Novel Methodology to Measure Protein Accumulation


Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

Accumulation of damaged proteins is thought to underlie many degenerative conditions, including aging, diabetes, Alzheimer's disease, cataracts, and others. Over time, proteins can be irreversibly damaged by a variety of factors, such as reactive oxygen species, and without timely degradation they can accumulate and aggregate. We believe this can contribute to the development of chronic degenerative disorders. The purpose of this study is to develop a novel methodology for measuring protein accumulation and test it in two groups of people: young (18-30 years) and old (≥65 years). This methodology will require that people drink a solution of essential amino acids that includes isotopically labeled L[ring-13C6]phenylalanine. We will then collect blood and muscle samples, to isolate plasma and skeletal muscle proteins. Participants will return to the study center four more times on a weekly interval. We hypothesize that older proteins, which persisted in circulation and accumulated over time, will have a higher degree of post-translational oxidative damage than newly synthesized proteins.

Who is eligible to participate?

Inclusion Criteria: - Age 18-30 years - Age greater than 65 years Exclusion Criteria: - Active or uncontrolled cardiovascular disease - Chronic kidney disease with serum creatinine ≥ 1.4 mg/dL for women and ≥ 1.5 mg/dL for men - Chronic liver disease (elevation in serum transaminases ≥ 3 times the upper limit of normal) - Any debilitating chronic illness, including malignancy - Significant malabsorptive state, including prior gastric bypass surgery or inflammatory bowel disease - Diabetes mellitus (types 1 or 2) or glucose ≥ 110 mg/dL. - Obesity (BMI ≥ 31 kg/m2) - Anticoagulant therapy (warfarin or heparin) or bleeding disorder that increases risk of bleeding during a muscle biopsy. - Anemia (hemoglobin ≤ 11 g/dL) - Use of medications known to modulate protein synthesis, mitochondrial function, and/or glucose homeostasis (including β-blockers and corticosteroids). - Participation in another study where the 13CPhe was administered during the past 6 months. - Moderate or high level of structured exercise (on average, ≥ 30 minutes per day and ≥ 2 days per week) - Pregnancy - Daily use of tobacco products (smoking or chewing); or smoking ≥7 cigarettes per week, on average. Abstinence from tobacco for ≥3 months is required before enrollment in the study.

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