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 the age of 65 years, and for those residing in nursing
homes, the prevalence is closer to 50 percent. One distinction between
anemia 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 to some extent, early 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,
paraprotein, 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
Abbreviations and acronyms
used in this chapter include: EPSE, Established Populations for
the Epidemiological Study of the Elderly; HSC, hematopoietic stem
cells; IADL, independent activities of daily living; IL, interleukin;
LIF, leukemia inhibitory factor; NHANES, National Health and Nutrition
Examination Survey; OSM, oncostatin M; PAI-1, plasminogen-activator
inhibitor-I; TAFI, thrombin-activatable fibrinolysis inhibitor;
TCR, T-cell receptor; TF, tissue factor; TGF-β,
transforming growth factor-beta; Th, T-helper lymphocytes; TNF-α,
tumor necrosis factor-alpha; t-PA, tissue-type plasminogen activator;
WHO, World Health Organization.
Over the next several decades, the percentage of the population
older than the age of 65 years will ...