Skeletal Muscle Apoptosis and Physical Performance; Oxidative RNA/DNA Damage and Repair in Aged Human Muscle

Young (age 20-35 years; N =20), old high-functioning, (age 70-99 years; N = 25), and old low-functioning (age 70-99 years; N = 20) subjects.

Inclusion criteria. The following inclusion criteria will be adopted to select the study participants:

• males and females aged 20-35 and 70-99 years
• sedentary lifestyle (i.e., the subject has spent less than 20 minutes per week in the past 2 month performing structured physical activity, such as exercising at a gym and/or weight training)
• willing and able to give informed consent.

Exclusion criteria:

• history of smoking in the prior 12 months
• active treatment for cancer or history of cancer in the past 3 years
• congestive heart failure NYHA Class III or IV
• previous stroke with upper and/or lower extremities involvement within the last 6 months
• peripheral vascular disease Fontaine Class III/IV
• History of life-threatening cardiac arrhythmias, stroke, severe Parkinson's disease or severe neurological disorders likely to interfere with physical function
• cognitive impairment (i.e., MMSE ≤ 23)
• renal disease requiring dialysis
• lung disease requiring steroids
• lower extremity amputation
• severe osteoarthritis that interferes with physical function
• Complicated diabetes
• inflammatory diseases such as active rheumatoid arthritis, vasculitis, autoimmune disorders, and inflammatory bowel disease
• life-threatening illnesses with an estimated life expectancy less than 1 year
• history of drug or alcohol abuse
• taking GH and/or estrogen replacement therapy
• Testosterone medication
• Anticoagulant therapy
• involved in active weight loss > 5 kg in prior 3 months
• planning to relocate out of the study area in the next 4 years (ages 70-99 only)
• pregnancy
• SPPB score of 8-10
• Lidocaine allergy
• MRI exclusions, such as pregnancy, claustrophobia, heart pacemaker / defibrillator, heart valve prosthesis, aneurysm clip, metallic stent, neurostimulation system, cochlear implants or inner ear prosthesis, insulin pump or other infusion pump, metal slivers in the orbital area/eye socket

Temporary exclusion criteria:

• recent bacterial infection (< 2 weeks)
• acute febrile illness in prior 2 months
• high blood pressure (i.e., BP ≥ 180/110 mm Hg) at the screening visit (subject will be referred to his/her physician and reevaluated after appropriated therapy being instituted)
• major surgery or hip/knee replacement in the past 6 months

Assessment of disability. The uniform measure proposed to use for the assessment of disability will be a self-report disability questionnaire. This questionnaire was developed for the Fitness Arthritis in Seniors Trial (FAST) and since then has been widely used in intervention and observational studies (e.g. ADAPT, REACT-1, OASIS, CHAMP). The questionnaire is not specific to a certain disease and asks about perceived difficulties in general activities of daily living during the last month. Respondents answer for each of the items whether they experience 1) no difficulty, 2) a little difficulty, 3) some difficulty, 4) a lot of difficulty, 5) unable to do or, 6) did not do for other reasons. Answers can be averaged across the items in order to receive an indication of the overall perceived disability burden by a person.