%0 Journal Article
%T Anti©\aging drugs reduce hypothalamic inflammation in a sex©\specific manner
%A Gillian Cady
%A Richard A. Miller
%J Archive of "Aging Cell".
%D 2017
%R 10.1111/acel.12590
%X Aging leads to hypothalamic inflammation, but does so more slowly in mice whose lifespan has been extended by mutations that affect GH/IGF©\1 signals. Early©\life exposure to GH by injection, or to nutrient restriction in the first 3 weeks of life, also modulate both lifespan and the pace of hypothalamic inflammation. Three drugs extend lifespan of UM©\HET3 mice in a sex©\specific way: acarbose (ACA), 17©\¦Á©\estradiol (17¦ÁE2), and nordihydroguaiaretic acid (NDGA), with more dramatic longevity increases in males in each case. In this study, we examined the effect of these anti©\aging drugs on neuro©\inflammation in hypothalamus and hippocampus. We found that age©\associated hypothalamic inflammation is reduced in males but not in females at 12 months of age by ACA and 17¦ÁE2 and at 22 months of age in NDGA©\treated mice. The three drugs blocked indices of hypothalamic reactive gliosis associated with aging, such as Iba©\1©\positive microglia and GFAP©\positive astrocytes, as well as age©\associated overproduction of TNF©\¦Á. This effect was not observed in drug©\treated female mice or in the hippocampus of the drug©\treated animals. On the other hand, caloric restriction (CR; an intervention that extends the lifespan in both sexes) significantly reduced hypothalamic microglia and TNF©\¦Á in both sexes at 12 months of age. Together, these results suggest that the extent of drug©\induced changes in hypothalamic inflammatory processes is sexually dimorphic in a pattern that parallels the effects of these agents on mouse longevity and that mimics the changes seen, in both sexes, of long©\lived nutrient restricted or mutant mice
%K Acarbose
%K aging
%K hypothalamus
%K inflammation
%K NDGA
%K longevity
%K sexual dimorphism
%K 17©\¦Á Estradiol
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506421/