The purpose of this study is to assess the efficacy of supplementation with the Nicotinamide Adenine Dinucleotide (NAD+) precursor compound, Nicotinamide Riboside (NR), for improving physiological function (vascular, motor, and cognitive) in healthy middle-aged and older adults.

Overall, the proposed research project has the long-term potential to influence clinical practice by establishing novel therapies for treating multiple domains of age-associated physiological dysfunction and thereby reducing the risk of clinical disease and disability.

Inclusion Criteria:

• Ability to provide informed consent
• Baseline brachial flow-mediated dilation (FMD) < 6%Δ (rationale: non-invasive screening to ensure exclusion of subjects with exceptionally high baseline endothelial function.
• Ability to perform motor and cognitive tests (e.g., can rise from a chair, walk for 2 min, climb 10 stairs)
• Women will be confirmed as postmenopausal (either natural or surgical) based on cessation of menses for >1 year.

Exclusion Criteria:

• ages <55 years or ≥80 years
• body mass index (BMI) >40 kg/m2 (rationale: vascular function and blood pressure measurements can be inaccurate in severely obese subjects and these subjects may differ in many ways from normal weight, overweight or less obese subjects)
• not weight stable in the prior 3 months (>2 kg weight change) or unwilling to remain weight stable throughout study (rationale: recent weight change or weight loss can influence vascular function)
• having unstable angina, acute myocardial infarction, coronary angioplasty, or aorto-coronary bypass surgery as defined by the occurrence of an event, symptom, surgery, or change in medication and/or dosage within 3 months prior to enrollment
• having thyroid disease that is not controlled by medications or <3 month's use of a particular medication and/or dosage (rationale: uncontrolled thyroid diseases are associated with alterations in vascular function)
• having past or present alcohol dependence or abuse, as defined by the American Psychiatry Association, Diagnostic and Statistical Manual of Mental Disorders
• abnormal blood chemistries for renal and liver function (>1 standard deviation outside the normal range)
• Moderate or severe peripheral artery disease (ankle-brachial index <0.7).
• Insufficient health to participate in a VO2max test based on a physical examination and/or graded exercise test (this will be determined in accordance with stated contraindications for exercise testing provided by the American Heart Association).