Measuring Protein Turnover in Humans Across the Lifespan by Metabolic Labeling With Deuterium Oxide

Healthy Volunteers Clinical Trial

Official title: Measuring Protein Turnover in Humans Across the Lifespan by Metabolic Labeling With Deuterium Oxide

Status Recruiting

Clinical Trial Summary

Background:

Proteins are essential to the health and structure of the cells that make up body tissues. Most proteins become damaged over time and are replaced with new ones. This process is called "protein turnover." Stress, disease, and aging can affect this process. Researchers want to better understand how aging affects protein turnover.

Objective:

To measure rates of protein turnover in healthy adults.

Eligibility:

Healthy people aged 20 years and older with a body mass index between 20 and 30.

Design:

Participants will have 6 study visits over 4 to 6 weeks. They will fast 12 hours before each visit.

Participants will be screened. They will have a physical exam, with blood and urine tests and tests of their heart function. They will lie down while blood pressure cuffs are used on their arms and legs.

Participants will be given bottles of heavy water to drink at home on a schedule for 21 days. Each bottle holds about 3.5 tablespoons. Heavy water is odorless, colorless, and tasteless, like normal drinking water. It is safe to drink and has been used in research for many years.

Participants will have tests during study visits, including:

Imaging scans of a leg.

Exercise on a treadmill.

Biopsies of muscle, skin, and fat: Small samples of tissue will be cut from the calf and abdomen.

Resting metabolic rate: Participants will lie still and breathe into a mask for 20 minutes.

Knee/grip strength: Participants will do strength tests with their legs. They will squeeze a device with their hands.

D3-Creatine: Participants will take 1 pill of D3-Creatine, which occurs naturally in muscle.

Clinical Trial Description

Study Description:

A sophisticated biological system of quality control ensures that proteins are maintained in all cells in the right absolute and relative quantities and their architectural characteristics are preserved so that they can perform their biological function. There is evidence from animal models that the half-life of a subset of proteins is longer with aging so that aggregated proteins are retained for longer time than in younger individuals, leading to reduced cellular function. On the other hand, other proteins such as mitochondrial proteins are damaged at a higher rate and are expected to turnover faster to maintain function. This study is aimed at evaluating the half-life of a range of proteins in muscle, peripheral blood mononucleated cells (PBMCs), and skin in participants of different ages and tests the hypothesis that for specific proteins, older persons have different protein turnover than younger persons and that the effect of aging on proteins half-life is also dependent on the specific tissue considered.

Objectives:

Primary Objective: To measure the turnover proteins in humans across tissues, age, and sex.

Secondary Objective: To test the hypothesis that older age is associated with diminished protein turnover.

Endpoints:

Primary Endpoint: The primary endpoint of this study is to characterize the turnover of different proteins in human tissues, including skeletal muscle, subcutaneous fat, skin and PMBCs.

Secondary Endpoint: The secondary endpoint of this study is to assess whether the turnover of proteins in different tissues is significantly associated with aging. In exploratory analyses we will also test the hypothesis that independent of age, the turnover of certain proteins is systematically different between different tissues. ;

Related Conditions & MeSH terms

• Healthy Volunteers

• NCT number: NCT06269653
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Linda M Zukley, Ph.D.
• Phone: (410) 350-3983
• Email: zukleylm@mail.nih.gov
• Status: Recruiting
• Start date: June 26, 2024
• Completion date: March 1, 2026