Ageing: A midlife longevity drug?

Nature (Impact Factor: 42.35). 08/2009; 460(7253):331-2. DOI: 10.1038/460331a
Source: PubMed

ABSTRACT The small molecule rapamycin, already approved for clinical use for various human disorders, has been found to significantly increase lifespan in mice. Is this a step towards an anti-ageing drug for people?

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    ABSTRACT: TOR is involved in aging in a wide range of species from yeast to mammals. Here we show that, after overnight fasting, mTOR activity is higher in the livers of 28 months old female mice compared with middle-aged mice. Taken together with previous reports, our data predict that the life-extending effect of calorie restriction (CR) may be diminished, if CR is started in very old age. In contrast, rapamycin is known to be effective, even when started late in life.
    Cell cycle (Georgetown, Tex.) 09/2014; 13(17):2656-2659. DOI:10.4161/15384101.2014.949150 · 5.01 Impact Factor
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    ABSTRACT: The mechanistic target of rapamycin (mTOR) is a highly conserved protein that regulates growth and proliferation in response to environmental and hormonal cues. Broadly speaking, organisms are constantly faced with the challenge of interpreting their environment and making a decision between "grow or do not grow." mTOR is a major component of the network that makes this decision at the cellular level and, to some extent, the tissue and organismal level as well. Although overly simplistic, this framework can be useful when considering the myriad functions ascribed to mTOR and the pleiotropic phenotypes associated with genetic or pharmacological modulation of mTOR signaling. In this review, I will consider mTOR function in this context and attempt to summarize and interpret the growing body of literature demonstrating interesting and varied effects of mTOR inhibitors. These include robust effects on a multitude of age-related parameters and pathologies, as well as several other processes not obviously linked to aging or age-related disease.
    11/2013; 2013:849186. DOI:10.1155/2013/849186
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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 three-fold 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 to rapamycin, and the pattern of expression of hepatic genes involved in xenobiotic metabolism is also quite distinct in rapamycin-treated and diet restricted mice, suggesting that these two interventions for extending mouse lifespan differ in many respects. This article is protected by copyright. All rights reserved.
    Aging cell 12/2013; DOI:10.1111/acel.12194 · 5.94 Impact Factor

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