Dietary selenium deficiency accelerates the onset of aging-related gut microbial changes in aged telomere-humanized mice, with Akkermansia muciniphila being the most prominent and alleviating selenium deficiency-induced Type 2 Diabetes
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- dc.contributor.author Huang, Ying-Chen
- dc.contributor.author Lu, Hsin-Yi
- dc.contributor.author Zhang, Li
- dc.contributor.author Olivier, Alicia
- dc.contributor.author Wu, Tung-Lung
- dc.contributor.author Hsu, Chuan-Yu
- dc.contributor.author LeGrand, Caleb
- dc.contributor.author Zeng, Huawei
- dc.contributor.author Curran, Samantha
- dc.contributor.author Wing, Qingzhou
- dc.contributor.author Nannapaneni, Ramakrishna
- dc.contributor.author Zhang, Xue
- dc.contributor.author Ticó, Max
- dc.contributor.author Mariotti, Marco, 1984-
- dc.contributor.author Wu, Ryan T. Y.
- dc.contributor.author Combs, Gerald F.
- dc.contributor.author Cheng, Wen-Hsing
- dc.date.accessioned 2025-09-08T11:48:48Z
- dc.date.available 2025-09-08T11:48:48Z
- dc.date.issued 2025
- dc.description.abstract Previous studies have shown that dietary selenium (Se) deficiency in mice reshapes gut microbiota, exacerbates healthspan deterioration (e.g., type 2 diabetes), and paradoxically activates beneficial longevity pathways. This study demonstrated that dietary Se deficiency accelerated many age-related gut microbial changes in aged telomere-humanized C57BL/6J diabetic mice in a sexually dimorphic manner, with Akkermansia muciniphila showing the greatest enrichment in males. However, dietary Se deficiency did not enrich A. muciniphila in mature or middle-aged male C57BL/6J wild-type mice. Oral gavage of A. muciniphila alleviated Se deficiency-induced type 2 diabetes-like symptoms, reversed mucosal barrier dysfunction and gut inflammation, and resulted in a trend of symbiotic and competitive suppression changes in certain gut bacteria in mature wild-type mice under conventional conditions. The beneficial effects of A. muciniphila appeared to be independent of selenoproteins sensitive to dietary Se deficiency, such as GPX1, SELENOH, and SELENOW, in the liver and muscle. Altogether, these results show that dietary Se deficiency accelerates age-related A. muciniphila enrichment specifically in aged male mice with severe insulin resistance and pancreatic senescence, indicating a potential hormetic response to Se deficiency through reshaped gut microbiota, which alleviates hyperglycemia and partially compensates for healthspan decline.
- dc.format.mimetype application/pdf
- dc.identifier.citation Huang YC, Lu HY, Zhang L, Olivier A, Wu TL, Hsu CY, et al. Dietary selenium deficiency accelerates the onset of aging-related gut microbial changes in aged telomere-humanized mice, with Akkermansia muciniphila being the most prominent and alleviating selenium deficiency-induced Type 2 Diabetes. Aging Cell. 2025 Aug;24(8):e70130. DOI: 10.1111/acel.70130
- dc.identifier.doi http://dx.doi.org/10.1111/acel.70130
- dc.identifier.issn 1474-9718
- dc.identifier.uri http://hdl.handle.net/10230/71150
- dc.language.iso eng
- dc.publisher Wiley
- dc.relation.ispartof Aging Cell. 2025 Aug;24(8):e70130
- dc.rights © 2025 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.other Seleni
- dc.title Dietary selenium deficiency accelerates the onset of aging-related gut microbial changes in aged telomere-humanized mice, with Akkermansia muciniphila being the most prominent and alleviating selenium deficiency-induced Type 2 Diabetes
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion