Advancements in Aging Research: Biomarkers & Precision Medicine

1. tion Education Dr. Miswar Fattah, Makassar, 6th June 1978 MSi 1997 2002 2006 : SMAK Depkes Makassar : Chemistry - UNHAS :Master of Sciencein ClinicalChemistry, Biomedicine-UNHAS : Doctor of Medicine - UNHAS 2012 n Current positio 1. 2. 3. 4. 5. 6. 7. Specialty & Research Laboratory Manager, Prodia Clinical Laboratory 2018- Now HKKI: Reference Interval & Decision limit, Indonesian Association for Clinical Chemistry PATELKI : Vice President 2017-Now & Member of Collegium PATELKI 2015 - Now President of ASEAN Association of Clinical Laboratory Scientist (AACLS) 2018-2020 2013- Now Member of Board of Directors of Asian Association of Medical Laboratory Science (AAMLS) 2017 - Now Corresponding Member Scientific Committee Asia Pacific Federation for Clinical Chemistry (APFCB) 2010 – Now Corresponding Member Task Force Young Scientist International Federation for Clinical Chemistry (IFCC) 2016 – Now

2. WHAT NEW & TREND IN AGING RESEARCH FK UNISSULA Semarang, 18 September 2018 Dr. Miswar Fattah, MSi Specialty&ResearchLaboratoryManager ProdiaClinicalLaboratory Miswar.fattah@prodia.com

3. 11 BIG TREND LAB MED • • • • • • • • • • • Balance Centralize Lab and Periphery Lab More Specialize & Unique Test Shift to the multiplex Test More Simple Technology & Fast Results Less Sample / mini sample High Personalize Test Increase coverage of Government insurance High IT utilization (Big Data, IoT & AI) More Preventive test Increase DCT Shifting from Volume Base to Value Base for lab test

4. ANALOGY OF MULTI-LAYER GOOGLE MAPS AND UNDERSTANDING OF PATIENT INFORMATION THROUGH “PATIENT COMMONS” https://newsroom.fmcna.com/whitepapers/personalized-nephrology

5. NEXT GENERATION LABORATORY TO SUPPORT FASTER & ACCURATE CLINICAL DECISION

7. PERAN BIOMARKER DALAM PENELIT IAN KLINIS Cost BIOMARKER Feasibility Study

8. 51– 60 years: aging persons 100 years and over: long-lived persons 61– 75 years: elderly persons The World Health Organization terminology for the aging process 91– 100 years: very old persons 76– 90 years: aged persons

9. Physical Capability Endocrine Function Cognitive Function Biomarkers of Healthy Aging Physiological Function Immune Function

10. BIOMARKERS OF HEALTHY AGING

11. HALLMARK OF AGING

12. E r Long LONGEVITY AS A ALL-IN-ONE PRECISION MEDICINE PLATFORM DO YOU BELIEVE YOU CAN LIVE 120 YEARS? terly is a Personal Longevity Assistant backed by gerontology research that makes personalized ecommendations to help people live healthier and longer lives. Eterly is the first scientifically backed evity Mobile App with a Blockchain backend.

13. LONGEVITY AS A ALL-IN-ONE PRECISION MEDICINE PLATFORM DO YOU BELIEVE YOU CAN LIVE 120 YEARS?

14. • • Chronological age (CA) is a commonly used indicator for aging Chronological Age CA is not an optimal aging progress indicator for the • • • Measure an individual’s accumulation level of damage Track the trajectory of damage over time Differentorgans may ageat different rates Biological Age

15. Telomere Biological age markers Combine biomarkers Physical & Fluid T-cell DNA rearrangement DNA methylation CpGs located in genes ITGA2B, ASPA, and PDE4C

16. A TRUE BIOMARKER OF AGING Predict a person’s physiological, cognitive, and physical function in an age- related way Predict the future onset of age-related conditions and diseases Independently of chronological age Must be testable and not harmful to test subjects It must also be technically simple the test accurately and reproducibly

17. WHAT'S NEW TREND IN GLOBAL RESEARCH • • New Standard & Guideline for the Interpretation of Sequence Variant Precision Medicine Research for all disease • Cancer, Pregnancy genomic, Diagnostic rare disease, pharmocogenomics, Diabetes, Hypertension • New Hot Topics Markers • • • • • • • • microRNA / miRNA CRISPR CAS9 – gene editing Autophagy (2016 nobel Prize) CirculatingNucleic Acid&CancerCell Metagenome Nutrigenetic Telomere Multiple Gene variant & expression.

18. BIG TREND FOR CLINICIAN RESEARCH • Circulating markers • Circulating DNA, mRNA & MicroRNA • Multiplex Testing • Genetic Variation, Multiple cytokine, chemokine, etc • Applied new marker / reference interval cut off for diagnosis

19. MULTI OMICS IN MOLECULAR BIOLOGY • • • • • Genomics Epigenomics Transcriptomics Proteomics Metabolomics Holisticomics Metagenomics Pharmacogenomics Lipidomics Peptidomics Interactomics

20. KEY TECHNOLOGY FOR APPLICATIVE INTEGRATIVE RESEARCH Genomics, Epigenomics, Transcriptomics, Metagenomics Mass Array Digital PCR Gradient PCR Micro Array Realtime PCR Sanger Sequencing Pyro sequencing NGS PCR BIOINFORMATICS & DATA MANAGEMENT Atomic Trace element, Metabolomic, Proteomic, etc UV VIS HPLC UV/F LCMS QQQ LCMS QTOF xMAP Technology Flow cytometry FTIR IHC ELISA GCMS

21. THE NEW EPIGENETIC BIOMARKER OF AGING PROCEEDED ALONG THREE MAIN STEPS

22. NEW TREND IN DIABETIC • Correction HbA1c with age erythrocyte (MRBC) • Ambulatory Glucose (AGP)

23. IMPAIRED GLUCOSE TOLERANCE Alpha-hydroxybutyric acid (AHB) 4-methyl-2-oxopentanoic acid 4MOP Linoleoylglycerophosphoc holine Oleic acid β-hydroxybutyric acid Serine Pantothenic acid Glucose

24. COMPOSITION OF GUT MICROBIOTA Krzywinski M, Altman N. 2014. Nat Meth. 11(2):119–20

25. Include Vitamin D Early Feedings Probiotic supplementation Early Antibiotics Use Maternal – Fetal Interaction Infant Gut Microbiota Mode & place of Delivery Antigen load Microflora Hypothesis Allergy Hygiene Hypothesis Clinical expression of

26. HEALTH IMPLICATIONS OF GUT MICROBIOTA Nagpal, R., Yadav, H. & Marotta, F. Front. Med. 1, (2014)

27. THE SURPRISING GUT MICROBES OF AFRICAN HUNTER-GATHERERS (HADZA) WIRED at <https://www.wired.com/2014/04/hadza-hunter-gatherer-gut-microbiome/>

28. Autophagy - Aging Dirty Clean 28

29. Parkinson Alzheimer Clean Dirty Alpha-1 antitrypsin mutant 29

30. CLEANING PROSES AS QUALITY CHECK OF HUMAN CELL, ORGANELLE AND PROTEIN Apoptosis – Programmed Cell death – Maintain quality of Cell & extracellular debris Autophagy – Maintain Quality organelles or macromolecular intra Cell The Ubiquitin Proteasome Pathway – Maintain quality of Protein 30

31. CELLS MUST DISPOSE OF GARBAGE, TOO. THE MALFUNCTION OF WHICH CAN LEAD TO ALZHEIMER'S DISEASE AND CANCER 31

32. THE CONVERGENCE OF AUTOPHAGIC FLUX AND VASCULAR AGING 32 Nussenzweig, S.C., Verma, S. & Finkel, T. Circulation Research 116, 480–488 (2015).

33. Effects of Autophagy on Disease Progression Choi, A.M.K., Ryter, S.W. & Levine, B. NEJM, (2013). 33

34. METABOLOMIC hundreds of compounds using metabolomics proprietary technology & informatics to identify significant single metabolite or metabolic pathway abnormalities Amino acid metabolism disorders Fatty acid oxidation disorders Disorders of fatty acid transport Organic acidemias MNGIE (mitochondrial neurogastrointestinal encephalopathy) Certain mitochondrial disorders Pyrimidine disorders Purine disorders Neurotransmitter disorders (previously only diagnosed in CSF) Creatine disorders Bile acid disorders Urea cycle disorders

35. FATTY ACID PROFILE

37. Warren, H.R. et al. Nat Genet 49, 403–415 (2017).

38. Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk Warren, H.R. et al. Nat Genet 49, 403–415 (2017).

39. LIQUID BIOPSY

40. BIOMARKERS OF AGING Methylation Profile Telomere 8-oxoGsn DNA Risk (Variant) Autophagy markers Number of Stem cell Steroid hormone NK Cell

41. TERIMA KASIH