Protein Digestion and Amino Acid Absorption in the Aging Gastrointestinal Tract

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