VA Office of Research and Development
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.
Significance to VA: Sedentary behavior has emerged as a major risk factor for chronic conditions that are highly prevalent among older Veterans, including obesity, diabetes, and cardiovascular disease Innovation and Impact: Exercise is the cornerstone of rehabilitation and is an essential part of treatment plans for these conditions; however, our understanding of why certain individuals respond positively to exercise while others do not remains unclear. Epidemiological findings indicate that adhering to established exercise guidelines does not lower multimorbidity rates or mortality risk in in…
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…
To minimize sedentary behavior and increase physical activity the investigators will use our SLIMM intervention. The goal of SLIMM is to replace 1 hour/day of sedentary duration with casual walking time. This goal is \~10% of the average baseline sedentary duration of 10.8 hours/day. While SLIMM is not anchored to a fixed percentage or step count increase, it operationalizes this goal through behavioral coaching and activity monitoring focused on increasing stepping time throughout the day. The SLIMM target duration for decreasing sedentary duration by 1 hour/day is based upon potential impact on energy expenditures and mortality from our previous National Health and Nutrition Examination Survey (NHANES) publication on sedentary behavior in patients with multimorbidity.
The novel naturally derived activator of Nrf2, PB125, contains extracts from three botanical sources including i) Rosmarinus officinalis, standardized to carnosol content of 6%, 68 milligrams (mg) of extract; ii) Withania somnifera (aka Ashwagandha), standardized to withaferin A content of 1%, 23 milligrams (mg) of extract; and iii) Sophora Japonica, standardized to luteolin content of 98%, 9 milligrams (mg) of extract. Each extract can increase the nuclear translocation of Nrf2 and when combined, these extracts act in synergy through multiple control points to amplify and prolong the activation of Nrf2.
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