Silencing of the Metabolic Gene HKDC1 Is Associated With Aging and Neurodegeneration in Mice and Humans.
Overview
- Division of Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago, Chicago, Illinois, USA
- Division of Nephrology, University of Illinois at Chicago, Chicago, Illinois, USA
- Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA
- Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA
- Department of Anatomy and Cell Biology, University of Illinois Chicago, Chicago, Illinois, USA
- Jesse Brown Veterans Affair Medical Center, Chicago, Illinois, USA
Abstract
Increased life expectancy brought about by improved healthcare and lifestyle has heightened the challenge of neurodegenerative disorders like Alzheimer's disease (AD) and other age‐related disorders. Neurodegeneration is known to be accompanied by loss of memory, changes in brain morphology, and neuroinflammation, and multiple factors contribute to the progression and pathogenesis of the condition. Of these factors, metabolic dysregulation is known to influence the process, but the precise mechanisms remain unexplored. In this study, we investigated the brain‐specific role of the metabolic enzyme hexokinase domain‐containing 1 (HKDC1) in neurodegeneration and observed that HKDC1 expression declines in humans with cognitive decline, which matches similar findings in mouse models of AD and aging. We observed age‐dependent anxiety, compromised memory and learning, senescence, neuroinflammation, and mitochondrial function deficit in HKDC1‐brain knockout mouse models. Furthermore, Chromatin immunoprecipitation (ChIP), RT‐PCR, and Western blotting assays reveal that an age‐related decline in HKDC1 expression stems from changes in chromatin conformation, which decrease the ability of transcription factor EB to regulate its transcription. These findings suggest an important role for the metabolic gene HKDC1 in the brain in relation to cognitive decline and the progression of neurodegeneration in mice and humans.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- figshare:29497418, at figshare; found in “Data Availability Statement”
Data Availability Statement
All data generated from this study has been deposited in the Figshare repository at https://
Reproduced under the paper's license (CC BY), from the paper cited above.
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 6 keywords, 9 MeSH terms, 4 funders, 64 references.
Cite
This paper
Farooq, Z., Ilievski, V., Boyett, J., Jorgensen, J., Pan, Y., Kelly, T., Bennett, D., Lazarov, O., & Layden, B. T. (2026). Silencing of the Metabolic Gene HKDC1 Is Associated With Aging and Neurodegeneration in Mice and Humans. Aging cell, 25(3), e70419. https://
BibTeX
@article{farooq2026silen
author = {Farooq, Zeenat and Ilievski, Vladimir and Boyett, James and Jorgensen, Julianne and Pan, Yang and Kelly, Tanika and Bennett, David and Lazarov, Orly and Layden, Brian T},
title = {{Silencing of the Metabolic Gene HKDC1 Is Associated With Aging and Neurodegeneration in Mice and Humans}},
journal = {Aging cell},
year = {2026},
month = mar,
volume = {25},
number = {3},
pages = {e70419},
publisher = {Wiley},
issn = {1474-9718},
doi = {10.1111/
url = {https://
pmid = {41736382},
pmcid = {PMC12932916}
}
RIS
TY - JOUR
AU - Farooq, Zeenat
AU - Ilievski, Vladimir
AU - Boyett, James
AU - Jorgensen, Julianne
AU - Pan, Yang
AU - Kelly, Tanika
AU - Bennett, David
AU - Lazarov, Orly
AU - Layden, Brian T
TI - Silencing of the Metabolic Gene HKDC1 Is Associated With Aging and Neurodegeneration in Mice and Humans
T2 - Aging cell
J2 - Aging Cell
PY - 2026
DA - 2026/
VL - 25
IS - 3
SP - e70419
SN - 1474-9718
PB - Wiley
DO - 10.1111/
UR - https://
LA - en
ER -
CSL-JSON
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