Dietary Selenium Deprivation Oppositely Impacts Longevity and Healthspan in Telomere Dysfunctional Mice

The study investigated the effects of dietary selenium (Se) deprivation on telomere dysfunctional mice with humanized short telomeres. Mice fed a Se-deficient diet exhibited delayed wound healing and accelerated age-related degeneration, including osteoporosis, grey hair, alopecia, cataracts, and hyperglycemia. Despite these negative health impacts, Se deprivation paradoxically promoted longevity. Plasma microRNA profiling indicated significant changes in metabolism due to Se deprivation. Additionally, Se deprivation accelerated declines in glucose tolerance, insulin production, and sensitivity, and increased DNA damage and senescence in the pancreas. Selenotranscriptomic and metagenomic analyses highlighted key selenoproteins and gut bacteria involved in the response to Se deprivation. The findings suggested that low Se levels might act as a hormetic chemical, decoupling healthspan and longevity.