Prostate cancer is diagnosed in approximately 16% of U.S. men, at a median age of 67 years, and the survival rates are high. Survivors are likely to experience poorer quality of life (QOL) due to the long-term side effects of treatment that are coupled with age-related declines in physical, mental and social functioning. Fatigue is one of the most commonly reported symptoms in prostate cancer survivors, but it is also one of the least understood cancer-related symptoms. Fatigue is associated with psychological distress, disruptions of sleep quality, and impairments in health-related QOL. Inflammatory processes and changes in the hypothalamic- pituitary-adrenal (HPA) axis and autonomic nervous system may also play a role in cancer-related fatigue. Thus, effective treatments for fatigue in elderly prostate cancer survivors are urgently needed. Prior research has shown that Tai Chi Qigong (TCQ), a mind-body exercise intervention, can improve physical and emotional health. However, no definitive clinical trial has demonstrated its efficacy compared to activity-matched and health education control groups as a treatment for fatigue in senior, inactive prostate cancer survivors. Therefore, we propose to conduct a randomized controlled trial of TCQ for reducing fatigue in prostate cancer survivors. This mind-body exercise intervention focuses on deep breathing techniques, slow deliberate movements, holding specific postures, and meditation to induce relaxation. In this trial, 210 elderly prostate cancer survivors (≥ 60 years) with fatigue will complete either a TCQ, streching movement or health education class. Classes will be held for 60 minutes, twice a week, over a 12-week period. Guided by biopsychosocial and psycho-neuroimmunology models we will test the hypotheses that a TCQ intervention, as compared to stretching movement or health education, will: 1) reduce fatigue (primary outcome) in inactive, elderly, prostate cancer survivors; 2) reduce inflammation as indexed by a vertically integrated approach: systemic levels of pro- and anti-inflammatory cytokines (ELISA), Toll-like receptor (TLR)-4 stimulated monocyte production of inflammatory cytokines, activation of inflammation-related transcription factors (e.g., NF-κB) and gene expression profiling with promoter based bioinformatics; and 3) regulate the expression of genes from two major functional clusters previously found to be associated with fatigue in prostate cancer patients: a) inflammation, vasodilation and metabolite sensing and b) energy and adrenergic activation. Measurements (baseline, 6-week midpoint intervention, and 1-week, 3-months, and 12-months post-intervention) will assess fatigue as well as potential mediating factors including psychological distress, mental and physical QOL, sleep quality, perceived stress, physical activity, and social well being. We hypothesize that relative to the streching movement and health education control conditions, TCQ will result in improvements in...