GetHealthy-OA: A Program to Improve Pain and Function for Patients With Knee Osteoarthritis, Obesity, and Depression

Inclusion Criteria: * Mild to moderate knee osteoarthritis (Kellgren/Lawrence Grade II or III) * Obesity (Body Mass Index \> 30 kg/m2) * History of concurrent psychotropics for \< 2 weeks prior to initiation of treatment or on stable doses for \> 6 weeks * Access to an internet-enabled computer/smart phone * Willingness to comply with the study protocol and assessments * Cleared by a medical doctor to participate Exclusion Criteria: * Rheumatoid arthritis * History of cancer within 5 years of screening; unable to walk/wheelchair-bound * Prior surgical fixation of a femur or tibia fracture * Taking high doses of opioid pain medication (\>50 milligrams of morphine equivalent per day) * Diagnosis of a medical illness expected to worsen in the next 6 months (e.g., malignancy) * Active suicidal ideation or past-year psychiatric hospitalization; non-English speaking * Lifetime history of schizophrenia, bipolar disorder, or other psychotic disorder * Current substance abuse or dependence (or a history within the past 6 months) * Practice of yoga/meditation, or other mind body techniques once per week \> 45 min within the last 3 months * Engagement in regular moderate or vigorous physical exercise for \>30 min daily * Reduced or altered capacity due to administration of any mind-altering substances such as tranquilizers, conscious sedation or anesthesia, or brain injury * Females who are nursing, pregnant or planning to become pregnant during the duration of study drug dosing * Females or males who do not wish to abstain from sex or use contraceptive protection during study drug dosing and for 2 weeks after the last dose o Those not willing to use 2 of the following effective forms of contraception: sterilization surgery, intrauterine device (IUD), implantable rod, contraceptive shot/injection, oral contraceptives, patch, vaginal ring, diaphragm with spermicide, sponge with spermicide, cervical cap with spermicide, and/or a male or female condom * Subjects who do not have the capacity to consent themselves * Subjects who are unable to tolerate oral medication * Subjects having previously undergone any of the following treatments in the stated time window. * Surgery on the Study Knee in the past 6 months * Partial or complete joint replacement in the study knee. Partial or complete joint replacement in the contralateral knee is acceptable as long as the surgery was performed at least 6 months prior to enrollment and the operative knee is asymptomatic * Patients who have undergone arthroscopic surgery (including microfracture and meniscectomy) on the Study Knee in the last 2 years prior to the Screening visit or are anticipated to have arthroscopic surgery on either knee at any time during the study period * Currently taking Losartan * Currently taking Warfarin or related anticoagulants * Senolytic agents taken within the past 6 months and are not willing to discontinue these medications through the duration of the study, including: Fisetin, Quercetin, Luteolin, Dasatinib, Piperlongumine, or Navitoclax * Drugs that induce significant cellular stress and are not willing to discontinue these medications through the duration of the study, including alkylating agents, anthracyclines, platins, other chemotherapy drugs * Medications that are sensitive substrates or substrates with a narrow therapeutic range for cytochrome P450 family 1 subfamily A member 2 (CYP1A2), cytochrome P450 family 2 subfamily C member 8 (CYP2C8), cytochrome P450 family 2 subfamily C member 9 (CYP2C9), cytochrome P450 family 2 subfamily C member 19 (CYP2C19), cytochrome P450 family 2 subfamily D member 6 (CYP2D6), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), Organic Anion Transporting Polypeptide 1B1 (OATP1B1) or strong inhibitors or inducers of Cytochrome P450 3A4 (CYP3A4; e.g. cyclosporine, tacrolimus or sirolimus) * Subjects taking the following other drugs if they cannot be held (per the Medical Director Austin Stone, MD, PhD) for at least 2 days before and during administration of Fisetin: cyclosporine, tacrolimus, repaglinide, and bosentan * Significant liver disease (i.e. greater than or equal to 2x the upper limit of normal bilirubin levels) or as in the opinion of the Medical Director * Significant renal disease (estimated glomerular filtration rate (eGFR) of \<60 ml/min/1.73m2) or as in the opinion of the Medical Director * History of other formally diagnosed joint diseases including osteonecrosis, acromegaly, Paget's disease, Ehlers-Danlos Syndrome, Gaucher's disease, Cushing's syndrome, Stickler's syndrome, joint infection, hemophilia, hemochromatosis, or neuropathic arthropathy of any cause * Patients with type 1 or 2 diabetes (Hemoglobin A1c (HbA1c) \> 6.5%) and/or taking medications that affect insulin levels, including: Metformin (within the last week), Glucocorticoids (within the last month), Acarbose (within the last week)