Ignite Creation Date:
2024-10-26 @ 3:37 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06553794
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2023-06-27
Brief Title:
Protein Digestion and Amino Acid Absorption in the Aging Gastrointestinal Tract
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Protein Digestion and Amino Acid Absorption in the Aging Gastrointestinal Tract
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
AgingGut
Brief 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 185-30kgm2 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 parametersendpoints 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
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 185-30kgm2 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 parametersendpoints 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
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 andor 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 ie 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
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 ie 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None