We are currently experiencing, and will continue for the next two decades to experience, a rapid expansion of the percentage of the population older than 65 years of age.1–3 In anticipation, an increased effort is underway to better understand the basic biology of aging and the mechanisms whereby individuals become susceptible to disease.4,5 In this chapter, a current appraisal of our understanding of aging and aging hematopoiesis is presented followed by a more detailed discussion of the clinical consequences of these age-associated changes in hematopoiesis.
Acronyms and Abbreviations
AGM, aorta-gonad-mesonephros; ASCT, autologous stem cell transplant; CHIP, clonal hematopoiesis of indeterminate potential; CHS, Cardiovascular Health Study; CRP, C-reactive protein; DR, Dietary Restriction; EPESE, Epidemiological Study of the Elderly; HSC, hematopoietic stem cell; HSCT, hematopoietic stem cell transplant; IADL, instrumental activities of daily living; IL-6, Interleukin-6; LMNA, Lamin A; MDS, myelodysplastic syndrome; NHANES III, National Health and Nutrition Examination Survey; NK, Natural Killer; OSM, oncostatin M; PAI-1, plasminogen activator inhibitor-1; TAFI, Thrombin activatable thrombolysis inhibitor; TCR, T-cell receptor; TF, tissue factor; TGF-β, transforming growth factor-beta; TH, T helper cell; TNF-α, tumor necrosis factor- alpha; tPA, tissue plasminogen activator; UA, unexplained anemia; VA, Veteran’s Administration; VAF, variant allele fraction; VWD, von Willebrand Disease; WBC, white blood cell; WES, whole exome sequence; WHO, World Health Organization
A central dogma in gerontology is that aging is not a disease. One common feature of aging is that for any measurable variable, the range of values among normal individuals in an aging population is much wider than that for younger individuals. Although functional declines that accompany normal aging have been well characterized,6 in general, these are not of sufficient magnitude to account for symptoms or be mistaken for disease. For example, that kidney function declines with age is well recognized and currently appreciated.7–9 Yet the clinical consequences of this change in renal function, in the absence of a disease or the exposure to an exogenous nephrotoxic agent, do not occur commonly.
Similarly, the character of the marrow changes with age (detailed later). Marrow stem cells increase in number and proliferative capacity, yet the in vitro proliferative potential of progenitor cells is less.10–12 Although clinically significant cytopenias do not occur in the absence of disease, mild to moderate anemia that has not been fully characterized occurs with increasing frequency, especially in frail older adults.13,14 Furthermore, in frail individuals even a mild reduction in hemoglobin level has been associated with untoward clinical outcomes.15–17
Certain immune functions decrease with age,18,19 but these may be of only marginal clinical significance. For example, whether the laboratory-observed declines in immune function contribute to a heightened susceptibility to infection is a subject of debate, but data support an association of age-associated qualitative change in lymphocyte function and susceptibility to ...