title: Opposing impacts on healthspan and longevity by limiting dietary selenium in telomere dysfunctional mice.
abstract: 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 microRNA 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.
authors.affiliation: Department of Nutrition and Food Science, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Wu
authors.affiliation: Department of Food Science, Nutrition and Health Promotion, Mississippi State University, Mississippi State, MS, 39762, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Nutrition and Food Science, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Elliot
authors.initials: E
authors.lastname: Mattson
authors.affiliation: Department of Molecular & Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, 21205, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Witwer
authors.affiliation: USDA, Agricultural Research Service, Grand Forks Human Nutrition Center, Grand Forks, ND, 58202, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Cao
authors.affiliation: USDA, Agricultural Research Service, Grand Forks Human Nutrition Center, Grand Forks, ND, 58202, USA.
authors.forename: Huawei
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Department of Epidemiology and Biostatistics, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.affiliation: USDA, Agricultural Research Service, Grand Forks Human Nutrition Center, Grand Forks, ND, 58202, USA.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Combs
authors.affiliation: Department of Nutrition and Food Science, University of Maryland, College Park, MD, 20742, USA.|Department of Food Science, Nutrition and Health Promotion, Mississippi State University, Mississippi State, MS, 39762, USA.
authors.forename: Wen-Hsing
authors.initials: WH
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D015536:Down-Regulation / Q000187:drug effects; D020869:Gene Expression Profiling; D042822:Genomic Instability / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006262:Health; D006657:Histones / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008136:Longevity / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012643:Selenium / Q000097:blood / Q000494:pharmacology*; D016019:Survival Analysis; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000187:drug effects / Q000378:metabolism*
chemical_list: D006657:Histones; D007328:Insulin; D035683:MicroRNAs; D012333:RNA, Messenger; C475961:gamma-H2AX protein, mouse; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase; D012643:Selenium; D005947:Glucose
keywords: accelerated aging; antioxidant; longevity regulation; mouse models; selenium; trade-offs