Evidence map›Paper›PMID 40617521›Full record

ArticleExperimental gerontology2025

Exploring age-related iron dysregulation: effects on longevity, body size, and behavior in C. elegans.

Rola S Zeidan, Pearl Ebea-Ugwuanyi, Shannon Sykes, Natalia Evripidou, Evelyn Pan, Zachary Markovich, Yi Sheng, Sung Min Han, Christiaan Leeuwenburgh, Rui Xiao

Abstract read
In one paragraph

Article in Experimental gerontology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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.

Rola S ZeidanDepartment of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, FL, USA; Institute on Aging, University of Florida, Gainesville, FL 32610, USA.
Pearl Ebea-UgwuanyiDepartment of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Shannon SykesDepartment of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Natalia EvripidouDepartment of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Evelyn PanDepartment of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Zachary MarkovichDepartment of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Florida Chemical Senses Institute, University of Florida, Gainesville, FL 32610, USA.
Yi ShengDepartment of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Sung Min HanDepartment of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Christiaan LeeuwenburghDepartment of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Institute on Aging, University of Florida, Gainesville, FL 32610, USA. Electronic address: cleeuwen@ufl.edu.
Rui XiaoDepartment of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Institute on Aging, University of Florida, Gainesville, FL 32610, USA; Florida Chemical Senses Institute, University of Florida, Gainesville, FL 32610, USA; Genetics Institute, University of Florida, Gainesville, FL 32610, USA; UF Health Cancer Center, University of Florida, Gainesville, FL 32610, USA. Electronic address: rxiao@ufl.edu.

Funding

Dissecting the mechanisms of Alzheimer's disease (AD)-related smell loss in a C. elegans AD modelR01AG063766 · NIA · UNIVERSITY OF FLORIDA · PI XIAO, RUI · 2019 to 2023
$1.9M
NIA NIH HHS R01 AG063766
6 · The paper itself

Abstract

Age-related iron accumulation is widely observed in various species and significantly impacts physiological processes. However, systematic investigation into how age-related iron dysregulation affects different life traits is still limited. This study utilizes the model organism C. elegans to examine the roles of iron regulatory genes throughout different life stages, focusing on their effects on iron homeostasis, longevity, mobility, size, and mechanosensation. Our expression analysis indicated that most iron-related genes are generally upregulated by day 15, with some peaking earlier, suggesting their crucial role in mid-life iron regulation. Lifespan assays revealed that certain mutants of non-transferrin bound iron (NTBI) uptake regulators, such as smf-1 and smf-3, are linked to extended lifespans, while zipt-17 mutants showed slightly reduced longevity. Mobility assessments indicated significant declines in speed among several mutant strains by day 7, pointing to mobility issues related to altered iron metabolism. Body size measurements varied considerably among mutant strains, with some demonstrating significant changes over time. Behavioral analyses found that most strains exhibited mechanosensory responses similar to wild-type worms at day 1; however, certain mutants displayed different rates of response reduction by day 7. FerroOrange staining confirmed increased iron accumulation with age in most mutant strains, except for zipt-16 and zipt-17, highlighting the connection between iron regulation and aging. Collectively, our current findings demonstrate that iron regulatory genes in C. elegans play diverse and critical roles in maintaining iron homeostasis, influencing lifespan, mobility, body size, and behavioral responses throughout the organism's life. These findings deepen our understanding of iron regulation's impact on health and aging in C. elegans.

Indexed as

AgingBehavior, AnimalBody SizeCaenorhabditis elegansIronLongevityAnimalsCaenorhabditis elegans ProteinsHomeostasisMutationCaenorhabditis elegans ProteinsIronAgingBehaviorC. elegansIronMechanosensationMobility

Identifiers

PMID40617521
PMCPMC13162325

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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.