2014
DOI: 10.18632/aging.100688
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Abstract: The inhibition of mTOR (mechanistic target of rapamycin) by the macrolide rapamycin has many beneficial effects in mice, including extension of lifespan and reduction or prevention of several age-related diseases. At the same time, chronic rapamycin treatment causes impairments in glucose metabolism including hyperglycemia, glucose intolerance and insulin resistance. It is unknown whether these metabolic effects of rapamycin are permanent or whether they can be alleviated. Here, we confirmed that rapamycin cau… Show more

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Cited by 61 publications
(63 citation statements)
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References 45 publications
(87 reference statements)
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“…We treated 9‐week‐old male C57BL/6J mice for 2 weeks with vehicle or 2 mg/kg rapamycin every day (1×/day) or weekly (1×/7 days), and analyzed the effect on glucose tolerance. We performed a fasting glucose tolerance test 7 days after the most recent rapamycin treatment of the weekly (1×/7 days) group; the effects of chronic rapamycin treatment on glucose tolerance persist for 2 weeks (Yang et al ., 2012; Liu et al ., 2014). …”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…We treated 9‐week‐old male C57BL/6J mice for 2 weeks with vehicle or 2 mg/kg rapamycin every day (1×/day) or weekly (1×/7 days), and analyzed the effect on glucose tolerance. We performed a fasting glucose tolerance test 7 days after the most recent rapamycin treatment of the weekly (1×/7 days) group; the effects of chronic rapamycin treatment on glucose tolerance persist for 2 weeks (Yang et al ., 2012; Liu et al ., 2014). …”
Section: Resultsmentioning
confidence: 99%
“…The effect of chronic rapamycin treatment on AKT S473 phosphorylation can be difficult to observe and is time sensitive (Schreiber et al ., 2015), and so we may have only observed this effect in skeletal muscle due to the time point utilized. The impact of chronic rapamycin on AKT S473 phosphorylation is also influenced by diet (Liu et al ., 2014). The current study utilized a different chow (LabDiet 5001) than we utilized in our previous studies (ProLab RMH 3000), yet the phenotypes of rapamycin‐treated mice were identical.…”
Section: Discussionmentioning
confidence: 99%
“…(164) The mechanisms of the effect of rapamycin are pleiotropic, including inhibition of protein synthesis, alteration of transcriptomes, modulation of inflammation, and improvement of cerebral blood flow, in addition to regulation of autophagy, mitophagy and thereby mitochondrial function. (157,161,(165)(166)(167)(168)(169)(170)(171)(172)(173)(174)(175)(176)(177) Taken together, these examples provide strong support for the concept that autophagy plays a critical role in maintaining a normal lifespan and healthy neuronal aging, and that its decline is inexorably tied to age related pathologies ( Figure 5). (178) Degradation of dysfunctional mitochondria is carried out by the autophagy-lysosomal pathway.…”
Section: Mitochondrial -Lysosomal Dysfunction In Nddmentioning
confidence: 55%
“…33,38,43 These metabolic changes are reversible. 44 Like so called "starvation-diabetes," this condition may be benevolent and associated with longevity. 45 Also, "starvation-like" benevolent diabetes seems to be achieved only at high everyday doses and in some strains like C57BL/6NCr.…”
Section: Introductionmentioning
confidence: 99%
“…44 It may seem paradoxical that intermittent administration (by i.p.) is more effective than everyday administration (by oral gavash).…”
mentioning
confidence: 99%