1. Date of Birth : Makassar/11 Februari 1957QUALIFICATIONS: 1969Sekolah Dasar, Surabaya 1972Sekolah Menengah Pertama, Makassar 1975Sekolah Menengah Atas, Makassar 1984Dokter, Fakultas Kedokteran Unhas, Makassar 1992Ph.D, Hiroshima University, School of Medicine, Japan MEMBERSHIP: 1. Anggota Ikatan Dokter Indonesia 2. Pengurus Majelis Kode Etik Kedokteran Indonesia 2007 3. Anggota Ikatan Ahli Ilmu Faal Indonesia 4. Anggota Indonesia Genome Organization Curriculum Vitae Irawan Yusuf

2. SYSTEM BIOLOGY APPROACH OF AGING PROCESS Implication for Predictive, Preventive, Personalized and Participatory Medicine IRAWAN YUSUF Department of Physiology Faculty of Medicine Hasanuddin University

3. 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.

4. Oeppen and Vaupel, Science 2002 Life Expectancy Around the World

5. Changes in Age Structure in Indonesia YEAR65+80+Total Population (000) 1950 1960 1970 1980 1990 2000 2010 2020 2030 2040 2050 4.0 3.4 3.1 3.5 3.8 4.8 6.0 7.2 9.8 13.2 16.4 0.3 0.4 0.5 0.7 1.0 1.3 2.1 3.2 79538 95955 120086 150341 182474 212092 237711 261897 282851 299412 311335

6. Progress in Theory of Aging YEAR 1952Evolution theory of aging initiated by Medawar. 1956Free radical theory of aging proposed by Harman. 1957Williams extended evolutionary theory of aging by introducing the concept of trade-off. 1959Szilard begins to quantify the idea of somatic mutations. 1961Hayflick and Moorehead introduced cell replicated senescence. 1963Orgel proposed phenomenon of feedback of random mistakes. 1977Disposal soma theory that bridge the evolutionary and mechanistic theory of aging. 1988Single mutations theory. 1992Network concept mechanisms of aging by Kirkwood and Franchechi. 1996First substantive network theory by Kowald and Kirkwood. 1998Direct evidence of functional changes at the level of stem cell. 2002Integration system for the biology of aging. FutureSystem biology concept of aging.

7. 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.

8. BASIC BIOLOGY OF AGING Aging Stress Response Inflammation Proliferative Homeostasis Genetics Metabolism Tissue Aging

9. BASIC BIOLOGY OF AGING Aging Stress Response Metabolism ROS Inflammation Chronic Stress Proliferative Homeostasis Tissue Aging Genetics Mitochondria IGF / Sirtuins LAG Epigenetics Omics SignalingChaperones Comorbidity Immunosenescence Cytokines Endocrine Bones & cartilage Cardiovascular Secretome Stress-Induced Apoptosis

10. GENOMIC-PROTEOMICENVIRONMENT Genetics Metabolism Cell Cycle Stress response Inflamation Tissue aging INTERMEDIATE PHENOTYPE AGING AND AGING RELATED DISEASES Genomic and Environment Interaction of Aging

11. Systems Biology of Human Aging - Network Model 2010

15. Model for Aging Related Diseases

16. 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

19. Predictive, Preventive, Personalized and Participatory Medicine Driven by systems approaches to disease and new measurement technologies (nanotechnology) P4 will emerge over the next 10-20 years

24. 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.

25. IMPLEMENTING SYSTEM APPROACH Stress Environment Poor Nutrition Inflammation Healthy Life Style Healthy Nutrition Anti- Inflammatory

26. THANK YOU