalized and Participatory Medicine

IRAWAN YUSUFDepartment of Physiology

Faculty of Medicine Hasanuddin University

INTRODUCTION

• Aging is a complex process involving defects in various cellular components.

• The latest evidence suggests a unifying mechanism for cellular aging that is relevant to the development of common age-related diseases.

• Biological system approach will help us to understand, predictive and preventive the aging -related diseases.

Oeppen and Vaupel, Science 2002

Life Expectancy Around the World

Changes in Age Structure in Indonesia

YEAR 65+ 80+ Total Population (‘000)

19501960197019801990200020102020203020402050

4.03.43.13.53.84.86.07.29.8

13.216.4

0.30.30.30.30.40.50.71.01.32.13.2

7953895955

120086150341182474212092237711261897282851299412311335

Progress in Theory of AgingYEAR

1952 Evolution theory of aging initiated by Medawar.

1956 Free radical theory of aging proposed by Harman.

1957 Williams extended evolutionary theory of aging by introducing the concept of trade-off.

1959 Szilard begins to quantify the idea of somatic mutations.

1961 Hayflick and Moorehead introduced cell replicated senescence.

1963 Orgel proposed phenomenon of feedback of random mistakes.

1977 Disposal soma theory that bridge the evolutionary and mechanistic theory of aging.

1988 Single mutations theory.

1992 Network concept mechanisms of aging by Kirkwood and Franchechi.

1996 First substantive network theory by Kowald and Kirkwood.

1998 Direct evidence of functional changes at the level of stem cell.

2002 Integration system for the biology of aging.

Future System biology concept of aging.

WHAT IS SYSTEM BIOLOGY?

• As a discipline or field of study in its own right, involving the quantitative analysis of interactions between elements of biological systems.

• As a set of multidisciplinary methodologies, in which the emphasis is placed on cycles of iteration between experimental data collection and computational or mathematical modelling.

• As an integrative approach, offering an alternative to the ‘reductionist’ approach that is seen by many to have dominated the research agenda for years.

• As an organizational phenomenon involving the bringing together, in exceptionally close working partnerships, of scientists from diverse disciplinary backgrounds, particularly the biological, engineering and mathematical sciences.

BASIC BIOLOGY OF AGING

Aging

Stress ResponseInflammation

ProliferativeHomeostasis

Genetics

Metabolism

Tissue Aging

BASIC BIOLOGY OF AGING

Aging

Stress Response

Metabolism

ROS

Inflammation

ChronicStress

ProliferativeHomeostasis

Tissue AgingGenetics

Mitochondria

IGF / Sirtuins

LAG

Epigenetics

Omics

Signaling Chaperones

Comorbidity

Immunosenescence

Cytokines

Endocrine

Bones & cartilage

Cardiovascular

Secretome Stress-Induced Apoptosis

GENOMIC-PROTEOMIC ENVIRONMENT

Genetics Metabolism Cell CycleStress

response InflamationTissue aging

INTERMEDIATE PHENOTYPE

AGING AND AGING RELATED DISEASES

Genomic and Environment Interaction of Aging

Systems Biology of Human Aging - Network Model 2010

Model for Aging Related Diseases

Organ-Specific Blood Proteins Will Make the Blood a Window into Health and Disease

• Perhaps 50 major organs or cell types--each secreting protein blood molecular fingerprint.

• The levels of each protein in a particular blood fingerprint will report the status of that organ. Probably need 10-50 organ-specific proteins per organ.

• Need to quantify 500-2500 blood proteins from a droplet of blood.

• Key point: changes in the levels of organ-specific markers will assess all diseases or environmental challenges for a particular organ

Predictive, Preventive, Personalizedand Participatory Medicine

• Driven by systems approaches to disease and new measurement technologies (nanotechnology) P4 will emerge over the next 10-20 years

SYSTEM BIOLOGY POINT OF VIEW• Current research finding suggests that, as cells age, they tend to

accumulate damage. • The rate at which damage arises is dictated, on the average, by

genetically determined energy investments in cellular maintenance and repair, at levels optimized to take account of evolutionary trade-offs.

• Long-lived organisms make greater investments in cellular maintenance and repair than short-lived organisms, resulting in slower accumulation of damage.

• In order to manage the risk presented by damaged cells, particularly the risk of malignancy, organisms have additionally evolved mechanisms, such as tumor suppressor functions, to deal with damaged cells.

• In conclusion, there is plasticity in the natural regulation of aging rate.

IMPLEMENTING SYSTEM APPROACH

Stress EnvironmentPoor

Nutrition

Inflammation

HealthyLife Style

HealthyNutrition

Anti-Inflammatory

THANK YOU