Resveratrol to Enhance Vitality and Vigor in Elders

Resveratrol, a compound found in red wine and dark-skinned grapes, will improve the function of mitochondria (energy producing components) within the leg muscles of moderate functioning older adults.

The investigators will look at the role Resveratrol plays in improving physical function by studying the connection of changes in mitochondrial function and changes in physical function.

An initial telephone screening indicated that the subject may be eligible to participate in the study. The first study visit ("Screening visit") will further determine if the subject is eligible to participate. Should the subject be eligible to participate in the study, the subject will be asked to participate in a daily resveratrol or placebo supplementation program for approximately 90 days. The subject will also be asked to return to the clinic for two additional assessment visits to monitor his/her safety and measure study results.

Details regarding the tests to be conducted during this screening visit and other study visits are described below. Visits will take place at the University of Florida Institute on Aging (IOA).

The Screening Visit is approximately 1.5 to 2 hours and will include:

1. Blood Draw: The subject is asked to fast before the appointment because blood will be collected during this visit. The investigator will collect approximately 2 tablespoons of blood. The purpose of this blood draw is to determine levels of certain compounds in the subject's blood that will help determine eligibility.
2. Questionnaires: The subject will be asked questions about medical history and medications as well as mood and will also be asked to complete a short test of memory and reasoning.
3. Physical Measurements: measurements of the subject's height, body weight, waist circumference, pulse, and blood pressure.
4. Physical Exam: A licensed health care provider will perform a brief physical exam to determine if it is safe to continue with the study. This exam will include a review of medical history, medications, and measurement of height, blood pressure, radial pulse, weight, and waist circumference.
5. Tests of physical performance: The subject will be asked to complete tests of physical ability that include:

   1. Walking at the usual pace for a distance of 13 feet (4 meters) two (2) separate times
   2. The subject will be asked to go from a standing to a sitting position, without using their arms. If the subject is able to perform this task, then they will be asked to stand up from and sit down on chair five (5) times as fast as possible.
   3. Maintaining balance while standing in three (3) different positions

Baseline Visit 1: Should the subject be eligible for the study, they will be asked to return to the clinic for the first baseline study visit. This visit is expected to take 2 to 3 hours and will include:

1. Measurement of pulse and blood pressure
2. Measurement of body weight and waist circumference
3. Collection of fasting blood samples
4. Questions about the subject's health
5. Tests of physical performance, including:

   1. Walking as fast and far as the subject can for 6 minutes
   2. Walking at subject's usual pace for a distance of 13 feet (4 meters) two (2) separate times
   3. Standing from a sitting position, without using their arms. If the subject is able to perform this task, then they will be asked to stand up from and sit down on chair five (5) times as fast as possible.
   4. Maintaining balance while standing in three (3) different positions.
   5. Assessment of lower-body muscle strength and endurance
6. Physical Activity Monitor: The subject will also be asked to wear an armband physical activity monitor during a typical seven day period to assess baseline physical activity habits. The monitor will be returned at Baseline Visit 2.

Baseline Visit 2 will take approximately 2 hours and will include:

1. Measurement of pulse and blood pressure before procedure
2. Muscle Tissue Sample: The procedure to collect muscle samples will be performed by a licensed healthcare provider with experience conducting the procedure. The procedure includes numbing a small area on the thigh with a local anesthetic and then using a needle about the size of a pen to collect a small amount of muscle tissue approximately equal to the size of the head of a pencil eraser.

   After the tissue sample is taken, the subject will receive detailed instruction on how to care for the incision site. Several follow-up phone assessments will be made inquiring about any problems that the subject may be experiencing related to the procedure.
3. Measurement of pulse and blood pressure after procedure
4. Randomization: Subjects who are eligible and safe to continue with the study, will be randomly assigned to one of three conditions: (1) resveratrol (1000 mg/day) (2) resveratrol (1500 mg/day) or (3) placebo (vegetable cellulose).
5. The subject will be provided with a supply of the study drug capsules of at least 30 days and will be asked to return any remaining study drug capsules to the clinic at the next appointment. Subjects will be asked to orally consume one study drug capsule following each main meal (i.e. breakfast, lunch and dinner) with a glass of water.

30-Day \& 60-Day Visits last approximately 1 hour and include:

1. Collection of fasting blood samples
2. Measurement of pulse and blood pressure
3. Measurement of weight and waist circumference
4. Update medical history and ask questions about any adverse experiences the subject may have had since the last visit
5. Counting of any remaining study drug capsules that were not taken since last visit
6. Providing the subject with study drug capsules needed until the next study visit

90-Day Visit 1 is similar to the Baseline 1 visit and will last approximately 2-3 hours. This visit includes:

1. Measurement of pulse and blood pressure
2. Measurement of body weight and waist circumference
3. Collection of fasting blood samples
4. Update medical history and ask questions about any adverse experiences the subject may have had since last visit
5. Counting of any remaining study drug capsules that were not taken since last visit
6. Tests of physical performance, including:

   1. Walking as fast and far as possible for 6 minutes
   2. Walking at usual pace for a distance of 13 feet (4 meters) two (2) separate times
   3. Standing from a sitting position, without using arms. If the subject is able to perform this task, he/she will be to stand up from and sit down on chair five (5) times as fast as possible.
   4. Maintaining balance while standing in three (3) different positions.
   5. Assessment of lower-body muscle strength and endurance
7. The subject will receive an armband physical activity monitor to wear for seven days, and will be asked to return this monitor at the 90-Day Visit 2.

90-Day Visit 2 will be similar to the Baseline 2 visit and will last approximately 1.5 to 2 hours.

1. Procedure to collect muscle tissue sample (as described in Baseline 2)
2. Counting of any remaining study drug capsules that were not taken since last visit.

Follow-Up 10-Day \& 30-Day Visits are approximately 30 minutes to 1 hour

1. Measurement of pulse and blood pressure
2. Collection of fasting blood samples
3. Update medical history and ask questions about any adverse experiences the subject may have had since last visit

Eligibility Criteria:
Inclusion Criteria:

* Ability to understand study procedures and to comply with them for the entire length of the study;
* Age 65 years and older;
* Moderate to high functioning (i.e. a summary score of 4 - 10 on the Short Physical Performance Battery \[SPPB\]);
* Body Mass Index (BMI) range: 20-39.9 kg/m2;
* Willingness to undergo all testing procedures.

Exclusion Criteria:

* Failure to provide informed consent;
* Allergy/sensitivity to grapes or Japanese knotweed;
* Current dietary supplementation of grape seed extract or ginko biloba;
* Consumption of ≥ 8 oz. of red wine/dealcoholized red wine/red or purple grape juice more than once weekly;
* Consumption of any dietary supplements containing resveratrol, quercetin, or P. cuspidatum in the previous 90 days;
* Active treatment for cancer, stroke (\< 6 months), peripheral vascular disease, coronary artery disease, myocardial infarction (\< 6 months), congestive heart failure (stage III or IV), valvular heart disease, major psychiatric disease, severe anemia (blood levels of Hemoglobin \< 8 g/dl), liver or renal disease, diabetes, severe osteoarthritis, blindness or deafness, fracture in upper or lower extremity ( \< 6 months), upper or lower extremity amputation, or Parkinson's disease;
* Cognitive impairment (i.e. Mini Mental Status Exam ≤ 23);
* History of significant head injury;
* Physical activity (i.e. running, bicycling, etc.) ≥ 120 min/week;
* Excessive alcohol use (\> 2 drinks/day) or alcohol abuse (\> 5 drinks/day for males, or \> 4 drinks/day for females);
* History of substance abuse within the past six months;
* Mood disorder (i.e. Center for Epidemiological Studies - Depression (CES-D) ≥ 16);
* History of tobacco use within the past three years;
* Resting heart rate \> 120 bpm at screening visit;
* Systolic blood pressure \> 160 mm Hg at screening visit;
* Diastolic blood pressure \> 90 mm Hg at screening visit;
* Fasting glucose ≥ 126 mg/dL at screening visit;
* Abnormalities in blood chemistry parameters, defined by blood chemistry marker outside of healthy range);
* Current use of anabolic treatments (e.g. growth hormone or testosterone), anticholinesterase inhibitor (e.g. Aricept), hormone replacement (e.g. Estrogen), or anticoagulant therapies (note: aspirin use (≤ 81mg/day) is permitted);
* Participation in another clinical trial, or has received an investigational product within 30 days prior to screening/enrollment;
* Refuse to refrain from CoQ10 or alpha-lipoic acid while enrolled in the study.

Temporary Exclusion Criteria

* Recent bacterial/viral infection (\< 2 weeks);
* Acute febrile illness in past 2 months;
* High blood pressure (i.e. ≥ 140/90 mm Hg but ≤ 160/90) at the screening visit;
* Major surgery or hip/knee replacement (\< 6 months).