Oxidative Stress Links Aging, Activity and Mobility Limitation

With the premise that U.S. Veteran demographics reveal an aging population with significant
mobility limitation and oxidative stress is tightly linked to both of these characteristics,
a series of skeletal muscle/vascular studies are proposed. Specifically, in a series of
recent studies the investigators' group has documented positive vascular consequences of
antioxidant supplementation during exercise in older subjects that negatively impacted young
people. Further provocative findings revealed that following exercise training the older
subjects were now also negatively impacted by the antioxidant supplementation. These
findings have implications for the understanding of the complex balance between the positive
effects of exercise-based rehabilitation, exercise induced oxidative stress, aging, frailty,
and subsequent mobility limitation. Therefore four specific aims are proposed that will
answer the questions of where (I) oxidative stress is most prevalent in the elderly, why
(II) oxidative stress occurs in the elderly, what (III) are the acute consequences of
oxidative stress in the elderly, and finally how (IV) can exercise-induced oxidative stress
as the result of exercise training in elderly be appropriately managed with exogenous
antioxidant therapy to promote compliance and the positive outcome of increased mobility.

Inclusion Criteria:

- Healthy men and women aged either between 18 - 30 years (young group) and >70 years
(old group)

- Free of overt disease. Subjects will be non-obese (BMI < 30) and have plasma glucose
concentrations < 7.0 mmol/L under fasting conditions and < 11.1 mmol/L at 120 minutes
of an oral glucose tolerance test (OGTT)

- Subjects will be sedentary, defined here as no regular physical activity for at least
the prior 2 years

- Candidates must have no orthopedic limitations that would prohibit them from
performing cycle or knee-extensor exercise

- All women will be postmenopausal (either natural or surgical) defined as a cessation
of menses for at least 2 years, and in women without a uterus, follicle stimulating
hormone (FSH) > 40 IU/L

Exclusion Criteria:

- Candidates demonstrating dyslipidemia based on the National Cholesterol Education
Program Guidelines of plasma total cholesterol > 240 mg/dl with LDL-cholesterol > 160
mg/dl will be excluded from participation

- Candidates who smoke or are taking medications (blood pressure medications, statins,
antioxidants etc.) that could influence the results of the study will not be eligible

- In terms of diet, subjects will be asked to maintain a dietary record for one week
prior to the pre-screening and if this reveals a diet that differs substantially from
the "typical" average diet in both the young and old, the subject will not be
eligible

- Women currently taking hormone replacement therapy (HRT) in the preceding year will
be excluded from the proposed studies