PubAg

Main content area

Opposing impacts on healthspan and longevity by limiting dietary selenium in Telomere Dysfunctional mice

Author:
Wu, Ryan T., Cao, Lei, Mattson, Elliot, Witwer, Kenneth W., Cao, Jay, Zeng, Huawei, He, Xin, Combs., Gerald F. Jr, Cheng, Wen-Hsing
Source:
Aging Cell 2017 v.16 no.1 pp. 125-135
ISSN:
1474-9718
Subject:
DNA damage, alopecia, cataract, cell senescence, diet, gene expression, glucose tolerance, insulin, insulin resistance, knockout mutants, longevity, messenger RNA, mice, microRNA, models, nutrient deficiencies, osteoporosis, pancreas, selenium, sodium selenate, telomerase, telomeres, tissue repair, weanlings
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.
Agid:
5832844
Handle:
10113/5832844