Physical Activity Modifies Exercise Responsiveness

Exercise is the cornerstone of rehabilitation and an essential part of treatment plans for many chronic conditions; however, our understanding of why certain individuals respond positively to exercise while others do not remains incomplete. Physical inactivity and sedentary behavior have reached epidemic levels, coinciding with alarmingly high levels of multimorbidity in Veterans that, the investigators believe, impair exercise responsiveness and rehabilitation efficacy by disrupting the regulation of redox homeostasis and redox signaling by the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2). This project will use complementary approaches including 1) the Sit Less, Interact, Move More (SLIMM) intervention, and 2) PB125 to target Nrf2 and break the cycle of sedentary behavior, redox stress, functional impairments, and worsening multimorbidity in older Veterans.

Inclusion Criteria: 1. Physically inactive, ≤5,000 steps/day 2. Multimorbidity Weighted Index between 6 to 11 3. Ability to sign informed consent 4. Montreal cognitive assessment (MOCA) exam score ≥26 5. Free-living and ambulatory prior to admission Exclusion Criteria: 1. Multimorbidity Weighted Index \< 6 or \> 11 2. Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma 3. Currently on a weight-loss diet or body mass index (BMI) \> 35 kilograms per square meter (kg/m2) (a BMI of 35 kg/m2, which includes individuals that fall into to the Class I obesity category, has been selected to improve inclusion and generalizability to a greater percentage of the general population) 4. Human immunodeficiency virus (HIV) or hepatitis B or C 5. Recent anabolic or corticosteroids use (within 3 months) 6. Subjects with hemoglobin or hematocrit lower than accepted lab values 7. Alcohol abuse (\> 2 drinks per day) or drug abuse (inappropriate use of prescription medications or use of any illicit/illegal drugs for recreational use) 8. Unwilling to cease dietary supplements 4 weeks prior to initiation intervention