Activation of the Sonic hedgehog signaling pathway affects multiple aspects of mitochondria in hippocampal neurons. It increases mitochondrial mass significantly, reduces fission, and promotes elongation. It also protects neurons against stress.

Background: Selenoprotein H (SelH), a proposed redox-responsive DNA-binding protein, is little-studied. Results: SelH shRNA cells display severe proliferation defects and accelerated senescence with abnormal responses to DNA damage and oxidative stress. Conclusion: SelH suppresses senescence and may have important roles in gatekeeping genomic integrity. Significance: Learning how SelH keeps senescence in check is crucial for advancing our understanding linking selenium and aging intervention.

The hierarchies of tissue selenium distribution and selenotranscriptomes are thought to critically affect healthspan and longevity. We determined selenium status and selenotranscriptomes in response to long-term dietary selenium deficiency and age in tissues of male and female mice. Weanling telomerase RNA component knockout C57BL/6 mice were fed a selenium-deficient (0.03 mg Se/kg) Torula yeast-based AIN-93G diet or a diet supplemented with sodium selenate (0.15 mg Se/kg) until age 18 or 24 mo. Plasma, hearts, kidneys, livers, and testes were collected to assay for selenotranscriptomes, selected selenoproteins, and tissue selenium concentrations. Data were analyzed with the use of 2-factor ANOVA (diet × age) in both sexes. Dietary selenium deficiency decreased ( ≤ 0.05) selenium concentrations (65-72%) and glutathione peroxidase (GPX) 3 (82-94%) and selenoprotein P (SELENOP) (17-41%) levels in the plasma of both sexes of mice and mRNA levels (9-68%) of 4, 4, and 12 selenoproteins in the heart, kidney, and liver of males, respectively, and 5, 16, and 14 selenoproteins, respectively, in females. Age increased selenium concentrations and SELENOP levels (27% and 30%, respectively; ≤ 0.05) in the plasma of males only but decreased (12-46%; < 0.05) mRNA levels of 1, 5, and 13 selenoproteins in the heart, kidney, and liver of males, respectively, and 6, 5, and 0 selenoproteins, respectively, in females. Among these mRNAs, selenoprotein H (), selenoprotein M (), selenoprotein W (), methionine--sulfoxide reductase 1 (), ,, thioredoxin reductase 1 (), , selenoprotein S (), selenoprotein F (), and selenoprotein O () responded in parallel to dietary selenium deficiency and age in ≥1 tissue or sex, or both. Dietary selenium deficiency upregulated (40-160%; ≤ 0.05) iodothyronine deiodinase 2 () and selenoprotein N () in the kidneys of males. Age upregulated (11-44%; < 0.05) in the kidneys of males, selenoprotein K () and selenoprotein I () in the kidneys of females, and and in the testes. These results illustrate tissue-specific sexual dimorphisms of selenium status and selenotranscriptomes because of dietary selenium deficiency and age.

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