may actually prohibit respondent naïve cell populations from proliferating and expanding to adequate numbers. Exercise and immunosenescence Considering all the impacts of immunosenescence on immu- nity in aged individuals, clinicians, physicians, and research- ers alike are intensively investigating therapies to ameliorate these consequences. Exercise is one therapy that has received much scientiﬁc attention, both for its effectiveness and logistical advantages over other therapies (such as calorie restriction, dietary or herbal supplementation, endocrine modulation, immunomodulation, or additional vaccination). Compared with other modes, the advantages of exercise are manifold: low-cost, noninvasive, easy to implement, and amenable to being practiced in either home or clinical settings (Gueldner et al 1997; Kohut and Senchina 2004). Further, exercise prescribed for one ailment may beneﬁcially impact other chronic diseases, including arthritis, heart disease, stroke, peripheral vascular disease, diabetes, osteoporosis, and pulmonary disease (Bean et al 2004). Risk of infection and exercise in the elderly If exercise can delay or attenuate the process of immunose- nescence, a clinical beneﬁt that one may expect to observe is a reduction in the incidence or severity of infectious disease. Data in support of this possibility among older adults are limited, yet the data from both clinical exercise intervention trials and epidemiological studies lend some support. One large study that included older as well as younger adults demonstrated that the risk of community-acquired pneumonia decreased with increasing physical activity in women (Baik et al 2000). In a separate study, women aged 55 to 80 were followed for a period of 6 years, and physical inactivity was associated with an increased risk of hospitalization due to infection (Leveille et al 2000). Kostka and colleagues (2000) followed adults aged 66–84 for one year to assess both the number of upper respiratory tract infections (URTI) per year and the number of days with URTI. Physical activity was assessed with a questionnaire and aerobic ﬁtness level (VO2max) was measured. Sports activity negatively correlated with both number of URTI episodes per year and number of days with URTI, but VO2max did not correlate with URTI. The greatest protection from URTI appeared to be associated with higher levels of activity (equivalent to jogging 7 km/day or walking 90 minutes per day at a speed of ~ 19–20 minutes per mile) (Kostka et al 2000). Immunological outcomes of exercise in older adults Several exercise intervention trials have also examined URTI. In one of the longest intervention trials (10 months), older adults assigned to a moderate-intensity exercise pro- gram 3 days per week had fewer days of self-reported URTI symptoms, but not episodes of URTI as compared with sub- jects not participating in regular moderate intensity exercise (Kohut and Senchina 2004). Two intervention studies of shorter durations reported conﬂicting results. Over a 12 week period, highly conditioned subjects and women participat- ing in a 12 week walking program had a lower incidence of URTI as compared with a control group (Nieman et al 1993). In contrast, a 10-week moderate to vigorous exercise intervention was not associated with decreased URTI in older women (Fahlman et al 2000). Importantly, it may have been difﬁcult to detect an effect of exercise in this study due to a relatively small number of subjects and a short exercise- training period (10 weeks). The exercise intervention studies previously described included relatively healthy, independent older adults, and the ﬁndings generally suggest that exercise has some beneﬁt with respect to reduced incidence or severity of infection. Only one study has evaluated the impact of exercise on infection in frail, nursing home residents. An 8-month exercise program did not alter the incidence of infection among frail adults (Schnelle et al 2002). The data are too limited to draw any conclusions at this point, but it is possible that once older adults have become frail, they may not be capable of exercise that is intense or prolonged enough to impact immunity. Frailty status has been associated with some speciﬁc immune alterations (Leng et al 2002; Schmaltz et al 2005; Semba et al 2005), and perhaps once a state of frailty has developed, it may not be possible to reverse these immunological changes through exercise. Additional studies with frail participants are needed to better evaluate the extent to which exercise might impact resistance to infection. Finally, it is worthwhile to mention that younger adults who exercise strenuously appear to have an increased risk of infection (Nieman 1998). To our knowledge, this relation- ship between intense exercise and infection has not been demonstrated in older adults. It may be difﬁcult to examine this possibility due the very limited number of older adults that exercise at extremely high volumes or “overtrain”. In response to a single session of intense exercise (running a marathon), T cell responses decline, yet the degree of decline is similar in young as compared with older adults (Henson et al 2004). To summarize, it appears that moderate exercise may have beneﬁts in terms of reduced incidence of infection Clinical Interventions in Aging 2007:2(1) 9