Opposing impacts on healthspan and longevity by limiting dietary selenium in telomere dysfunctional mice
Open accessAbstract
Summary: Selenium (Se) is a trace metalloid essential for life, but its nutritional and physiological roles during the aging process remain elusive. While telomere attrition contributes to replicative senescence mainly through persistent DNA damage response, such an aging process is mitigated in mice with inherently long telomeres. Here, weanling third generation telomerase RNA component knockout mice carrying short telomeres were fed a Se‐deficient basal diet or the diet supplemented with 0.15 ppm Se as sodium selenate to be nutritionally sufficient throughout their life. Dietary Se deprivation delayed wound healing and accelerated incidence of osteoporosis, gray hair, alopecia, and cataract, but surprisingly promoted longevity. Plasma micro RNA profiling revealed a circulating signature of Se deprivation, and subsequent ontological analyses predicted dominant changes in metabolism. Consistent with this observation, dietary Se deprivation accelerated age‐dependent declines in glucose tolerance, insulin sensitivity, and glucose‐stimulated insulin production in the mice. Moreover, DNA damage and senescence responses were enhanced and Pdx1 and MafA mRNA expression were reduced in pancreas of the Se‐deficient mice. Altogether, these results suggest a novel model of aging with conceptual advances, whereby Se at low levels may be considered a hormetic chemical and decouple healthspan and longevity.
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The structural and functional roles of zinc, selenium, magnesium, copper, and manganese are crucial for antioxidant defence.
“Concerning the latter, the structural and functional roles of a few minerals such as zinc (Zn), selenium (Se), magnesium (Mg) copper (Cu) and manganese (Mn) is crucial (Table 5) [409,410,411,412,413,414,415,416,417,418,419,420].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [415]
Selenium deprivation in mice accelerates DNA damage, senescence, and aging-related processes.
“Furthermore, Se deprivation in mice has been found to accelerate DNA damage, senescence, and aging-related processes [415].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [415]
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- Authors
- Wu, R. T., Cao, L., Mattson, E., Witwer, K. W., Cao, J., Zeng, H., He, X., Combs, G. F., & Cheng, W.
- Affiliations
- University of Maryland, College Park (US)
- Mississippi State University (US)
- Johns Hopkins University (US)
- Agricultural Research Service (US)
- Corresponding author
- Cheng, Wen‐Hsing
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2016-09-21
- Volume
- 16
- Issue
- 1
- Pages
- 125-135
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC5242309
- OpenAlex
- W2522797895
- Cited by
- 37
- References
- 45
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 3
- FWCI
- 4.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Agriculture
- Agricultural Research Service (5450‐51000‐050‐00D, 3062‐51000‐053‐00D)
- Johns Hopkins University
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- dietary selenium, selenium deficiency, telomere dysfunction, aging, longevity, healthspan, replicative senescence, DNA damage response, wound healing, osteoporosis, gray hair, cataract, miRNA expression profiling, glucose tolerance, insulin sensitivity, pancreatic beta cells, PDX1, MafA, hormesis
- MeSH terms
- Animals, Body Weight, Diet, Glucose, Health, Histones, Insulin, Longevity, Male, Mice, Inbred C57BL, Pancreas, Phenotype, RNA, RNA, Messenger, Selenium, Down-Regulation, Survival Analysis, Telomere, Telomerase, Gene Expression Profiling, MicroRNAs, Genomic Instability, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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