2014
DOI: 10.1111/acel.12194
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Abstract: Rapamycin, an inhibitor of mTOR kinase, increased median lifespan of genetically heterogeneous mice by 23% (males) to 26% (females) when tested at a dose threefold higher than that used in our previous studies; maximal longevity was also increased in both sexes. Rapamycin increased lifespan more in females than in males at each dose evaluated, perhaps reflecting sexual dimorphism in blood levels of this drug. Some of the endocrine and metabolic changes seen in diet-restricted mice are not seen in mice exposed … Show more

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Cited by 479 publications
(516 citation statements)
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“…Although the current (C2011) cohort did not contain any mice given Rapa alone, we thought it would be of interest to compare the survival of mice receiving both Rapa and Met to survival of mice treated with the same Rapa dose in previous years, C2006 and C2009 (Miller et al ., 2011, 2014). Results are shown in Table S4 (Supporting information).…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…Although the current (C2011) cohort did not contain any mice given Rapa alone, we thought it would be of interest to compare the survival of mice receiving both Rapa and Met to survival of mice treated with the same Rapa dose in previous years, C2006 and C2009 (Miller et al ., 2011, 2014). Results are shown in Table S4 (Supporting information).…”
Section: Resultsmentioning
confidence: 99%
“…Significant effects on longevity, in one or both sexes, have been published for 6 of the tested agents: aspirin (Strong et al ., 2008), nordihydroguaiaretic acid (NDGA) (Strong et al ., 2008; Harrison et al ., 2014), rapamycin (Harrison et al ., 2009; Miller et al ., 2011, 2014), acarbose (ACA) (Harrison et al ., 2014), methylene blue (Harrison et al ., 2014), and 17‐α‐estradiol (17aE2) (Harrison et al ., 2014). Here, we report survival analyses for mice treated with additional test agents, including ursodeoxycholic acid (UDCA), Protandim (Prot) and fish oil (FO), metformin (Met), or with the combination of Met plus rapamycin (Rapa).…”
Section: Introductionmentioning
confidence: 99%
“…The degree of hepatic protein RR reduction was smallest in response to 14 ppm Rapa treatment, which is established to extend maxLS by 12%, and greatest in Snell Dwarf mice, which live 40% longer than their Het/WT counterparts, while hepatic protein RRs were reduced to an intermediate level in response to 40% CR, which extends maxLS by 18% (Fig. 4) (Blackwell et al ., 1995; Flurkey et al ., 2002; Harrison et al ., 2009; Miller et al ., 2011, 2013). These data suggest that a reduction in hepatic protein RRs may be an early BM not only qualitatively of maxLS extension but also quantitatively of the degree of maxLS extension in mice.…”
Section: Resultsmentioning
confidence: 99%
“…A recent ITP study found that Rapa treatment extends maxLS in mice in a dose‐dependent manner at doses of 4.7 and 14 ppm but that there is no additional extension of maxLS at 42 ppm relative to 14 ppm (Fig. 5A; Miller et al ., 2013). The question that we specifically addressed here was whether changes in hepatic protein RRs were predictive of the degree of maxLS extension at these different doses of Rapa and would therefore plateau at 14 ppm.…”
Section: Resultsmentioning
confidence: 99%
“…6A). We also observed sex‐based differences in the trajectory of mTOR signaling with age, which may help to explain the sexually dimorphic impact of rapamycin on lifespan (Miller et al ., 2014). In the fasted state, sex‐based differences in S6 phosphorylation in the heart are observed (Fig.…”
Section: Discussionmentioning
confidence: 99%