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AGING INDUCES HISTOLOGICAL CHANGES IN THE INTESTINAL MUCOSA THAT MAY REDUCE THE RESPONSE TO NUTRITIONAL SUPPORT

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AGING INDUCES HISTOLOGICAL CHANGES IN THE INTESTINAL MUCOSA THAT MAY REDUCE THE RESPONSE TO NUTRITIONAL SUPPORT

Francisco Vara-Luiz 1, Ivo Mendes 1, Carolina Palma 1, Margarida Rajão Saraiva 2, Ana Elisa Teles 3, Filipe Nogueira 3, Inês Costa Santos 3, Gonçalo Nunes 4, Marta Patita 3, Irina Mocanu 3, Sara Isabel Ramos Pires 3, Tania Meira 3, Ana Isabel Vieira 3, Unknown Unknown 3, Daniel Gomes-Pinto 3, Paulo Mascarenhas 5, Jorge Fonseca 1

Affiliations

1 Hospital Garcia de Orta, Almada, Portugal|||Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health and Science, Almada, Portugal

2 Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

3 Hospital Garcia de Orta, Almada, Portugal

4 Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health and Science, Almada, Portugal|||Hospital Garcia de Orta, Almada, Portugal

5 Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health and Science, Almada, Portugal

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Abstract

Introduction

There is a widespread agreement that age is a significant predictor of impaired response to nutritional support. For the same amount of protein and energy provided, the increase in weight and fat-free mass is significantly lower in older persons. This is generally attributed to anabolic resistance, and impaired absorption is usually considered non-existent/irrelevant. Nevertheless, in older rats gradual changes of the intestinal mucosa were observed, including reductions in villus height/width and density, which reduce absorption. Despite this, the aging influence on human intestinal mucosa is a matter of debate, and the lack of knowledge is partially explained by the exclusion criteria of older patients from most research protocols.

Aims & Methods

We aimed to evaluate potential histological and ultrastructural changes associated with aging that may reflect reduced absorption in older people.
The present single-center study is observational and prospective. Younger (18-45 years) and older (≥70 years) adults referred for upper endoscopy for reasons unrelated with intestinal alterations were included and underwent duodenal biopsies. Those biopsies were analyzed for histological, histomorphometric and ultrastructural changes. Histologic analysis was performed using optical microscopy with hematoxylin–eosin staining observed by two pathologists, including one expert gastrointestinal pathologist. All samples were analyzed for the presence of mucosal atrophy according to the adapted Marsh–Oberhuber classification and histomorphometric evaluation of duodenal villi length in micrometers, with at least two villi being measured through the use of an automatic scale. For transmission electron microscopy, duodenal fragments were fixed in 3% glutaraldehyde in cacodylate buffer (0.1 M, pH 7.4) overnight at 4 °C. The fixed fragments were rinsed and post-fixed in 1.0% osmium tetroxide for 1 h in the same buffer and dehydrated in graded ethanol passages. The fragments were embedded in a mixture of Epon and Araldite after two 15-min passages in propylene oxide. Thin sections, cut on a ultramicrotome with a diamond knife, were stained on the grid with uranyl acetate and lead citrate and examined with a electron microscope.

Results

A total of 84 patients were included (38 men/46 women), 33 with 18-45 years and 50 with ≥70 years. There were no duodenal endoscopic or microscopic changes apart from mucosal atrophy that was evident in one older adult. The median villi length was 0.35 mm (0.23-0.43 mm) in older persons, lower than in younger adults (0.65 mm; 0.37-0.79 mm) (p<0.01). On ultrastructural evaluation, the enterocytes of older group showed several changes suggesting compromise of the normal cell physiology. These changes were not observed in younger adults, who displayed normal cell architecture with regular microvilli structure and normal organelles.

Variables		18-45 years (n=34)	≥ 70 years (n=50)
Age		34.8 ± 8.2 years	76.2 ± 4.1 years
Gender	Male	16 (47.1%)	22 (44.0%)
Gender	Female	18 (52.9%)	28 (56.0%)
Indication for upper endoscopy		Dyspepsia: 16 (47.1%) Gastroesophageal reflux disease 4 (12.1%) Peptic ulcer disease: 6 (18.2%) Dysphagia: 3 (9.1%) Radiological findings: 3 (9.1%) Iron deficiency anemia: 2 (6.1%)	Dyspepsia: 13 (26.0%) Gastroesophageal reflux disease: 11 (22.0%) Peptic ulcer disease: 10 (20.0%) Dysphagia: 4 (8.0%) Gastric antral vascular ectasia: 6 (12.0%) Gastric polyp: 4 (8.0%) Iron deficiency anemia: 1 (2%) Radiological findings: 1 (2%)
Duodenal histology	Normal	34 (100%)	49 (98.0%)
Duodenal histology	Marsh 3A	0 (0.0%)	1 (2%)
Duodenal villi length		0.57 ± 0.1 mm	0.35 ± 0.06 mm

Conclusion

Aging is associated with histological, histomorphometric and ultrastructural changes in the intestinal mucosa that can be linked with reduced absorptive capacity. Besides anabolic resistance, this could be a reason for the reduced response to nutritional support found in older citizens.

References

Soenen S, Rayner CK, Jones KL, et al. The ageing gastrointestinal tract. Curr Opin Clin Nutr Metab Care. 2016 Jan;19(1):12-8.
Patel BA, Patel N, Fidalgo S, et al. Impaired colonic motility and reduction in tachykinin signalling in the aged mouse. Exp Gerontol 2014; 53:24 – 30.
Saffrey MJ. Aging of the mammalian gastrointestinal tract: a complex organ system. Age 2014; 36:9603.
Ren WY, Wu KF, Li X, et al. Age-related changes in small intestinal mucosa epithelium architecture and epithelial tight junction in rat models. Aging Clin Exp Res 2014; 26:183 – 191.
Thomson AB. Small intestinal disorders in the elderly. Best Pract Res Clin Gastroenterol. 2009;23(6):861-74.
Nalapareddy K, Zheng Y, Geiger H. Aging of intestinal stem cells. Stem Cell Reports. 2022 Apr 12;17(4):734-740.

Event

UEG Week Berlin 2025

Topics

Gut Microbiota Small Intestine & Nutrition

Submission format

Abstract

Session

The gut ecosystem: From pathogenesis to treatment

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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	[ALL]	Experimental	Control	p
	N=529	N=264	N=265
Hospital admission due to infection	14 (2.65%)	7 (2.65%)	7 (2.64%)	1.000
Need for antibiotic treatment	8 (1.51%)	3 (1.14%)	5 (1.89%)	0.715
COVID-19	5 (0.95%)	4 (1.52%)	1 (0.38%)	0.218
Long-term complication	16 (3.02%)	4 (1.52%)	12 (4.53%)	0.077
Long-term unplanned surgery	11 (2.08%)	1 (0.38%)	10 (3.77%)	0.015
Any type of hospital readmission	62 (11.7%)	33 (12.5%)	29 (10.9%)	0.674
3-year mortality	47 (8.88%)	24 (9.09%)	23 (8.68%)	0.989
Overall Survival (3-year)	90.6 (95%CI 88.1; 93.2)	90.4 (95%CI 86.8; 94.1)	90.9 (95%CI 87.4; 94.5)	0.819

Total, n=184	GI endoscopy performed	GI endoscopy deferred and/or cancelled
N, %	154 (84)	30 (16)
Sex, male (%)	89 (58)	16 (53)
Age (years), mean (±SD)	72 (12.8)	71 (14)
Type of exam Endoscopy, n (%) Colonoscopy, n (%) Endoscopy + Colonoscopy, n (%) Flexible sigmoidoscopy, n (%)	68 (44) 28 (18) 55 (36) 3 (19)	13 (42) 6 (19) 10 (33) 1 (33)
Indication, n Anemia Diarrhea Dysphagia Epigastric pain Chronic liver disease Suspected GI neoplasia^¥ Suspected upper GI neoplasia Suspected colorectal neoplasia Suspected GI bleeding	42 5 8 3 7 44 14 15 4	5 - - 1 - 20 - - 4
Relevant endoscopy findings, n Hypopharyngeal neoplasm Grade C, D esophagitis Esophageal neoplasia Esophagogastric varices Gastric angiodysplasia Gastric neoplasia Neoplastic infiltration of duodenum Colorectal neoplasia Inconclusive (poor bowel preparation)	2 2 2 6 3 11 2 7 3	-
Motive to defer and/or cancel, n Awaiting imaging results Clinical deterioration Respiratory distress End-of-life care Evidence of myeloma Evidence of ovarian cancer Recent endoscopic evaluation Without analytical or clinical evidence of bleeding Death	-	8 5 5 2 1 2 2 4 1
Death during hospitalization, n (%)	17 (11)	10 (33)
Death within 30 days after discharge, n (%)	2 (1.8)	3 (15)

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