Protein Digestion and Amino Acid Absorption in the Aging Gastrointestinal Tract
NCT Number: NCT06553794
Acronym: AgingGut
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Protein Malabsorption
Interventions: OTHER: Gastroscopy with duodenal mucosal tissue biopsies
Sponsor: Maastricht University Medical Center
Collaborators: FrieslandCampina
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 24
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: BASIC_SCIENCE
Start Date: 2024-08
Completion Date: 2025-03

Summary:
Rationale: Worldwide, the aging population is increasing. Aging is associated with loss of independence and increased risk of co-morbidity. Sufficient protein intake is imperative to maintain skeletal muscle mass and overall health, and thereby stimulates active aging. It has been suggested that age-dependent changes in gastrointestinal (GI) tract physiology affect the amount of protein digested and absorbed, as well as the intestinal microbiota. However, it is not clear to what extent actual protein digestion and absorption are altered in older individuals. So far, no human data on the expression and activity of brush border enzymes and protein-related transporters in small intestinal epithelial cells are available. Understanding the age-dependent digestion and absorption kinetics of protein is important for creating specific diets in older individuals to improve protein intake and thereby stimulate healthy aging.

Objective: To assess the effects of aging on protein digestion and amino acid absorption in healthy humans in vivo.

Study design: Cross-sectional Study population: 12 healthy, non-obese (BMI 18.5-30kg/m2) young adults (age: 18-35 y inclusive) and 12 community dwelling older adults (age: ≥67 y).

Intervention: Subjects will undergo a standardized heavy water dosing protocol for 2 days (1 "loading day", 1 "maintenance day"). Blood and saliva sampling will be conducted throughout the heavy water dosing protocol to determine body water and amino acid enrichment levels. On the experimental test day, a gastroscopy with collection of duodenal mucosa tissue samples will be performed to allow assessment of the expression and activity of brush border enzymes and protein-related transporters, and to determine fractional duodenal mucosal protein synthesis rate. Fecal samples will be collected at baseline and after the gastroscopy.

Main study parameters/endpoints: The primary study parameter is the mRNA expression of brush border enzymes and small peptide and amino acid transporters in duodenal mucosal cells. Secondary study parameters include protein expression of brush border enzymes and small peptide and amino acid transporters in duodenal mucosal cells, fecal microbial fermentation metabolites and duodenal mucosal protein synthesis rate.

Primary Outcome Measures: Gene expression of brush border enzymes and protein-related transporters in duodenal mucosal cells, as determined by real-time polymerase chain reaction (PCR), day 3 of study period
Secondary Outcome Measures: Protein expression of brush border enzymes and protein-related transporters, as determined by proteomic analysis, day 3 of study period|Microbial proteolytic fermentation metabolites involved in protein metabolism, as determined by high performance liquid chromatography-mass spectrometry, Baseline|Fractional duodenal mucosal protein synthetic rate, as determined using stable isotope tracer methodology (D2O), during study period (3 days)|Fecal elastase, as marker for pancreatic enzyme secretion, Baseline|Plasma citrulline, as a marker for total functional enterocyte mass, Baseline
Other Outcome Measures: Age in years, Reported by participants, Baseline|Body weight in kg, Scale, Baseline|Height in m, Stadiometer, Baseline|BMI in kg/m2, Calculated based on height and weight, Baseline|Blood pressure in mmHg, Electrical sphygmomanometer, Baseline