Internal Aging Index based on Gene Expression Profiling of Immune Cells

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1 V Test Report for: 00X-M000XXX Sample Submitted by : PCR ver. Internal Aging Index based on Gene Expression Profiling of Immune Cells Test Result Young? Old? V No.15049

2 Test Result Personal Data Test ID Actual Age Sampling Date Completion Date : 00X-M000XXX : 43 : 05/26/2015 : 06/09/2015 Test Result Your ImmunAge is 43 (40s ranking:top 17 / Among 36) Your ImmunAge was computed as 43 years old. The activity of your immune system is ageappropriate. Maintain your vitality through healthy life style. Persons in Charge Supervision: Mitsuru Emi, MD, PhD Medical Genetic Specialist Experiment:Masayo Yamauchi, AS Analysis:Junpei Hata, BS Quality Management:Ken Nonaka, MS 1/8

3 V Your Position among Your Age Group 20s 30s Young Old 40s You are here V 50s 60s 70s 2/8

4 Role of Major Immune Cells ImmunAge reflects activity of immune cells, which travel through our blood and fight against pathogens like bacteria and viruses. Innate Immunity Adaptive Immunity Signal* 1 Naive CD8+ TCell Macrophage Innate Immunity Naive CD4+ Foreign objects Dendritic Cell Signal Alert the presence of foreign objects to other immune cells. Differentiation* 2 NK Cell * 3 Attack NKT Cell * 4 Attack CD8+ * 5 CD4+ * 6 Signal Differentiation Signal Virus-infected cells and cancer cells Macrophage Memory CD8+ Recognize and memorize the initial attack and prepare for subsequent encounter. Memory CD4+ Differentiation Memory B Cell B Cell Antibody* 7 Production Engulf and digest dead cells, bacteria, viruses, etc. Attack Bacteria *1 Direct signaling through cell contact or release of signaling molecules. *2 Change of cells in terms of function and morphology to become more specialized cells. *3 Natural killer cell. Effector of innate immunity. *4 NKT cell has characteristics of both NK cell and T cell. *5 Cytotoxic T cell. Attack virus-infected cells, cancer cells, etc. *6 T helper cell. Produce cytokines (signaling molecules). *7 Antibody recognizes specific antigen and let other immune cells know that it is a target. 3/8

5 Background information ImmunAge is an internal body aging index calculated from gene expression profiling of immune cells DNA Chip Research Inc. has been investigating gene expression pattern (RNA profile) of blood samples from healthy individuals from a wide range of age (20s - 70s), and discovered biomarkers that correlate with aging pattern. RNA in our blood mainly originates from immune cells, and age-related biomarkers we identified are very likely to reflect the activity of immune system itself. We have developed a method to calculate internal body aging index based on RNA expression profiles of age-related biomarkers, and named it ImmunAge. ImmunAge is dynamic, and should help you to monitor your health condition over time. Glossary RNA:Abbreviation for ribonucleic acid. Many cellular activities are regulated by function of proteins. Protein is synthesized accordingly to the genetic information carried by RNA, which is a complementary copy of DNA. Unlike DNA, which is a static genetic code, RNA is produced only when, where and at an amount the cells need. Synthesis of RNA precedes that of protein, thus dynamic fluctuation of RNA production, or gene expression pattern, is what eventually regulates many cellular processes. 5/8

6 Nature of ImmunAge ImmunAge reflects actual aging. ImmunAge (PCR version) is compiled from expression pattern of five age-related genes. ImmunAge and actual age shows positive linear correlation. Changes in immune function with aging are closely related to onset of various age-related diseases. By knowing your ImmunAge, you can objectively assess your internal aging status. Correlation of ImmunAge and actual age of 151 healthy individuals Actual age 5/8

7 How was the Test Done? 1. Experiment (1) Extract nucleic acid (RNA) from blood sample. U U U Lyse blood cells and extract RNA. Most RNAs in blood originate from immune cells. (2) Quantitate RNA of age-related genes. Measure the amount of RNA of 5 age-related genes, using quantitative PCR. 2. Analysis Calculate ImmunAge with our proprietary algorithm. Compute ImmunAge based on originally-developed algorithm. Actual age 7/8

8 Recommendation on periodic check up ImmunAge reflects your current health condition, and by checking your ImmunAge periodically, you can monitor your internal health and possibly allow you to detect illness early. Reference (1) Immunology Jul;133(3): The stromal cell antigen CD248 (endosialin) is expressed on naive CD8+ human T cells and regulates proliferation. (2) Mol Cancer Ther Aug;7(8): Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248. (3) Genes Immun Jun;6(4): Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data. (4) Blood May 7;113(19):e1-9. A HaemAtlas: characterizing gene expression in differentiated human blood cells. (5) J Interferon Cytokine Res Oct;34(10): Isthmin 1 is a secreted protein expressed in skin, mucosal tissues, and NK, NKT, and th17 cells. (6) Mol Biol Rep Jun;41(6): Elevated neurofilament light chain (NFL) mrna levels in prediabetic peripheral neuropathy. (7) Proc Natl Acad Sci U S A Nov 1;88(21): Cysteine-rich intestinal protein binds zinc during transmucosal zinc transport. (8) J Biol Chem May 9;283(19): Characterization of human SLC4A10 as an electroneutral Na/HCO3 cotransporter (NBCn2) with Cl- self-exchange activity. Information last updated: July /8

9 Contact Us RNA Check Support Center Kaigan, Suzue Baydium 5F Minato-ku, Tokyo , Japan TEL : FAX : rnacheck-support@dna-chip.co.jp URL : Registered Clinical Laboratory (License No. 940)

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