Table 2 Study inclusion and exclusion criteria

Inclusion criteria

• ≥65 years of age

• Independently mobile with an SPPB score 4–12

• Access to transportation

• Capable of providing informed consent (cognitively intact)

• Negative diagnostic (12-lead ECG), submaximal Graded Exercise Testing (GXT) (if applicable)

Exclusion criteria

• Obesity (body mass index (BMI) >30)

• Serum creatinine >1.4 because of risk of lactic acidosis with metformin

• History of structured, regular resistance exercise training within the past year (more than two times per week consistently)

• Chronic aspirin or non-steroidal anti-inflammatory drug (NSAID) use (unless it can be safely stopped prior to the biopsies) and any other use of an anticoagulant (e.g., Coumadin) or history of bleeding

• History of alcoholism or liver disease

• History of hypo- or hypercoagulation disorders including subjects taking Coumadin

• Any end-stage disease and/or a life expectancy less than 1 year

• Neurological, musculoskeletal, or other disorder that would preclude them from completing resistance training and all performance tests

• Uncontrolled hypertension, unstable or exercise-induced angina pectoris or myocardial ischemia, or congestive heart failure

• Diabetes mellitus: HgbA1C >6.5, or fasting glucose >126 mg/dl, or 2-h glucose (on oral glucose tolerance test (OGTT)) >200)

• Any other medical condition that would interfere with testing or increase one's risk of complications during exercise, as judged by the study physicians

• Any other condition or events considered exclusionary by the Principal Investigator and/or physician, such as non-compliance

• Lidocaine allergy (1% lidocaine is the local anesthetic used during the muscle biopsy procedure)

• Currently receiving androgen or anabolic therapy