Evidence map›Paper›PMID 34915110›Full record

ArticleExperimental gerontology2022

Advanced age exacerbates intestinal epithelial permeability after burn injury in mice.

Kevin M Najarro, Devin M Boe, Travis M Walrath, Juliet E Mullen, Madison T Paul, John H Frankel, Holly J Hulsebus, Juan-Pablo Idrovo, Rachel H McMahan, Elizabeth J Kovacs

Open access · greenAbstract read
In one paragraph

Article in Experimental gerontology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.0field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Article
  3. Impaired intestinal cell proliferation parallels increased senescence after burn injury in aged mice.American journal of physiology. Gastrointestinal and liver physiology · 2026
    Article
  4. Review
  5. Post-burn Lung Inflammation Is Associated With Induction of Pulmonary Cathelicidin-related Antimicrobial Peptide and S100a8 in Mice.Journal of burn care & research : official publication of the American Burn Association · 2025
    Article
  6. Article
  7. Reducing the excessive inflammation after burn injury in aged mice by maintaining a healthier intestinal microbiome.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  8. Article
  9. Evaluation ofMicroorganisms · 2023
    Article
  10. Article
  11. Article
  12. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Kevin M NajarroDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America.
Devin M BoeDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America; Immunology Graduate Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America; Medical Scientist Training Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, United States of America.
Travis M WalrathDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America.
Juliet E MullenDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America.
Madison T PaulDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America.
John H FrankelDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America.
Holly J HulsebusDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America; Immunology Graduate Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America.
Juan-Pablo IdrovoDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America.
Rachel H McMahanDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America; GI and Liver Innate Immune Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America.
Elizabeth J KovacsDepartment of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America; Immunology Graduate Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America; Medical Scientist Training Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, United States of America; GI and Liver Innate Immune Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, United States of America. Electronic address: Elizabeth.Kovacs@CUAnschutz.edu.
University of Colorado Denver · USUniversity of Colorado Anschutz Medical Campus · US

Funding

University of Colorado Aging Training GrantT32AG000279 · NIA · UNIVERSITY OF COLORADO DENVER · PI Kerrie Moreau · 2001 to 2026
$10.1M
Aging, macrophage mediators, and burn trauma: SupplementR01AG018859 · NIA · UNIVERSITY OF COLORADO DENVER · PI KOVACS, ELIZABETH J. · 2001 to 2024
$7.6M
Alcohol and Burn Trauma: Multi-organ Inflammatory ResponsesR35GM131831 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI ELIZABETH J. KOVACS · 2019 to 2026
$3.5M
Hepatic Response in Advance Age after Burn InjuryK08GM134185 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI IDROVO, JUAN PABLO · 2019 to 2023
$945k
Ethanol effects on pulmonary innate immunity in a murine model of agingF31AA027687 · NIAAA · UNIVERSITY OF COLORADO DENVER · PI HULSEBUS, HOLLY J · 2019 to 2021
$101k
Multi-organ Inflammatory Responses after Burn TraumaI01BX004335 · VA · VA EASTERN COLORADO HEALTH CARE SYSTEM · PI KOVACS, ELIZABETH J. · 2019 to 2023
–
BLRD VA I01 BX004335NIAAA NIH HHS F31 AA027687NIA NIH HHS R01 AG018859NIA NIH HHS T32 AG000279NIGMS NIH HHS K08 GM134185NIGMS NIH HHS R35 GM131831
6 · The paper itself

Abstract

backgroundAdvanced age is an independent risk factor for morbidity and mortality after burn injury. Following burn, the intestines can become permeable leading to the leakage of bacteria and their products from the lumen of the ileum to the portal and systemic circulation. Here, we sought to determine the effects of advanced age on intestinal permeability post burn injury and assess intestinal inflammatory biomarkers.

methodsYoung (4-5 months) and aged (18-22 months) female BALB/cBy mice were subjected to a 12-15% total body surface area (TBSA) sham or burn injury. 24 h after injury, mice were euthanized, and organs collected. Colony-forming units (CFU) were counted from plated mesenteric lymph nodes (MLN). Gene expression of ileal tight junctional proteins, occludin and zonula occludens 1 (ZO-1), in addition to ileal damage associated molecular pattern (DAMP) proteins, S100A8 and S100A9, as well as ileal inflammatory markers IL-6 and TNF-α were measured by qPCR. Intestinal cell death was measured by ELISA. Intestinal permeability was determined by FITC fluorescence in serum; 4kD FITC-dextran was given by oral gavage 3 h before euthanasia.

resultsAged mice subjected to burn injury had increased intestinal permeability as evidenced by a 5.8-fold higher level of FITC-dextran in their serum when compared to all other groups (p < 0.05). In addition, aged burn-injured mice exhibited heightened bacterial accumulation in the MLN with a 15.5-fold increase over all other groups (p < 0.05). Histology of ileum failed to show differences in villus length among all groups. Analysis of ileal tight junctional proteins and inflammatory marker gene expression revealed no difference in Ocln, Tjp1, Il6, or Tnf expression among all groups, but 2.3 and 2.9-fold upregulation of S100a8 and S100a9, respectively, in aged burn-injured mice relative to both young groups and aged sham-injured mice (p < 0.05). Lastly, cell death in the ileum was elevated more than two-fold in aged burn-injured mice relative to young animals regardless of injury (p < 0.05).

conclusionsThese data demonstrate that advanced age exacerbates intestinal epithelial permeability after burn injury. Heightened apoptosis may be responsible for the elevated intestinal leakiness and accumulation of bacteria in mesenteric lymph nodes. In addition, S100a8/9 may serve as a biomarker of elevated inflammation within the intestine.

Indexed as

IntestinesTight JunctionsAnimalsFemaleIntestinal MucosaMiceOccludinPermeabilityOccludinAgingBiomarkerBurnDAMPsIntestinal permeabilityTight junction

Identifiers

PMID34915110
PMCPMC9188353
OpenAlexW4200539812

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.