Abstract:
:Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruitflies; however, whether inhibition of mTOR signalling can extend lifespan in a mammalian species was unknown. Here we report that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age. On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males. The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility. Disease patterns of rapamycin-treated mice did not differ from those of control mice. In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis conducted near the median survival point. Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both. To our knowledge, these are the first results to demonstrate a role for mTOR signalling in the regulation of mammalian lifespan, as well as pharmacological extension of lifespan in both genders. These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases.
journal_name
Naturejournal_title
Natureauthors
Harrison DE,Strong R,Sharp ZD,Nelson JF,Astle CM,Flurkey K,Nadon NL,Wilkinson JE,Frenkel K,Carter CS,Pahor M,Javors MA,Fernandez E,Miller RAdoi
10.1038/nature08221subject
Has Abstractpub_date
2009-07-16 00:00:00pages
392-5issue
7253eissn
0028-0836issn
1476-4687pii
nature08221journal_volume
460pub_type
杂志文章相关文献
NATURE文献大全abstract::The Fanconi anaemia (FA) pathway repairs DNA damage caused by endogenous and chemotherapy-induced DNA crosslinks, and responds to replication stress1,2. Genetic inactivation of this pathway by mutation of genes encoding FA complementation group (FANC) proteins impairs development, prevents blood production and promote...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-1703-4
更新日期:2019-11-01 00:00:00
abstract::AFTER exposure to secretagogues the small intestine changes from a tissue that absorbs fluid and electrolyte from lumen to blood into a tissue that secretes electrolyte and fluid into the lumen(1-4). It has been shown that this secretion results from an increase in the passive Cl(-) permeability of the mucosal border,...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/279446a0
更新日期:1979-05-31 00:00:00
abstract::During platelet activation there is a major reorganization in the platelet cytoskeleton that accompanies a rapid change in platelet shape. Many of the events associated with activation are attributed to a rise in calcium concentration within the platelet cytoplasm. One direct consequence of the elevated calcium is the...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/317449a0
更新日期:1985-10-03 00:00:00
abstract::Mutations in the Schizosaccharomyces pombe cdc8 gene impair cytokinesis. Here we clone cdc8+ and find that it encodes a novel tropomyosin. Gene disruption results in lethal arrest of the cell cycle, but spore germination, cell growth, DNA replication and mitosis are all unaffected. Haploid cdc8 gene disruptants are re...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/360084a0
更新日期:1992-11-05 00:00:00
abstract::Transection of a sensory nerve in adults results in profound abnormalities in sensory perception, even if the severed nerve is surgically repaired to facilitate accurate nerve regeneration. In marked contrast, fewer perceptual errors follow nerve transection and surgical repair in children. The basis for this superior...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/381069a0
更新日期:1996-05-02 00:00:00
abstract::Activity-dependent change in the efficacy of transmission is a basic feature of many excitatory synapses in the central nervous system. The best understood postsynaptic modification involves a change in responsiveness of AMPAR (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor)-mediated currents follo...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35013064
更新日期:2000-05-25 00:00:00
abstract::Proteins are inherently plastic molecules, whose function often critically depends on excursions between different molecular conformations (conformers). However, a rigorous understanding of the relation between a protein's structure, dynamics and function remains elusive. This is because many of the conformers on its ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10349
更新日期:2011-08-21 00:00:00
abstract::Constructing agents with planning capabilities has long been one of the main challenges in the pursuit of artificial intelligence. Tree-based planning methods have enjoyed huge success in challenging domains, such as chess1 and Go2, where a perfect simulator is available. However, in real-world problems, the dynamics ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-03051-4
更新日期:2020-12-01 00:00:00
abstract::Lignin is a complex polymer of phenylpropanoid subunits. It is an essential component of woody tissue, to which it imparts structural rigidity. Lignin is remarkably resistant to degradation by most microbes; nevertheless, a few species of white-rot fungi are able to catalyse its oxidation to CO2. Its biodegradation is...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/326520a0
更新日期:1987-04-02 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/d41586-018-07366-1
更新日期:2018-11-01 00:00:00
abstract::The origins of religion and of complex societies represent evolutionary puzzles1-8. The 'moralizing gods' hypothesis offers a solution to both puzzles by proposing that belief in morally concerned supernatural agents culturally evolved to facilitate cooperation among strangers in large-scale societies9-13. Although pr...
journal_title:Nature
pub_type: 历史文章,杂志文章
doi:10.1038/s41586-019-1043-4
更新日期:2019-04-01 00:00:00
abstract::Maize smut caused by the fungus Ustilago maydis is a widespread disease characterized by the development of large plant tumours. U. maydis is a biotrophic pathogen that requires living plant tissue for its development and establishes an intimate interaction zone between fungal hyphae and the plant plasma membrane. U. ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10454
更新日期:2011-10-05 00:00:00
abstract::Transition-metal perovskite oxides exhibit a wide range of extraordinary but imperfectly understood phenomena. The best known examples are high-temperature superconductivity in copper oxides, and colossal magnetoresistance in manganese oxides ('manganites'). All of these materials undergo a range of order-disorder tra...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/416518a
更新日期:2002-04-04 00:00:00
abstract::The gene encoding the large-T protein of polyoma virus (plt), the E1A genes of adenoviruses, the viral myc gene (v-myc) or rearranged forms of the cellular c-myc gene confer on rat embryo fibroblast (REF) cells in primary culture a series of new properties ('immortality', reduced serum requirement and sensitivity to t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/314277a0
更新日期:1985-03-21 00:00:00
abstract::A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or setpoint viral loads a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07469
更新日期:2009-01-01 00:00:00
abstract::Thomas et al. argue, contrary to Sala et al. that climate change poses an equal or greater threat to global biodiversity than land-use change. We contest this claim, however, on the grounds that Thomas et al. incorrectly apply species-area relationships. ...
journal_title:Nature
pub_type: 评论,杂志文章
doi:10.1038/nature02717
更新日期:2004-07-01 00:00:00
abstract::Enhancers are DNA sequences that stimulate transcription from eukaryotic promoters. This stimulatory effect can be exerted over large distances and from a position either 5' or 3' of a promoter. Enhancers have been found in the genomes of many viruses, and in some cellular genes such as those encoding immunoglobulin h...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/322383a0
更新日期:1986-07-24 00:00:00
abstract::Deuterostomes are a remarkably diverse super-phylum, including not only the chordates (to which we belong) but groups as disparate as the echinoderms and the hemichordates. The phylogeny of deuterostomes is now achieving some degree of stability, especially on account of new molecular data, but this leaves as conjectu...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature02648
更新日期:2004-07-22 00:00:00
abstract::Symbolic arithmetic is fundamental to science, technology and economics, but its acquisition by children typically requires years of effort, instruction and drill. When adults perform mental arithmetic, they activate nonsymbolic, approximate number representations, and their performance suffers if this nonsymbolic sys...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature05850
更新日期:2007-05-31 00:00:00
abstract::Normal cellular function requires that organelles be positioned in specific locations. The direction in which molecular motors move organelles is based in part on the polarity of microtubules and actin filaments. However, this alone does not determine the intracellular destination of organelles. For example, the yeast...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01453
更新日期:2003-03-06 00:00:00
abstract::Recognition of an avirulent pathogen triggers the rapid production of the reactive oxygen intermediates superoxide (O2-) and hydrogen peroxide (H2O2). This oxidative burst drives crosslinking of the cell wall, induces several plant genes involved in cellular protection and defence, and is necessary for the initiation ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/29087
更新日期:1998-08-06 00:00:00
abstract::Novel biochemical processes using magnetic particles have been automated to provide a robotic system to perform processes for large-scale shotgun sequencing. ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/362569a0
更新日期:1993-04-08 00:00:00
abstract::During embryogenesis, body pattern is established in a stepwise process. After specification of the body axis, the embryo is subdivided into smaller units. Within these units, a diverse array of cell types is then generated. The subdivisions of the Drosophila embryo, called parasegments, are defined by the interface b...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/360347a0
更新日期:1992-11-26 00:00:00
abstract::The extension of growing season at high northern latitudes seems increasingly clear from satellite observations of vegetation extent and duration. This extension is also thought to explain the observed increase in amplitude of seasonal variations in atmospheric CO2 concentration. Increased plant respiration and photos...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35015049
更新日期:2000-06-08 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 评论,新闻
doi:10.1038/d41586-018-07165-8
更新日期:2018-11-01 00:00:00
abstract::Rapid warming over the past 50 years on the Antarctic Peninsula is associated with the collapse of a number of ice shelves and accelerating glacier mass loss. In contrast, warming has been comparatively modest over West Antarctica and significant changes have not been observed over most of East Antarctica, suggesting ...
journal_title:Nature
pub_type: 历史文章,杂志文章
doi:10.1038/nature11391
更新日期:2012-09-06 00:00:00
abstract::In this Letter, Supplementary Fig. 1 was missing. This error has been corrected online. ...
journal_title:Nature
pub_type: 已发布勘误
doi:10.1038/s41586-019-1207-2
更新日期:2019-05-01 00:00:00
abstract::Laboratory measurements of sound velocities of high-pressure minerals provide crucial information on the composition and constitution of the deep mantle via comparisons with observed seismic velocities. Calcium silicate (CaSiO3) perovskite (CaPv) is a high-pressure phase that occurs at depths greater than about 560 ki...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-018-0816-5
更新日期:2019-01-01 00:00:00
abstract::Seismological observations have revealed the existence of low-velocity and high-attenuation zones above the discontinuity at 410 km depth, at the base of the Earth's upper mantle. It has been suggested that a small amount of melt could be responsible for such anomalies. The density of silicate melt under dry condition...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04352
更新日期:2006-01-12 00:00:00
abstract::HLA class II molecules are a highly polymorphic family of dimeric cell-surface proteins primarily involved in regulating T-cell responses to extrinsic antigens. To define regions of class II molecules involved in T-cell recognition, we have now compared sequences of three HLA DR beta cDNA clones obtained from cells th...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/317166a0
更新日期:1985-09-12 00:00:00