Association of FOXO3A variation with human longevity confirmed in German centenarians.

Abstract:

:The human forkhead box O3A gene (FOXO3A) encodes an evolutionarily conserved key regulator of the insulin-IGF1 signaling pathway that is known to influence metabolism and lifespan in model organisms. A recent study described 3 SNPs in the FOXO3A gene that were statistically significantly associated with longevity in a discovery sample of long-lived men of Japanese ancestry [Willcox et al. (2008) Proc Natl Acad Sci USA 105:13987-13992]. However, this finding required replication in an independent population. Here, we have investigated 16 known FOXO3A SNPs in an extensive collection of 1,762 German centenarians/nonagenarians and younger controls and provide evidence that polymorphisms in this gene were indeed associated with the ability to attain exceptional old age. The FOXO3A association was considerably stronger in centenarians than in nonagenarians, highlighting the importance of centenarians for genetic longevity research. Our study extended the initial finding observed in Japanese men to women and indicates that both genders were likely to be equally affected by variation in FOXO3A. Replication in a French centenarian sample generated a trend that supported the previous results. Our findings confirmed the initial discovery in the Japanese sample and indicate FOXO3A as a susceptibility gene for prolonged survival in humans.

authors

Flachsbart F,Caliebe A,Kleindorp R,Blanché H,von Eller-Eberstein H,Nikolaus S,Schreiber S,Nebel A

doi

10.1073/pnas.0809594106

subject

Has Abstract

pub_date

2009-02-24 00:00:00

pages

2700-5

issue

8

eissn

0027-8424

issn

1091-6490

pii

0809594106

journal_volume

106

pub_type

杂志文章
  • Unilamellar vesicle formation and encapsulation by microfluidic jetting.

    abstract::Compartmentalization of biomolecules within lipid membranes is a fundamental requirement of living systems and an essential feature of many pharmaceutical therapies. However, applications of membrane-enclosed solutions of proteins, DNA, and other biologically active compounds have been limited by the difficulty of for...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0710875105

    authors: Stachowiak JC,Richmond DL,Li TH,Liu AP,Parekh SH,Fletcher DA

    更新日期:2008-03-25 00:00:00

  • Expression of alpha-thymosins in human tissues in normal and abnormal growth.

    abstract::Radioimmunoassays specific for the N and C termini of human prothymosin alpha and the N terminus of human parathymosin alpha were employed for the measurement of the levels of alpha-thymosins in human thymus, spleen, and liver during normal growth and intestine and breast in malignant growth. A differential expression...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.20.9504

    authors: Tsitsiloni OE,Stiakakis J,Koutselinis A,Gogas J,Markopoulos C,Yialouris P,Bekris S,Panoussopoulos D,Kiortsis V,Voelter W

    更新日期:1993-10-15 00:00:00

  • Hyphal development in Neurospora crassa: involvement of a two-component histidine kinase.

    abstract::Two-component signal transduction systems are most often found in prokaryotic organisms where they are responsible for mediating the cellular responses to many environmental stimuli. These systems are composed of an autophosphorylating histidine kinase and a response regulator. We have found evidence for the existence...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.8.3416

    authors: Alex LA,Borkovich KA,Simon MI

    更新日期:1996-04-16 00:00:00

  • Protein p53 and inducer-mediated erythroleukemia cell commitment to terminal cell division.

    abstract::Inducer-mediated murine erythroleukemia cell (MELC) differentiation provides a model for examining factors determining terminal cell differentiation. The nuclear protein, p53, has been implicated as a potential determinant of cell cycle progression and cell differentiation. In this study p53 content and synthesis, dur...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.19.5919

    authors: Shen DW,Real FX,DeLeo AB,Old LJ,Marks PA,Rifkind RA

    更新日期:1983-10-01 00:00:00

  • A DNA fragment with an alpha-phosphorothioate nucleotide at one end is asymmetrically blocked from digestion by exonuclease III and can be replicated in vivo.

    abstract::2'-Deoxyadenosine 5'-O-(1-thiotriphosphate) (dATP[alpha S]) was introduced into the 3' ends of DNA restriction fragments with Escherichia coli DNA polymerase I to give phosphorothioate internucleotide linkages. Such "capped" 3' ends were found to be resistant to exonuclease III digestion. Moreover, the resistance to d...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.12.7350

    authors: Putney SD,Benkovic SJ,Schimmel PR

    更新日期:1981-12-01 00:00:00

  • Consequences of reproductive barriers for genealogical discordance in the European corn borer.

    abstract::Speciation involves the origin of trait differences that limit or prevent gene exchange and ultimately results in daughter populations that form monophyletic or exclusive genetic groups. However, for recently diverged populations or species between which reproductive isolation is often incomplete, gene genealogies wil...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0502054102

    authors: Dopman EB,Pérez L,Bogdanowicz SM,Harrison RG

    更新日期:2005-10-11 00:00:00

  • C factor, a cell-surface-associated intercellular signaling protein, stimulates the cytoplasmic Frz signal transduction system in Myxococcus xanthus.

    abstract::C factor, an intercellular signaling protein, is required for aggregation and sporulation of the social bacterium, Myxococcus xanthus. We report that C factor, which normally is associated with the cell surface, provides input to the Frz signal transduction cascade. Elements of this cascade have sequence homology to b...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.7.2675

    authors: Søgaard-Andersen L,Kaiser D

    更新日期:1996-04-02 00:00:00

  • Effect of lysine methylation and other ATPase modulators on the active site of myosin subfragment 1.

    abstract::Many and diverse modifications of the myosin subfragment 1 (S-1) increase (modulate) its ATPase activity, including interaction of this particle with actin; a recent addition to these modifications is the extensive lysine modification of S-1 that seems prerequisite to crystallizing it for structure analysis. In this s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.18.8665

    authors: Bivin DB,Ue K,Khoroshev M,Morales M

    更新日期:1994-08-30 00:00:00

  • Prokaryotic algae associated with Australian proterozoic stromatolites.

    abstract::Five instances of association between distinctive stromatolites and blue-green algal nannofossils are recorded from a 100-m sequence of carbonate rocks about 1.6 x 10(9) years old, along the south side of Paradise Creek, northwestern Queensland, Australia. No eukaryotes were identified in any of these systematically l...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.9.2500

    authors: Licari GR,Cloud P

    更新日期:1972-09-01 00:00:00

  • Observation of an apparent first-order glass transition in ultrafragile Pt-Cu-P bulk metallic glasses.

    abstract::An experimental study of the configurational thermodynamics for a series of near-eutectic Pt80-x Cu x P20 bulk metallic glass-forming alloys is reported where 14 < x < 27. The undercooled liquid alloys exhibit very high fragility that increases as x decreases, resulting in...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1916371117

    authors: Na JH,Corona SL,Hoff A,Johnson WL

    更新日期:2020-02-11 00:00:00

  • Conscious recollection and the human hippocampal formation: evidence from positron emission tomography.

    abstract::We used positron emission tomography (PET) to examine the role of the hippocampal formation in implicit and explicit memory. Human volunteers studied a list of familiar words, and then they either provided the first word that came to mind in response to three-letter cues (implicit memory) or tried to recall studied wo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.1.321

    authors: Schacter DL,Alpert NM,Savage CR,Rauch SL,Albert MS

    更新日期:1996-01-09 00:00:00

  • A mutant alpha subunit of Gi2 induces neoplastic transformation of Rat-1 cells.

    abstract::In a recently discovered class of oncogenes, GTPase-inhibiting mutations constitutively activate alpha subunits of signal-transducing guanine nucleotide-binding proteins (G proteins). Somatic mutations in a subclass of endocrine tumors are found in the arginine-179 codon of the alpha subunit of Gi2 (alpha i2), creatin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.16.7031

    authors: Pace AM,Wong YH,Bourne HR

    更新日期:1991-08-15 00:00:00

  • Role of cyclophilin A in the uptake of HIV-1 by macrophages and T lymphocytes.

    abstract::Cyclophilins are a family of proteins that bind cyclosporin A (CsA) and possess peptidyl-prolyl cis-trans isomerase activity. In addition, they are secreted by activated cells and act in a cytokine-like manner, presumably via signaling through a cell surface cyclophilin receptor. More recently, host-derived cyclophili...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.4.1758

    authors: Sherry B,Zybarth G,Alfano M,Dubrovsky L,Mitchell R,Rich D,Ulrich P,Bucala R,Cerami A,Bukrinsky M

    更新日期:1998-02-17 00:00:00

  • Chemistry of acetylene on platinum (111) and (100) surfaces.

    abstract::An ultra-high vacuum experimental study of acetylene chemisorption on Pt(111) and Pt(100) and of the reaction of hydrogen with the acetylene adsorbate has established distinguishing features of carbon-hydrogen bond breaking and making processes as a function of pressure, temperature, and surface crystallography. The r...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.11.6571

    authors: Muetterties EL,Tasi MC,Kelemen SR

    更新日期:1981-11-01 00:00:00

  • The palmitoylated cysteine of the cytoplasmic tail of alpha 2A-adrenergic receptors confers subtype-specific agonist-promoted downregulation.

    abstract::Most guanine nucleotide binding protein (G protein)-coupled receptors have a conserved cysteine in the C-terminal cytoplasmic tail near the seventh transmembrane spanning region. This cysteine is known to be palmitoylated in rhodopsin, the beta 2-adrenergic receptor (beta 2AR) and the alpha 2A-adrenergic receptor (alp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.23.11178

    authors: Eason MG,Jacinto MT,Theiss CT,Liggett SB

    更新日期:1994-11-08 00:00:00

  • Energies and kinetics of radical pairs involving bacteriochlorophyll and bacteriopheophytin in bacterial reaction centers.

    abstract::Absorbance changes reflecting the formation of a transient radical-pair state, P(F), were measured in reaction centers from Rhodopseudomonas sphaeroides under conditions that blocked electron transfer to a later carrier (a quinone, Q). The temperature dependence of the absorbance changes suggests that P(F) is an equil...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.2.957

    authors: Shuvalov VA,Parson WW

    更新日期:1981-02-01 00:00:00

  • Photodegradation alleviates the lignin bottleneck for carbon turnover in terrestrial ecosystems.

    abstract::A mechanistic understanding of the controls on carbon storage and losses is essential for our capacity to predict and mitigate human impacts on the global carbon cycle. Plant litter decomposition is an important first step for carbon and nutrient turnover, and litter inputs and losses are essential in determining soil...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1516157113

    authors: Austin AT,Méndez MS,Ballaré CL

    更新日期:2016-04-19 00:00:00

  • Phenotypic and functional immaturity of human umbilical cord blood T lymphocytes.

    abstract::Successful implementation of bone marrow transplantation for hematopoietic reconstitution is limited by the lack of suitably HLA-matched donors and by the occurrence of graft-versus-host disease that frequently accompanies this procedure. Recent clinical reports have implied that the use of umbilical cord blood as a s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.21.10006

    authors: Harris DT,Schumacher MJ,Locascio J,Besencon FJ,Olson GB,DeLuca D,Shenker L,Bard J,Boyse EA

    更新日期:1992-11-01 00:00:00

  • X-ray structure of clotting factor IXa: active site and module structure related to Xase activity and hemophilia B.

    abstract::Hereditary deficiency of factor IXa (fIXa), a key enzyme in blood coagulation, causes hemophilia B, a severe X chromosome-linked bleeding disorder afflicting 1 in 30,000 males; clinical studies have identified nearly 500 deleterious variants. The x-ray structure of porcine fIXa described here shows the atomic origins ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.21.9796

    authors: Brandstetter H,Bauer M,Huber R,Lollar P,Bode W

    更新日期:1995-10-10 00:00:00

  • Phylogenetic profiles reveal evolutionary relationships within the "twilight zone" of sequence similarity.

    abstract::Inferring evolutionary relationships among highly divergent protein sequences is a daunting task. In particular, when pairwise sequence alignments between protein sequences fall <25% identity, the phylogenetic relationships among sequences cannot be estimated with statistical certainty. Here, we show that phylogenetic...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0803860105

    authors: Chang GS,Hong Y,Ko KD,Bhardwaj G,Holmes EC,Patterson RL,van Rossum DB

    更新日期:2008-09-09 00:00:00

  • The Drosophila Trpm channel mediates calcium influx during egg activation.

    abstract::Egg activation is the process in which mature oocytes are released from developmental arrest and gain competency for embryonic development. In Drosophila and other arthropods, eggs are activated by mechanical pressure in the female reproductive tract, whereas in most other species, eggs are activated by fertilization....

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1906967116

    authors: Hu Q,Wolfner MF

    更新日期:2019-09-17 00:00:00

  • Mast cells are critical for controlling the bacterial burden and the healing of infected wounds.

    abstract::Skin wound infections are a significant health problem, and antibiotic resistance is on the rise. Mast cells (MCs) have been shown to contribute to host-defense responses in certain bacterial infections, but their role in skin wound superinfection is unknown. We subjected 2 MC-deficient mouse strains to Pseudomonas ae...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1908816116

    authors: Zimmermann C,Troeltzsch D,Giménez-Rivera VA,Galli SJ,Metz M,Maurer M,Siebenhaar F

    更新日期:2019-10-08 00:00:00

  • Drosophila protein phosphatases 2A B' Wdb and Wrd regulate meiotic centromere localization and function of the MEI-S332 Shugoshin.

    abstract::Proper segregation of chromosomes in meiosis is essential to prevent miscarriages and birth defects. This requires that sister chromatids maintain cohesion at the centromere as cohesion is released on the chromatid arms when the homologs segregate at anaphase I. The Shugoshin proteins preserve centromere cohesion by p...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1718450114

    authors: Pinto BS,Orr-Weaver TL

    更新日期:2017-12-05 00:00:00

  • Cellular responses to Ca2+ from extracellular and intracellular sources are different as shown by simultaneous measurements of cytosolic Ca2+ and secretion from bovine chromaffin cells.

    abstract::Bovine adrenal medullary cells, cultured on quartz plates, were superfused with buffer to which pulses of stimulant were added. Cytosolic Ca2+ was measured by the fura-2 fluorescence method and the simultaneously released catecholamine was measured electrochemically. When stimulant concentrations were adjusted to give...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.24.9881

    authors: Kim KT,Westhead EW

    更新日期:1989-12-01 00:00:00

  • Karyophilic proteins: polypeptides synthesized in vitro accumulate in the nucleus on microinjection into the cytoplasm of amphibian oocytes.

    abstract::The specific nucleocytoplasmic compartmentalization of proteins has been examined for some major soluble acidic nuclear proteins in oocytes of different amphibia. Proteins synthesized and radioactively labeled by translation in vitro, by using mRNA from ovaries of the frog Xenopus laevis, were injected into the cytopl...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.17.5302

    authors: Dabauvalle MC,Franke WW

    更新日期:1982-09-01 00:00:00

  • Anti-inflammatory role in septic shock of pituitary adenylate cyclase-activating polypeptide receptor.

    abstract::Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two mediators synthesized by immune cells, specially under inflammatory and antigen stimulation conditions. Reports have shown that neuropeptides attenuate the deleterious consequences of septic shock both by down-re...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.012367999

    authors: Martinez C,Abad C,Delgado M,Arranz A,Juarranz MG,Rodriguez-Henche N,Brabet P,Leceta J,Gomariz RP

    更新日期:2002-01-22 00:00:00

  • The complete cDNA and deduced amino acid sequence of a type II mouse epidermal keratin of 60,000 Da: analysis of sequence differences between type I and type II keratins.

    abstract::We present the complete nucleotide and deduced amino acid sequences of a mouse epidermal keratin subunit of 60,000 Da. The keratin possesses a central alpha-helical domain of four tracts (termed 1A, 1B, 2A, and 2B) that can form coiled-coils, interspersed by short linker sequences, and has non-alpha-helical terminal d...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.18.5709

    authors: Steinert PM,Parry DA,Racoosin EL,Idler WW,Steven AC,Trus BL,Roop DR

    更新日期:1984-09-01 00:00:00

  • A newly discovered bacterium associated with parthenogenesis and a change in host selection behavior in parasitoid wasps.

    abstract::The symbiotic bacterium Wolbachia pipientis has been considered unique in its ability to cause multiple reproductive anomalies in its arthropod hosts. Here we report that an undescribed bacterium is vertically transmitted and associated with thelytokous parthenogenetic reproduction in Encarsia, a genus of parasitoid w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.221467498

    authors: Zchori-Fein E,Gottlieb Y,Kelly SE,Brown JK,Wilson JM,Karr TL,Hunter MS

    更新日期:2001-10-23 00:00:00

  • Infinitesimal generators and quasi-units in potential theory.

    abstract::The underlying structure is taken as a strongly superharmonic cone [unk], defined as a partially ordered abelian semigroup with identity 0 which admits a multiplication by nonnegative scalars and satisfies two fundamental axioms of a potentialtheoretic character. In terms of a fixed nonzero element e there is introduc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.7.2498

    authors: Arsove M,Leutwiler H

    更新日期:1975-07-01 00:00:00

  • High-temperature high-pressure phases of lithium from electron force field (eFF) quantum electron dynamics simulations.

    abstract::We recently developed the electron force field (eFF) method for practical nonadiabatic electron dynamics simulations of materials under extreme conditions and showed that it gave an excellent description of the shock thermodynamics of hydrogen from molecules to atoms to plasma, as well as the electron dynamics of the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1110322108

    authors: Kim H,Su JT,Goddard WA 3rd

    更新日期:2011-09-13 00:00:00