Senchina and Kohut consideration of the external environment. However, as people age they are more likely to acquire chronic infections such as varicella (the cause of chickenpox and shingles), Epstein-Barr virus (EBV, the cause of mononucleosis), or cytomegalovirus (CMV). Virological status is known to impact on immunity: chronic infection by these pathogens may alter the immune system and lead to consequences (immunosenescence) similar to those induced by aging directly (van Baarle et al 2005; Koch et al 2006). For example, most people are chronically infected with the herpes virus CMV (Bennekov et al 2004), acquired during infancy during breastfeeding (Schleiss 2006) or later in life via kissing, blood transfusion, or sexual intercourse (Frost 1996). Chronic CMV infection is associated with chronic activation of the T cell pool, leading to decreased naïve and early memory CD8 T cell pools and a polarization of the T cell response towards Th1 activity (Vescovini et al 2004; Akbar and Fletcher 2005; Almanzar et al 2005; Northﬁeld et al 2005). Older adult CMV carriers also respond less vigorously to inﬂuenza vaccine (Trzonkowski et al 2003). In contrast, chronic EBV infection does not elicit such polarized responses by the immune system but does alter T cell pools (Vescovini et al 2004). The presence of multiple chronic infections may impact on the ability of the body to ﬁght multiple viruses: in one study, it was found chronic CMV-infected impaired the ability of older adults to concomitantly manage chronic EBV infection (Khan et al 2004). IL-2 and IL-4 production by PBMC from CMV-infection older adults stimulated with PMA-ionomycin was lower compared with PBMC from noninfected age-matched controls, but this effect was not seen with IFN-γ (Almanzar et al 2005). Immunosenescence and nutrition Nutrition also impacts on immunosenescence (Lesourd 2004). In fact, some of the commonly reported age-associated changes of immune response such as lymphocyte prolifera- tion are not observed to the same extent in well nourished individuals (Molls et al 2005). The elderly often do not consume enough of both macro- (carbohydrates, protein) and micronutrients (minerals and vitamins) (Amati et al 2003; Ahluwahlia 2004). Numerous interventional studies have shown that macro- or micronutrient-supplementation may be able to restore immune function in elderly (High 2001). Independent, healthy adults supplemented with trace ele- ments and vitamins demonstrated enhanced NK and T cell functions compared with placebo-treated peers (Chandra 1992). Daily multivitamin consumption in this population has been associated with increases in IL-2 (Chandra 1992; Kohut et al 2002). Institutionalized elderly given selenium sulﬁde, zinc sulfate, and vitamins exhibited increased antibody titer following inﬂuenza vaccination (Girodon et al 1999). Clinical consequences of immunosenescence Immunosenescence has numerous and varied clinical con- sequences as have been hinted by the preceding discussion; in summary: (a) increased morbidity and mortality to bac- terial and viral infection (Bender 2003; Falsey and Walsh 2005; High et al 2005; Nichol 2005); (b) decreased vaccine effectiveness (Grubeck-Loebenstein et al 1998; Castle 2000; El Yousﬁ et al 2005; McElhaney 2003; Nichol 2005); (c) increased incidence of autoimmune disease and related inﬂammatory conditions (Franceschi et al 2000b; Wick et al 2000; McGeer and McGeer 2004; Hasler and Zouali 2005; Licastro et al 2005); and (d) increased incidence of cancer (Ben-Yehuda and Weksler 1992; Licastro et al 2005; Sarkar and Fisher 2006). These phenomena are the direct or indirect results of many of the changes to both the innate and adaptive immune systems associated with immunosenescence. Regarding innate immunity, impaired macrophage func- tions may protract the infection process, leading to increased pathogen longevity and greater potential for harm to the host. More data in humans is needed to assess the effects of immunosenescence on the functions of DCs, NK cells, and neutrophils as ﬁndings thus far are heterogeneous; however, it is likely immunosenescence impacts on the function of these cell types as well. Aging is associated with increased inﬂammatory (Franceschi et al 2000b; Boren and Gershwin 2004) and complement (Waitumbi et al 2004) activities. In addition to possibly predisposing elderly individuals to cancer or autoimmune/inﬂammatory conditions (discussed earlier), increased basal states of inﬂammation may also hamper the development or resolution of immune responses to pathogens. Regarding adaptive immunity, the decreases in B cell/ plasma cell number, function (antibody production), and proliferation could all translate to a blunted adaptive immune response to pathogen, leading to increased severity and time span of infection. A similar scenario has been evoked for T cells; in this instance, immunosenescence is associated with decreased co-stimulatory and killing activities. In addition, the depleted naïve T cell pool (Almanzar et al 2005) associ- ated with aging may result in fewer naïve cells being capable of responding to antigen; indeed, the expanded memory pool 8 Clinical Interventions in Aging 2007:2(1)