Skeletal Muscle Apoptosis and Physical Performance; Oxidative RNA/DNA Damage and Repair in Aged Human Muscle
Completed
Conditions studied: Sarcopenia
In brief
The age-related loss of muscle mass and strength, also termed sarcopenia, is a commonly recognized consequence of aging and has been associated with frailty, functional loss, hospitalization, and increased mortality among older people. Sarcopenia and its consequences have a considerable economic impact, since it has been estimated that the healthcare cost attributable to sarcopenia in the US in 2000 was $ 18.5 billions. Preclinical animal models strongly suggest that apoptosis, a programmed cell death, might play a prominent role in the age-related muscle wasting. In specific aim one, the investigators will assess the extent of muscle apoptosis in muscle biopsies obtained from the vastus lateralis muscle of young control subjects (ages 20-35) and high-performance and low-performance older subjects (age range 70-99 years). In specific aim 2, the investigators will investigate the role of Poly (ADP-ribose) polymerase 1 (PARP-1) and apoptosis-inducing factor (AIF) in the induction of skeletal muscle apoptosis. In specific aim 3, the investigators propose to investigate the contribution of the muscle energy deficit, due to the age-related mitochondrial dysfunction, in the development of muscle wasting. Finally, in specific aim 4, the investigators propose to reassess after four years physical performance, muscle mass and the extent of muscle apoptosis, in the high-performing participants, in order to correlate eventual decline in physical function, muscle mass and functional status, with changes in muscle apoptosis and in biochemical parameters in this very old population. Physical performance will be established according to the summary performance score obtained in the Short Form Physical Performance Battery (SPPB). In addition to the SPPB the investigators will also employ hand grip strength and knee extensor strength tests and the investigators will quantify muscle contractile area using 3D magnetic resonance imaging. Disability will be assessed using a self-report questionnaire. These studies will enhance our understanding of the biology and pathophysiology underlying the geriatric syndrome of sarcopenia and provide significant and novel insights that will enable us to identify new potential targets for interventions aimed at preventing and treating sarcopenia and functional impairment in older adults.
Key facts
- Study ID
- NCT01644279
- Run by
- University of Florida
- People needed
- 63
- Starts
- 2006-03-01
- Expected to finish
- 2016-07-01
- Last updated by the study team
- 2016-11-03
Who can join
Age: 20 and older. Sex: any. Healthy volunteers: accepted.
You may not qualify if…
- history of smoking in the prior 12 months
- active treatment for cancer or history of cancer in the past 3 years
- congestive heart failure New York Heart Association (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., Mini-Mental State Examination (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 growth hormone (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:
Where it is running
- University of Florida — Gainesville, Florida, United States
Full record on ClinicalTrials.gov
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