target of rapamycin
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JCI - Rapamycin extends murine lifespan but has limited effects on aging

JCI - Rapamycin extends murine lifespan but has limited effects on aging | target of rapamycin | Scoop.it

Aging is a major risk factor for a large number of disorders and functional impairments. Therapeutic targeting of the aging process may therefore represent an innovative strategy in the quest for novel and broadly effective treatments against age-related diseases. The recent report of lifespan extension in mice treated with the FDA-approved mTOR inhibitor rapamycin represented the first demonstration of pharmacological extension of maximal lifespan in mammals. Longevity effects of rapamycin may, however, be due to rapamycin’s effects on specific life-limiting pathologies, such as cancers, and it remains unclear if this compound actually slows the rate of aging in mammals. Here, we present results from a comprehensive, large-scale assessment of a wide range of structural and functional aging phenotypes, which we performed to determine whether rapamycin slows the rate of aging in male C57BL/6J mice. While rapamycin did extend lifespan, it ameliorated few studied aging phenotypes. A subset of aging traits appeared to be rescued by rapamycin. Rapamycin, however, had similar effects on many of these traits in young animals, indicating that these effects were not due to a modulation of aging, but rather related to aging-independent drug effects. Therefore, our data largely dissociate rapamycin’s longevity effects from effects on aging itself.

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Pharmacophore Modeling, Homology Modeling, and in silico Screening Reveal Mammalian Target of Rapamycin Inhibitory Activities for Sotalol, Glyburide, Metipranolol, Sulfamethizole, Glipizide, and Pi...

Pharmacophore Modeling, Homology Modeling, and in silico Screening Reveal Mammalian Target of Rapamycin Inhibitory Activities for Sotalol, Glyburide, Metipranolol, Sulfamethizole, Glipizide, and Pi... | target of rapamycin | Scoop.it
Available online 13 March 2013
Publication year: 2013
Source:Journal of Molecular Graphics and Modelling

Mammalian target of rapamycin (mTOR) is a serine/threonine kinase and member of the PI3K-related kinase (PIKK) family.

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The Ups and Downs of Rapamycin

As if taking a cancer drug was not bad enough, there has been a lot of research being conducted lately about whether or not a cancer treatment causes a diabetic like symptoms and problems in those who do not have diabetes.
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mTORC1 Status Dictates Tumor Response to Targeted Therapeutics

"Genomics has revolutionized and personalized our approach to cancer therapy, with clinical trials now frequently involving patient stratification based on tumor genotype. Rational drug design specifically targeting the most common genetic events and aberrantly regulated pathways in human cancers makes this approach possible. However, our understanding of the wiring of oncogenic signaling networks and the key downstream effectors driving human cancers is incomplete, limiting our ability to predict clinical responses or identify mechanisms of resistance to targeted therapeutics. Recent studies in independent cancer lineages driven by distinct oncogenic signaling events point to a common downstream target, the mammalian (or mechanistic) target of rapamycin complex 1 (mTORC1), which dictates the cellular and clinical response to pathway-specific inhibitors. mTORC1 is a highly integrated signaling node that promotes anabolic cell growth and proliferation and lies downstream of multiple oncogenes and tumor suppressors, including those influencing the PI3K-Akt and RAS-RAF-MEK-ERK pathways. Studies are now suggesting that to effectively target the major oncogenic signaling pathway in a given tumor, mTORC1 must be inhibited, and that its sustained activation is a major mechanism of resistance to such targeted therapies."


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Cancer Commons's curator insight, September 25, 2013 4:57 PM

Kelsey I, Manning BD. Sci. Signal. Sep 24, 2013.

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Rapamycin: Limited anti-aging effects | ScienceBlog.com

Rapamycin: Limited anti-aging effects | ScienceBlog.com | target of rapamycin | Scoop.it
Lifespan measures alone are not a reliable indicator of anti-aging effects,” emphasises Ehninger. “This makes the search for anti-aging medicines tedious, but it is also very promising, because such substances could open up ...

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