By Rafat Abonour, MD

2008-12-06

This morning at 9:30 a.m. in 304-306-308 – South, Dr. Dan L. Longo, of the National Institute on Aging, will chair a provocative session on aging and hematology and examine the normal and abnormal manifestations of aging in the marrow and blood.

Dr. Margaret A. Goodell, of the Baylor College of Medicine in Houston, will describe how stem cells markedly decline in function with time, and they display characteristic behaviors such as skewing of differentiation toward myeloid development. Her laboratory has used gene expression profiling to examine the global gene expression changes that occur in hematopoietic stem cells in aging in mice. Of around 14,000 genes profiled, they identified about 1,500 that were age-induced and another 1,600 that were age-repressed. Genes associated with the stress response, inflammation, and protein aggregation dominated the up-regulated expression profile, while the down-regulated profile was marked by genes involved in the preservation of genomic integrity and chromatin remodeling. The dysregulation was in gene clusters rather than alterations of a small number of aging-specific genes. Is this due to extensive epigenetic changes over time? Perhaps, and this could promote secondary events that may increase propensity for neoplastic transformation with age. Moreover, it appears that the aging environment influences stem cell functions. The composition of the bone marrow changes with age. Dr. Goodell will present a comprehensive view of influence of bone marrow environment on aging of stem cells.

Dr. Amy J. Wagers, of the Joslin Diabetes Center in Boston, will discuss how aging causes deterioration of tissue function and suggests that loss or functional impairment of tissue-specific stem cells directly contributes to age-dependent failures in tissue repair. Moreover, the effects of aging on tissue stem cell function appear to arise at least in part from alterations in the aged-tissue environment, which can inhibit stem cell activity in older animals and may be regulated by factors that circulate naturally in the bloodstream. These investigators have identified a discrete set of metabolic regulators and inflammatory cytokines, which may alter the signals that stem cells receive from their environment in aged animals. Will the knowledge gained from these ongoing studies help to define novel strategies to delay or reverse the onset of age-related disease, extending the healthful life? So we wish.

Dr. Longo will discuss the progressive dysregulation of homeostatic equilibrium and emphasize the role of inflammation and its relation to anemia. He notes that even extremely healthy older individuals are affected by a mild pro-inflammatory state marked by high levels of pro-inflammatory markers, such as IL-6 and C-reactive protein (CRP). Four mechanisms by which inflammation may affect anemia will be discussed. These involve inhibition of proliferation of erthyroid progenitors, blunt response to erythropoietin, higher levels of hepcidin, and reduced erythrocyte survival.

Understanding the role of the microenvironment in the aging of hematopoietic stem cells as well as the role of epigenetics, genetic stability, DNA damage, and telomerase organization in cellular senescence may help expand the field of regenerative medicine. Yes, it may also help get rid of the extra fat deposited in the bone marrow among other places.

If you miss this session this morning, it will be offered again this afternoon at 4:30 p.m. in the same location.

Dr. Abonour indicated no relevant conflicts of interest.

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