Multiple exercise intervention trials have been conducted in older adults ranging from several weeks up to two years. A variety of exercise types have been tested including cal- isthenics and strength training, although the majority of the studies used cardiovascular exercise at a moderate intensity. Generally, the longer-term interventions have observed im- provements of immune function. For example, 12 months of exercise including both resistance (60 minutes/week) and endurance (60 minutes/week) components resulted in increased salivary IgA levels (Akimoto et al 2003). The au- thors suggested that the increased salivary IgA may protect against upper respiratory infection, although URTI incidence was not measured in the study. Another long-term (2 year) intervention demonstrated that elderly women who partici- pated in the 2 year program had greater lymphocyte IL-2 production than a control group (Drela et al 2004). This is an important ﬁnding given that an age-related decline in IL-2 is well-documented in humans and animal models. Unfor- tunately the 2 year study did not assess cytokine production in the subjects before starting the intervention, and therefore the possibility remains that this group of subjects had greater IL-2 production at the beginning of the program. The impact of exercise on immune response to inﬂuenza vaccination was also evaluated in older adults. Vaccine efﬁcacy has been shown to be reduced with advancing age and therefore, an exercise-induced improvement in response to the vaccine could have important clinical beneﬁts. A 10-month program of exercise at a moderate intensity (65%–75% of maximal heart rate) resulted in a greater increase in antibody titer at 1 and 3 months post-immunization as compared to adults who were sedentary or participated in low-intensity exercise (Kohut, Thompson, et al 2004). In addition, the granzyme B activity was also greater in the subjects who participated in the exercise intervention. Granzyme B levels reﬂect cytolytic T cell function (CTL), and if an individual was to become infected with the inﬂuenza virus, CTL effector function is critical in clearing the infection. Several shorter term interventions (10 weeks–6 months) involving either cardiovascular exercise at a moderate inten- sity (50%–70%) or resistance training (3 sets of 8 repetitions per set) did not signiﬁcantly increase NK cell function, T cell proliferation, the number or percentage of CD3+, CD4+, CD8+ lymphocytes, IL-2 production, or delayed type hy- persensitivity (DTH) response (Nieman et al 1993; Rall et al 1996; Flynn et al 1999; Woods et al 1999; Fahlman et al 2000; Bermon et al 2001). However, a trend toward increased lymphocyte proliferation and NK cytotoxicity was observed in Immunological outcomes of exercise in older adults the 6 month training study (Woods et al 1999). In general, it appears that the longer term interventions (~1 year) are more likely to demonstrate a signiﬁcant impact on immune function, yet one shorter term study (16 weeks) observed improved NK cytotoxicity. Further research is clearly needed to determine the appropriate type of exercise, dose and intensity of exercise, the time period required before improvements are observed, and whether exercise-induced immune alterations result in clinical beneﬁts (fewer or less severe infections). To our knowledge, only two exercise intervention trials have involved the frail elderly. The results of these studies were not promising. An 8-month exercise program involving functional endurance and resistance training had no effect on lymphocyte proliferation to the mitogen PHA, lymphocyte activation markers (CD25, CD28, HLA-DR) or lymphocyte populations. The program was effective in improving per- formance of physical tasks such as distance walked (Kapasi et al 2003). A separate study that also involved a variety of exercises (ﬂexibility, strength, endurance, coordination) for 17 weeks failed to increase the delayed-type-hyphersensi- tivity (DTH) response to 7 antigens, but tended to attenuate the decline in the response over time (although this did not reach statistical signiﬁcance). In contrast to the longer-term studies in nonfrail elderly, exercise did not signiﬁcantly improve immune response. The intensity and duration of endurance exercise was lower in the frail elderly, but may be at the limit at which they could perform. It is also possible that longer-term interventions are required in this population before signiﬁcant changes are detected due to the limited functional capacity. Perhaps the immune alterations that occur in the frail state cannot be reversed. Certain immune alterations have been observed in the frail elderly (discussed in the next section). At this point, it is premature to draw any deﬁnitive conclusions regarding frail older adults based on only two studies, and further research with this population is needed. Immune and inﬂammatory markers of mortality/frailty Aging has been associated with numerous changes in both the number and percentage of cell types, as well as changes in function. More recently, some of these alterations have been linked to the frailty phenotype. For example, frailty status is predicted by higher levels of CD8+ CD28– cells (Semba et al 2005). CD28 is an important co-stimulatory molecule for T cell activation, yet it is not known how CD28 expression is related to frailty. Poor lymphocyte proliferation is also Clinical Interventions in Aging 2007:2(1) 11