been found in several studies using rodents. In these studies, the effects of aging varied by source of the macrophage as well as the type of stimulus, and it has recently been sug- gested that the microenvironment in which the cell is located may be important in determining age-related changes (Kohut, Senchina, et al 2004; Stout and Suttles 2005). Thus, the ef- fects of aging on macrophages are ultimately due to changes both intrinsic and extrinsic to the macrophage itself (Gomez et al 2005). The diminished capacity of macrophages to pres- ent antigen or produce anti-pathogenic cytokines and reactive species may translate to increased survival and reproduction of the pathogen as well as increased host damage or death (Gon et al 1996; Miller 1996; Pawelec et al 1998; Zissel et al 1999; Looney et al 2002). Natural killer cells destroy infected cells through cyto- toxic granule release, similar to the activity of T cells though in a nonspeciﬁc fashion. Circulating numbers of NK cells increase with age and total NK cell pool activity appears to be maintained with aging; however, the per se killing capaci- ties and IFN-γ producing capacities of these cells appears to be impaired, perhaps due to an age-associated shift towards a “mature phenotype” (Solana et al 1999; Mocchegiani and Malavolta 2004; Plackett et al 2004). The response of aged NK cells to stimulation by IL-2 may be diminished (as is the case for proliferation, CD69 expression, Ca2+ mobilization, and some killing activities) or may be unaffected (as is the case for perforin induction or TNF-α production) (Borrego et al 1999; Solana and Mariani 2000). Age-associated de- fects in signal transduction may explain these observations (Borrego et al 1999). Production of IL-4 by NK cells appears to increase with age (Plackett et al 2004). Neutrophils are the most prevalent white blood cell in the human blood on a per cell basis. As phagocytic granulocytes, they play an important role in consuming (through phagocytosis) and/or destroying (through granule release) extracellular pathogens. Regarding these two functions, immunosenescence appears to enhance phagocytic capacity (Tsukamoto et al 2002), but its effects on neutrophil cytokine and granule release are less clear, as researchers have reported conﬂicting ﬁndings based on the stimulus employed and lifestyle factors (Miyaji et al 2000; Plackett et al 2004). Besides inﬂuencing cells of the innate immune system, immunosenescence is also believed to modulate several molecular systems associated with innate immunity, such as inﬂammation and complement (a component of inﬂam- mation), as described in the next section. Immunological outcomes of exercise in older adults Immunosenescence and inﬂammatory conditions Links between aging, immunosenescence, and diseases associated with inflammatory conditions have recently received great attention. Aging is associated with an increase in inﬂammatory processes (Boren and Gershwin 2004; Franceschi et al 2000b) and as such may represent a predisposing factor for the development of several aging/inﬂammation-associated diseases including neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease (McGeer and McGeer 2004) and autoimmune diseases such as diabetes, rheumatoid arthritis, and systemic lupus erythematosus (Hasler and Zouali 2005; Licastro et al 2005). Chronic inflammation may also predispose individuals to cancer (Licastro et al 2005; Sarkar and Fisher 2006). Elevated serum proinﬂammatory cytokines have been associated with increased risk of heart disease, high blood pressure, type II diabetes, and atherosclerosis (Paulus 2000; Mangge et al 2004; Wisse 2004; Aukrust et al 2005). The precise role that elevated proinﬂammatory cytokines play in these chronic diseases remains to be established and may vary by disease. At this point, it may be useful to view elevated serum inﬂammatory cytokines as an early marker of potential chronic disease and make appropriate lifestyle modiﬁcations to reduce disease risk. Complement is another molecular system associated with inﬂammation. Complement consists of plasma proteins that can automatically latch onto and destroy extracellular pathogens, either directly via formation of a membrane at- tack complex, or indirectly via opsonization, which induces other cells of the immune system to engulf the invader. Levels of complement proteins appear to increase with ag- ing (Waitumbi et al 2004). The effects of aging on comple- ment function are unclear, as different animal models have yielded different results. One study in rats demonstrated that efﬁciency of the complement system may diminish with aging (Lavery and Goyns 2002), but opposite ﬁnd- ings were reported from German Shepherd dogs (Strasser et al 2000). Age-associated inﬂammatory conditions as described earlier may promote complement activation and consequently disease states such as Alzheimer’s disease, Parkinson’s disease, and age-related macular degeneration (McGeer et al 2005). Immunosenescence and chronic infection Our discussion of immunosenescence has thus far focused on aging-induced changes to the immune system without Clinical Interventions in Aging 2007:2(1) 7