Novel Methodology to Measure Protein Accumulation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Isotopic enrichment of plasma and skeletal muscle proteins achieved by oral ingestion of [13C6]-phenylalanine
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 18-30 years
- •Age greater than 65 years
排除标准
- •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.
结局指标
主要结局
Isotopic enrichment of plasma and skeletal muscle proteins achieved by oral ingestion of [13C6]-phenylalanine
时间窗: 3 weeks
Administration of an oral amino acid mixture containing isotopically-labeled \[13C6\]-phenylalanine (13C-Phe) will result in 13C-Phe incorporation into newly synthesized proteins. Measuring isotopic enrichment (IE) of 13C-Phe immediately after administration and weekly for 3 consecutive weeks will allow for estimation of protein accumulation.
Degree of post-translational modifications in plasma and muscle proteins
时间窗: 3 weeks
The abundance of post-translational modifications of plasma and muscle proteins will be measured using mass spectrometry.
次要结局
- Assess differences in protein accumulation as a function of age(3 weeks)
- Assess differences in protein modification/damage as a function of age(3 weeks)
研究者
K. Sreekumaran Nair
Professor of Medicine
Mayo Clinic