Cargando…

Opposing impacts on healthspan and longevity by limiting dietary selenium in telomere dysfunctional mice

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 in...

Descripción completa

Detalles Bibliográficos
Autores principales: Wu, Ryan T., Cao, Lei, Mattson, Elliot, Witwer, Kenneth W., Cao, Jay, Zeng, Huawei, He, Xin, Combs, Gerald F., Cheng, Wen‐Hsing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242309/
https://www.ncbi.nlm.nih.gov/pubmed/27653523
http://dx.doi.org/10.1111/acel.12529
_version_ 1782496320215318528
author Wu, Ryan T.
Cao, Lei
Mattson, Elliot
Witwer, Kenneth W.
Cao, Jay
Zeng, Huawei
He, Xin
Combs, Gerald F.
Cheng, Wen‐Hsing
author_facet Wu, Ryan T.
Cao, Lei
Mattson, Elliot
Witwer, Kenneth W.
Cao, Jay
Zeng, Huawei
He, Xin
Combs, Gerald F.
Cheng, Wen‐Hsing
author_sort Wu, Ryan T.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5242309
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-52423092017-02-01 Opposing impacts on healthspan and longevity by limiting dietary selenium in telomere dysfunctional mice Wu, Ryan T. Cao, Lei Mattson, Elliot Witwer, Kenneth W. Cao, Jay Zeng, Huawei He, Xin Combs, Gerald F. Cheng, Wen‐Hsing Aging Cell Original Articles 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. John Wiley and Sons Inc. 2016-09-21 2017-02 /pmc/articles/PMC5242309/ /pubmed/27653523 http://dx.doi.org/10.1111/acel.12529 Text en © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Wu, Ryan T.
Cao, Lei
Mattson, Elliot
Witwer, Kenneth W.
Cao, Jay
Zeng, Huawei
He, Xin
Combs, Gerald F.
Cheng, Wen‐Hsing
Opposing impacts on healthspan and longevity by limiting dietary selenium in telomere dysfunctional mice
title Opposing impacts on healthspan and longevity by limiting dietary selenium in telomere dysfunctional mice
title_full Opposing impacts on healthspan and longevity by limiting dietary selenium in telomere dysfunctional mice
title_fullStr Opposing impacts on healthspan and longevity by limiting dietary selenium in telomere dysfunctional mice
title_full_unstemmed Opposing impacts on healthspan and longevity by limiting dietary selenium in telomere dysfunctional mice
title_short Opposing impacts on healthspan and longevity by limiting dietary selenium in telomere dysfunctional mice
title_sort opposing impacts on healthspan and longevity by limiting dietary selenium in telomere dysfunctional mice
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242309/
https://www.ncbi.nlm.nih.gov/pubmed/27653523
http://dx.doi.org/10.1111/acel.12529
work_keys_str_mv AT wuryant opposingimpactsonhealthspanandlongevitybylimitingdietaryseleniumintelomeredysfunctionalmice
AT caolei opposingimpactsonhealthspanandlongevitybylimitingdietaryseleniumintelomeredysfunctionalmice
AT mattsonelliot opposingimpactsonhealthspanandlongevitybylimitingdietaryseleniumintelomeredysfunctionalmice
AT witwerkennethw opposingimpactsonhealthspanandlongevitybylimitingdietaryseleniumintelomeredysfunctionalmice
AT caojay opposingimpactsonhealthspanandlongevitybylimitingdietaryseleniumintelomeredysfunctionalmice
AT zenghuawei opposingimpactsonhealthspanandlongevitybylimitingdietaryseleniumintelomeredysfunctionalmice
AT hexin opposingimpactsonhealthspanandlongevitybylimitingdietaryseleniumintelomeredysfunctionalmice
AT combsgeraldf opposingimpactsonhealthspanandlongevitybylimitingdietaryseleniumintelomeredysfunctionalmice
AT chengwenhsing opposingimpactsonhealthspanandlongevitybylimitingdietaryseleniumintelomeredysfunctionalmice