Inclusion Criteria
The new IDF's 2006 consensus worldwide definition for MetS will be followed for inclusion. MetS will be defined as having central obesity with ethnicity-specific values, plus two or more of the following criteria: Hypertension, dyslipidemia, or hyperglycemia. Hypertension is defined by the use of antihypertensive medication and/or blood pressure of ≥130/85 mmHg. Dyslipidemia is defined as blood triglycerides \>150mg/dL or high-density lipoprotein (HDL) \< 50mg/dL, or specific treatment for either lipid abnormality. Hyperglycemia is defined as a fasting glucose ≥100mg/dL. Inclusion criteria for LUTS are having urgency with or without other urinary symptoms for at least 3 months, with a score of 1 or 2 on the Urgency Perception Scale questionnaire 60 , and a total score of at least 6 on the OABSS questionnaire (with at least a score of 2 on the third OABSS question "How often do you have a sudden desire to urinate, which is difficult to defer?").
* Women 50years or older with metabolic syndrome and LUTS as defined above.
* Speak, read and understand English
* Willingness to provide consent and participate in all aspects of the trial including randomization to the intervention group
Exclusion Criteria
The exclusion criteria for Mito-LUTS include conditions that will interfere with our research questions, including advanced co-morbidities and immunological disorders. They are as follows:
* Frailty, defined as meeting 3 of 5 frailty indicators of the Fried Frailty Phenotype
* History of severe renal impairment and/or eGFR ≤ 60 mL/min/1.73m2 at the study physician's discretion
* Excessive alcohol use (more than 14 alcoholic drinks/week)
* Clinical/laboratory evidence of hepatic disease (via medical history and/or AST and/or ALT ≥ 3 times upper limit of normal at screening)
* Poorly Controlled Diabetes
* Unwilling or unable (due to significant cognitive impairment) to provide informed consent.
* Terminal illness with life expectancy less than 12 months
* Advanced neurological disorder (Alzheimer's, Parkinson's, ALS, MS, dementia, seizures)
* A score of 30 or less on the modified Telephone Screening of Cognitive Status administered during the in-person screening visit.
* Cancer or history of gynecological cancer or history of cancer requiring chemotherapy or radiation.
* A history of gastric ulcers.
* Abnormal findings on endoscopy.
* Recent (within the last 2 weeks) or current chronic use of NSAIDs or other drugs or agents with the potential for gastric mucosal toxicity (except for daily use of baby aspirin or famotidine for which participants will not be excluded). Sporadic use of NSAIDs will not be an exclusion criterion.
* Significant co-morbid disease (severe chronic obstructive pulmonary disease, active rheumatologic diseases, chronic infection (HIV, tuberculosis), severe congestive heart failure (NYHA class 4), myocarditis, etc)
* Myocardial infarction, stroke or hospitalization for heart failure in the last 12 months
* QTc \>460 ms at screening on ECG
* Prior diagnosis of ventricular arrhythmia (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
* Severe active psychiatric disorder (e.g. bipolar, schizophrenia)
* Unable to complete physical performance testing due to medical conditions (at discretion of the PI)
* Unintentional weight loss \>15 lbs in past 12 months
* Immunosuppressive disorders or taking immunosuppressive medications (including oral prednisone \> 10mg/day)
* Sub-cerebellar lesions
* Subjects must not be on warfarin or other blood thinning medications or have a known bleeding disorder.
* Conditions that might interfere with clinical diagnosis (such as pelvic organ prolapse ≥ stage 2, pelvic radiotherapy, any concurrent condition that could cause incontinence, hematuria, vaginitis, neurogenic lower urinary tract dysfunction); chronic pelvic pain syndrome, interstitial cystitis/bladder pain syndrome, pelvic malignancy, active urinary tract infection (UTI), recent urologic procedure (\<6 months).
* Clean intermittent catheterization or indwelling catheter
* Current participation in another interventional study
* Pregnancy and nursing
* Subjects must not have used antibiotics for at least 3 weeks prior to visit 1, received a vaccination in the 2 weeks prior to visit 1 or used medicine that alters the immune response (eg high dose corticosteroids) in the 6 months prior to visit 1. Subjects must not have had an acute infection in the 3 weeks prior to visit 1 or had a major severe illness or been hospitalized in the 3 months prior to visit 1. If participants are within any of these windows when they are screened, they will be scheduled for a screening visit but will only be invited for Visit 1 after these specified windows have elapsed and/or infections have resolved.
* Subjects must not be on or have taken any of the following anti-muscarinics or β3- adrenoreceptor agonists for 3 weeks prior to visit 1: o Darifenacin (enablex), Oxybutynin (ditropan), Solifenacin (vesicare), Fesoterodine (Toviaz), Tolterodine (detrol), Trospium (sanctura), Imipramine (tofranil), Mirabegron (myrbetriq), Vibegron (gemtesa)
