Protein Digestion and Amino Acid Absorption in the Aging Gastrointestinal Tract (AgingGut)

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.

Study Overview

• Status: Completed
• Conditions: Protein Malabsorption
• Intervention / Treatment: Other: Gastroscopy with duodenal mucosal tissue biopsies

Detailed Description

Worldwide, the proportion of older individuals in the population is increasing. The progressive loss of skeletal muscle mass with aging, or sarcopenia, has a major impact on our health care system and costs due to increased morbidity and a greater need for hospitalization and/or institutionalization. A sufficient protein intake is imperative to maintain skeletal muscle mass and overall health, and thereby stimulates active aging. Whereas the overall protein intake is generally lower in older as compared to young adults, findings indicate that older adults need more protein to increase muscle protein synthesis, known as anabolic resistance. The exact mechanisms underlying anabolic resistance are not fully discovered yet. Age-dependent changes in gastrointestinal tract physiology have been suggested as a potential cause.

Following protein ingestion, protein is cleaved into small peptides and amino acids by digestive enzymes secreted in the stomach (pepsin) and small intestinal lumen (pancreatic trypsin, chymotrypsin, elastase), as well as brush border enzymes (aminopeptidase, carboxypeptidase, dipeptidase). Brush border enzymes are responsible for the final digestion of small peptides into dipeptides, tripeptides and amino acids. Subsequently, these small peptides and amino acids are absorbed across the intestinal mucosa by various membrane-bound transporters. The majority of dietary-protein derived amino acids is released into the systemic circulation and transported and taken up by various peripheral tissues in the postprandial phase.

It has been shown that postprandial plasma amino acid availability is lower in older compared to young adults. This indicates that digestion and absorption of proteins are likely attenuated in older individuals, thereby reducing the systemic availability of protein-derived amino acids for muscle protein synthesis and other relevant physiological processes.

Limited studies have focused on changes in gastrointestinal tract physiology with aging. Human studies on the expression and activity of brush border enzymes and protein transporters (i.e. for dipeptides, tripeptides and amino acids) being crucial for the final steps of digestion and absorption, respectively, are lacking. Therefore, the aim of the present study is to assess the expression and activity of brush border enzymes and expression of protein transporters in small intestinal epithelial cells in older as compared to young adults.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht
    • Maastricht, Maastricht, Netherlands
      • Maastricht University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged 18-35 years or 67+ years
• Body mass index (BMI) between 18.5 and 30 kg/m2
• Regular stool frequency ranging from 1-3 times/day

Exclusion Criteria:

• History of cardiovascular, respiratory, gastrointestinal, urogenital, neurological, psychiatric, dermatologic, musculoskeletal, metabolic, endocrine, haematological, immunologic disorders, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol, interfere with the execution of the experiment, or potential influence the study outcomes (to be decided by the principal investigator and responsible physician)
• Major abdominal surgery interfering with gastrointestinal function (upon judgement of the principal investigator and responsible physician)
• Use of medication which limit participation in or completion of the study protocol, interferes with the execution of the experiment, or potential influences the study outcomes (to be decided by the principal investigator and responsible physician)
• Use of supplementation (i.e. protein, vitamin, pre- and probiotic supplementation) within 14 days prior to testing
• Administration of investigational drugs or participation in any scientific intervention study prior or during the study, which may interfere with this study (upon judgement of the principal investigator and responsible physician) Specific diet (e.g. vegetarian, vegan, gluten free, no diary) within the study period
• Planning to lose weight during the study period
• Excessive alcohol consumption (defined as > 14 alcoholic consumptions per week)
• Smoking
• Drug use
• Pregnancy
• Lactation
• Donated blood three months prior to the test day
• No given permission to register participation in electronic patient file at MUMC+ and to add records of gastroduodenoscopy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non-therapeutic intervention; Subjects will undergo a standardized heavy water dosing protocol for 2 days (1 "loading day", 1 "maintenance day") and consume a standardized diet for 2 days. On the experimental test day, a gastroscopy with collection of duodenal mucosa tissue samples will be performed.	Other: Gastroscopy with duodenal mucosal tissue biopsies; Subjects will undergo a standardized heavy water dosing protocol for 2 days (1 "loading day", 1 "maintenance day") and consume a standardized diet for 2 days. On the experimental test day, a gastroscopy with collection of duodenal mucosa tissue samples will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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

Outcome Measure	Measure Description	Time Frame
Age in years	Reported by participants	Baseline
Height in m	Stadiometer	Baseline
Body weight in kg	Scale	Baseline
BMI in kg/m2	Calculated based on height and weight	Baseline
Blood pressure in mmHg	Electrical sphygmomanometer	Baseline

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: FrieslandCampina
• Investigators: Principal Investigator: Luc van Loon, Prof, Maastricht University Medical Center; Principal Investigator: Daisy Jonkers, Prof, Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2024
• Primary Completion (Actual): June 13, 2025
• Study Completion (Actual): June 13, 2025

Study Registration Dates

• First Submitted: June 27, 2023
• First Submitted That Met QC Criteria: August 13, 2024
• First Posted (Actual): August 14, 2024

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Aging; Protein; Absorption; Intestinal mucosa; Digestion
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Diagnostic Techniques, Surgical; Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Endoscopy; Digestive System Surgical Procedures; Gastroscopy
• Other Study ID Numbers: METC23-029

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No