Novel Methodology to Measure Protein Accumulation
| Status: | Completed |
|---|---|
| Conditions: | Healthy Studies |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 5/3/2014 |
| Start Date: | December 2011 |
| End Date: | July 2015 |
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.
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.
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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