Immunobiology of Aging

Fathman, Charles

Abstract

The immune system is profoundly affected by aging. Older individuals are at higher risk of death and disability from infections and cancer. The reason for such disproportionate susceptibility appears to be age-attributed impairment or suboptimal performance of immune system. Such age-attributed immune dysfunction might have a hidden role in other disease states such as chronic inflammatory diseases (COPD or rheumatoid arthritis) and degenerative diseases such as atherosclerosis and osteoarthritis. Yet, systematic efforts to understand the role of aging on immunological mechanisms are lacking. There are two reasons for this. The first is absence of well-defined set of immunological measures that are easy to perform but comprehensive in scope. A well-defined battery of such tests, similar to those for renal or hepatic function, would allow one to characterize the functional status of immunity (innate, adaptive or even aberrant) in varied settings including old age, health and disease. The second reason is the absence of understanding of what constitutes 'normal'immunobiology of aging in the general population Our proposal would have one overriding aim: To develop and make available to other investigators a control healthy subject registry and immune profile database and bio-specimen repository developed from a cohort of at least 1100 normal healthy individuals. The dataset will comprise a cross-sectional analysis of the local San Francisco Peninsula general population between the ages of 20 and 90 (representing equal gender and representative ethnic population, and equal distribution by decade of life). The registry will contain demographic data, race/ethnicity, prescribed medications, over the counter medications, vitamins, alternative therapies, physical function questionnaire, alternative contact person, and HIPPA release. Fasting blood will be obtained for immune phenotyping as described in Specific Aim 3 the immune profile will contain the results of both conventional and novel immune profiling assays to develop the normative immune profile of aging (using PBMC subset analysis, cytokines, and activation induced signaling of PBMCs for phosphoepitope and gene expression analyses). Data from these analyses will be useful in identifying biomarkers of the normal immune profile associated with aging as well as correlation with phenotypic aspects of aging such as sarcopenia and disability The immune profile (as well as normal blood chemistries and demographic data) of these subjects will be made available to serve as the basis for future longitudinal study of change in the immune profile over time in association with the development of co-morbidities associated with aging. The primary deliverable for this proposal will be a unique open access electronic data repository that has phenotypic information in multiple scales (epidemiological, and clinical, and, at the cell and molecular level, of immune phenotype) and genetic and proteomic information (gene and protein expression of resting and activated PBCs) on 1100 healthy individuals at different ages from 20 to 90 years. This resource will enable a systems-based approach to the immunology of aging.

Public Health Relevance

Our proposal is an initiative of the new Stanford Institute of Immunity, Transplantation and Infection (ITI) to develop an immune profile of normal healthy subjects throughout 7 decades of life consisting of a cross sectional analysis of 1100 normal individuals representing equal distribution of gender and from age 20 to 90. Demographic data and normal lab chemistries will be obtained from each individual as well as their immune profile using instrumentation and technology available in the Stanford Human Immune Monitoring Center. We will develop an open-access data repository that will enable free sharing of high throughput analyte data and appropriately de-identified phenotypic data on a web-based platform using high quality open source and statistical tools.