This chapter presents a current appraisal of our understanding of aging followed by a more detailed description of age-associated changes in hematopoiesis and their clinical consequences. Those who are older than the age of 75 years comprise a rapidly growing segment of the population. Marrow, like other organs, undergoes characteristic changes with advancing age, and many of these changes are evident by standard examination. For example, within the marrow space, hematopoietic cells occupy approximately one-half the volume at mid-life, with adipose tissue making up the difference. Yet, in the absence of disease, blood counts are generally maintained within a range established as normal for younger individuals. This is possible because hematopoietic stem cells increase in number with age and are of sufficient functional capacity to respond to homeostatic signals. Older people are more likely to have chronic diseases that may produce additional stress on marrow reserve. Anemia, for example, is present in just over 10 percent of community-dwelling individuals older than age 65 years; for those residing in nursing homes, the prevalence is closer to 50 percent. One distinction between anemias in older people compared with younger people is that for approximately one-third of older anemic patients, a specific cause for the anemia cannot be determined. This “unexplained anemia” is likely the result of multiple factors, including inappropriately low erythropoietin response, inflammatory cytokines, androgen deficiency, and, in some persons, incipient myelodysplasia. Platelet and neutrophil changes with age have been incompletely characterized but are likely to be subtle and of little clinical consequence. There is a well-characterized, age-associated involution of the thymus gland that precedes the histologic changes within the marrow, and marrow-derived T- and B-cell precursors are affected. Older people have fewer naïve, reactive T cells and an increase in relatively inert memory T cells. Thus, the capacity to react to new antigenic challenges is reduced and there is an increased susceptibility to certain infections and vaccines. Also evident are deficient regulatory functions, which may explain the observed increase in autoantibody, paraproteins, and inflammatory cytokines in those of advanced age. In the absence of disease, however, these alterations are of little consequence. In the presence of chronic debilitating disease, they are likely to become more pronounced and as such, contribute to an exaggerated decline in overall function. Similar conclusions can be drawn regarding dysregulated inflammatory pathways and coagulation. In balance, advancing age is associated with a procoagulant profile that may be of clinical importance in the presence of underlying atherosclerotic vascular disease.
Acronyms and Abbreviations:
EPESE, Established Populations for the Epidemiological Study of the Elderly; HSCs, hematopoietic stem cells; IADL, independent activities of daily living; IL, interleukin; NHANES III, National Health and Nutrition Examination Survey III; PAI-1, plasminogen activating inhibitor-I; TNF, tumor necrosis factor; UA, unexplained anemia; WHO, World Health Organization.
The world’s population is aging at an unprecedented rate and the implications for health ...