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.
Study Type
OBSERVATIONAL
Enrollment
24
Oral drink composed of essential amino acids including L\[ring-13C6\]phenylalanine
Mayo Clinic
Rochester, Minnesota, United States
Isotopic enrichment of plasma and skeletal muscle proteins achieved by oral ingestion of [13C6]-phenylalanine
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.
Time frame: 3 weeks
Degree of post-translational modifications in plasma and muscle proteins
The abundance of post-translational modifications of plasma and muscle proteins will be measured using mass spectrometry.
Time frame: 3 weeks
Assess differences in protein accumulation as a function of age
Use the newly developed methodology to assess whether otherwise healthy older adults (≥65 years old) have greater accumulation of plasma and muscle proteins compared to healthy young adults (18-30 years old).
Time frame: 3 weeks
Assess differences in protein modification/damage as a function of age
The abundance of post-translational modification/damage of plasma and muscle proteins will be measured using mass spectrometry in young (18-30 years old)and older (\>65 years old) adults.
Time frame: 3 weeks
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