Gene expression analysis of mTOR pathway: association with human longevity.

Abstract:

:mTOR signalling is implicated in the development of disease and in lifespan extension in model organisms. This pathway has been associated with human diseases such as diabetes and cancer, but has not been investigated for its impact on longevity per se. Here, we investigated whether transcriptional variation within the mTOR pathway is associated with human longevity using whole-blood samples from the Leiden Longevity Study. This is a unique cohort of Dutch families with extended survival across generations, decreased morbidity and beneficial metabolic profiles in middle-age. By comparing mRNA levels of nonagenarians and middle-aged controls, the mTOR signalling gene set was found to associate with old age (P = 4.6 × 10(-7)). Single gene analysis showed that seven of 40 mTOR pathway genes had a significant differential expression of at least 5%. Of these, the RPTOR (Raptor) gene was found to be differentially expressed also when the offspring of nonagenarians was compared with their spouses, indicating association with familial longevity in middle-age. This association was not explained by variation between the groups in the prevalence of type 2 diabetes and cancer or glucose levels. Thus, the mTOR pathway not only plays a role in the regulation of disease and aging in animal models, but also in human health and longevity.

journal_name

Aging Cell

journal_title

Aging cell

authors

Passtoors WM,Beekman M,Deelen J,van der Breggen R,Maier AB,Guigas B,Derhovanessian E,van Heemst D,de Craen AJ,Gunn DA,Pawelec G,Slagboom PE

doi

10.1111/acel.12015

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

24-31

issue

1

eissn

1474-9718

issn

1474-9726

journal_volume

12

pub_type

杂志文章
  • Caenorhabditis elegans integrates food and reproductive signals in lifespan determination.

    abstract::Dietary restriction extends lifespan and inhibits reproduction in many species. In Caenorhabditis elegans, inhibiting reproduction by germline removal extends lifespan. Therefore, we asked whether the effect of dietary restriction on lifespan might proceed via changes in the activity of the germline. We found that die...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2007.00327.x

    authors: Crawford D,Libina N,Kenyon C

    更新日期:2007-10-01 00:00:00

  • Transcription factor networks in aged naïve CD4 T cells bias lineage differentiation.

    abstract::With reduced thymic activity, the population of naïve T cells in humans is maintained by homeostatic proliferation throughout adult life. In young adults, naïve CD4 T cells have enormous proliferative potential and plasticity to differentiate into different lineages. Here, we explored whether naïve CD4 T-cell aging is...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12957

    authors: Hu B,Li G,Ye Z,Gustafson CE,Tian L,Weyand CM,Goronzy JJ

    更新日期:2019-08-01 00:00:00

  • Pharmacological maintenance of protein homeostasis could postpone age-related disease.

    abstract::Over the last 10 years, various screens of small molecules have been conducted to find long sought interventions in aging. Most of these studies were performed in invertebrates but the demonstration of pharmacological lifespan extension in the mouse has created considerable excitement. Since aging is a common risk fac...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2012.00789.x

    authors: Alavez S,Lithgow GJ

    更新日期:2012-04-01 00:00:00

  • Accelerated food source location in aging Drosophila.

    abstract::Adequate energy stores are essential for survival, and sophisticated neuroendocrine mechanisms evolved to stimulate foraging in response to nutrient deprivation. Food search behavior is usually investigated in young animals, and it is not known how aging alters this behavior. To address this question in Drosophila mel...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12361

    authors: Egenriether SM,Chow ES,Krauth N,Giebultowicz JM

    更新日期:2015-10-01 00:00:00

  • Effects of aging and gender on the spatial organization of nuclei in single human skeletal muscle cells.

    abstract::The skeletal muscle fibre is a syncitium where each myonucleus regulates the gene products in a finite volume of the cytoplasm, i.e., the myonuclear domain (MND). We analysed aging- and gender-related effects on myonuclei organization and the MND size in single muscle fibres from six young (21-31 years) and nine old m...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2010.00594.x

    authors: Cristea A,Qaisar R,Edlund PK,Lindblad J,Bengtsson E,Larsson L

    更新日期:2010-10-01 00:00:00

  • Demographic window to aging in the wild: constructing life tables and estimating survival functions from marked individuals of unknown age.

    abstract::Summary We address the problem of establishing a survival schedule for wild populations. A demographic key identity is established, leading to a method whereby age-specific survival and mortality can be deduced from a marked cohort life table established for individuals that are randomly sampled at unknown age and mar...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9728.2004.00096.x

    authors: Müller HG,Wang JL,Carey JR,Caswell-Chen EP,Chen C,Papadopoulos N,Yao F

    更新日期:2004-06-01 00:00:00

  • Early removal of senescent cells protects retinal ganglion cells loss in experimental ocular hypertension.

    abstract::Experimental ocular hypertension induces senescence of retinal ganglion cells (RGCs) that mimics events occurring in human glaucoma. Senescence-related chromatin remodeling leads to profound transcriptional changes including the upregulation of a subset of genes that encode multiple proteins collectively referred to a...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.13089

    authors: Rocha LR,Nguyen Huu VA,Palomino La Torre C,Xu Q,Jabari M,Krawczyk M,Weinreb RN,Skowronska-Krawczyk D

    更新日期:2020-02-01 00:00:00

  • Unlike dietary restriction, rapamycin fails to extend lifespan and reduce transcription stress in progeroid DNA repair-deficient mice.

    abstract::Dietary restriction (DR) and rapamycin extend healthspan and life span across multiple species. We have recently shown that DR in progeroid DNA repair-deficient mice dramatically extended healthspan and trippled life span. Here, we show that rapamycin, while significantly lowering mTOR signaling, failed to improve lif...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.13302

    authors: Birkisdóttir MB,Jaarsma D,Brandt RMC,Barnhoorn S,van Vliet N,Imholz S,van Oostrom CT,Nagarajah B,Portilla Fernández E,Roks AJM,Elgersma Y,van Steeg H,Ferreira JA,Pennings JLA,Hoeijmakers JHJ,Vermeij WP,Dollé MET

    更新日期:2021-01-23 00:00:00

  • Age-related sensitivity to endotoxin-induced liver inflammation: Implication of inflammasome/IL-1β for steatohepatitis.

    abstract::Aging is associated with increased vulnerability to inflammatory challenge. However, the effects of altered inflammatory response on the metabolic status of tissues or organs are not well documented. In this study, we present evidence demonstrating that lipopolysaccharide (LPS)-induced upregulation of the inflammasome...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12305

    authors: Chung KW,Lee EK,Kim DH,An HJ,Kim ND,Im DS,Lee J,Yu BP,Chung HY

    更新日期:2015-08-01 00:00:00

  • Methylation of ELOVL2 gene as a new epigenetic marker of age.

    abstract::The discovery of biomarkers able to predict biological age of individuals is a crucial goal in aging research. Recently, researchers' attention has turn toward epigenetic markers of aging. Using the Illumina Infinium HumanMethylation450 BeadChip on whole blood DNA from a small cohort of 64 subjects of different ages, ...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12005

    authors: Garagnani P,Bacalini MG,Pirazzini C,Gori D,Giuliani C,Mari D,Di Blasio AM,Gentilini D,Vitale G,Collino S,Rezzi S,Castellani G,Capri M,Salvioli S,Franceschi C

    更新日期:2012-12-01 00:00:00

  • An altered redox balance mediates the hypersensitivity of Cockayne syndrome primary fibroblasts to oxidative stress.

    abstract::Cockayne syndrome (CS) is a rare hereditary multisystem disease characterized by neurological and development impairment, and premature aging. Cockayne syndrome cells are hypersensitive to oxidative stress, but the molecular mechanisms involved remain unresolved. Here we provide the first evidence that primary fibrobl...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2012.00815.x

    authors: Pascucci B,Lemma T,Iorio E,Giovannini S,Vaz B,Iavarone I,Calcagnile A,Narciso L,Degan P,Podo F,Roginskya V,Janjic BM,Van Houten B,Stefanini M,Dogliotti E,D'Errico M

    更新日期:2012-06-01 00:00:00

  • Comparative transcriptomics across 14 Drosophila species reveals signatures of longevity.

    abstract::Lifespan varies dramatically among species, but the biological basis is not well understood. Previous studies in model organisms revealed the importance of nutrient sensing, mTOR, NAD/sirtuins, and insulin/IGF1 signaling in lifespan control. By studying life-history traits and transcriptomes of 14 Drosophila species d...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12740

    authors: Ma S,Avanesov AS,Porter E,Lee BC,Mariotti M,Zemskaya N,Guigo R,Moskalev AA,Gladyshev VN

    更新日期:2018-08-01 00:00:00

  • Aging exacerbates hypertension-induced cerebral microhemorrhages in mice: role of resveratrol treatment in vasoprotection.

    abstract::Recent studies demonstrate that aging exacerbates hypertension-induced cognitive decline, but the specific age-related mechanisms remain elusive. Cerebral microhemorrhages (CMHs) are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function. To determine whether a...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12315

    authors: Toth P,Tarantini S,Springo Z,Tucsek Z,Gautam T,Giles CB,Wren JD,Koller A,Sonntag WE,Csiszar A,Ungvari Z

    更新日期:2015-06-01 00:00:00

  • Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.

    abstract::Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduc...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12327

    authors: Golegaonkar S,Tabrez SS,Pandit A,Sethurathinam S,Jagadeeshaprasad MG,Bansode S,Sampathkumar SG,Kulkarni MJ,Mukhopadhyay A

    更新日期:2015-06-01 00:00:00

  • Smurf2-mediated ubiquitination and degradation of Id1 regulates p16 expression during senescence.

    abstract::The inhibitor of differentiation or DNA binding (Id) family of transcription regulators plays an important role in cell proliferation, differentiation, and senescence. However, regulation of Id expression during these processes is poorly understood. Id proteins are known to undergo rapid turnover mediated by the ubiqu...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2011.00746.x

    authors: Kong Y,Cui H,Zhang H

    更新日期:2011-12-01 00:00:00

  • Some highlights of research on aging with invertebrates, 2008.

    abstract::This annual review focuses on invertebrate model organisms, which shed light on new mechanisms in aging and provide excellent systems for in-depth analysis. This year, the first quantitative estimate of evolutionary conservation of genetic effects on lifespan has pointed to the key importance of genes involved in prot...

    journal_title:Aging cell

    pub_type: 杂志文章,评审

    doi:10.1111/j.1474-9726.2008.00415.x

    authors: Partridge L

    更新日期:2008-10-01 00:00:00

  • Uncovering the cellular and molecular changes in tendon stem/progenitor cells attributed to tendon aging and degeneration.

    abstract::Although the link between altered stem cell properties and tissue aging has been recognized, the molecular and cellular processes of tendon aging have not been elucidated. As tendons contain stem/progenitor cells (TSPC), we investigated whether the molecular and cellular attributes of TSPC alter during tendon aging an...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12124

    authors: Kohler J,Popov C,Klotz B,Alberton P,Prall WC,Haasters F,Müller-Deubert S,Ebert R,Klein-Hitpass L,Jakob F,Schieker M,Docheva D

    更新日期:2013-12-01 00:00:00

  • Genome-wide linkage analysis for human longevity: Genetics of Healthy Aging Study.

    abstract::Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that ha...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12039

    authors: Beekman M,Blanché H,Perola M,Hervonen A,Bezrukov V,Sikora E,Flachsbart F,Christiansen L,De Craen AJ,Kirkwood TB,Rea IM,Poulain M,Robine JM,Valensin S,Stazi MA,Passarino G,Deiana L,Gonos ES,Paternoster L,Sørensen TI

    更新日期:2013-04-01 00:00:00

  • Neuronal expression of a single-subunit yeast NADH-ubiquinone oxidoreductase (Ndi1) extends Drosophila lifespan.

    abstract::The 'rate of living' theory predicts that longevity should be inversely correlated with the rate of mitochondrial respiration. However, recent studies in a number of model organisms, including mice, have reported that interventions that retard the aging process are, in fact, associated with an increase in mitochondria...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2010.00546.x

    authors: Bahadorani S,Cho J,Lo T,Contreras H,Lawal HO,Krantz DE,Bradley TJ,Walker DW

    更新日期:2010-04-01 00:00:00

  • Heterochronic parabiosis: historical perspective and methodological considerations for studies of aging and longevity.

    abstract::Pairing two animals in parabiosis to test for systemic or circulatory factors from one animal affecting the other animal has been used in scientific studies for at least 150 years. These studies have led to advances in fields as diverse as endocrinology, immunology, and oncology. A variation on the technique, heteroch...

    journal_title:Aging cell

    pub_type: 杂志文章,评审

    doi:10.1111/acel.12065

    authors: Conboy MJ,Conboy IM,Rando TA

    更新日期:2013-06-01 00:00:00

  • Lgr5⁺ amacrine cells possess regenerative potential in the retina of adult mice.

    abstract::Current knowledge indicates that the adult mammalian retina lacks regenerative capacity. Here, we show that the adult stem cell marker, leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), is expressed in the retina of adult mice. Lgr5(+) cells are generated at late stages of retinal development and exh...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12346

    authors: Chen M,Tian S,Glasgow NG,Gibson G,Yang X,Shiber CE,Funderburgh J,Watkins S,Johnson JW,Schuman JS,Liu H

    更新日期:2015-08-01 00:00:00

  • The extreme longevity of Arctica islandica is associated with increased peroxidation resistance in mitochondrial membranes.

    abstract::The deleterious reactive carbonyls released upon oxidation of polyunsaturated fatty acids in biological membranes are believed to foster cellular aging. Comparative studies in mammals and birds have shown that the susceptibility to peroxidation of membrane lipids peroxidation index (PI) is negatively correlated with l...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2012.00847.x

    authors: Munro D,Blier PU

    更新日期:2012-10-01 00:00:00

  • Amyloid-beta 1-40 is associated with alterations in NG2+ pericyte population ex vivo and in vitro.

    abstract::The population of brain pericytes, a cell type important for vessel stability and blood brain barrier function, has recently been shown altered in patients with Alzheimer's disease (AD). The underlying reason for this alteration is not fully understood, but progressive accumulation of the AD characteristic peptide amy...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12728

    authors: Schultz N,Brännström K,Byman E,Moussaud S,Nielsen HM,Netherlands Brain Bank.,Olofsson A,Wennström M

    更新日期:2018-06-01 00:00:00

  • Dietary restriction of rodents decreases aging rate without affecting initial mortality rate -- a meta-analysis.

    abstract::Dietary restriction (DR) extends lifespan in multiple species from various taxa. This effect can arise via two distinct but not mutually exclusive ways: a change in aging rate and/or vulnerability to the aging process (i.e. initial mortality rate). When DR affects vulnerability, this lowers mortality instantly, wherea...

    journal_title:Aging cell

    pub_type: 杂志文章,meta分析

    doi:10.1111/acel.12061

    authors: Simons MJ,Koch W,Verhulst S

    更新日期:2013-06-01 00:00:00

  • Oestradiol or genistein rescues neurons from amyloid beta-induced cell death by inhibiting activation of p38.

    abstract::Oestrogenic compounds have been postulated as neuroprotective agents. This prompted us to investigate their mechanism action in neurons in primary culture. Cells were pretreated with physiological concentrations of 17-beta estradiol (0.2 nm) or with nutritionally relevant concentrations of genistein (0.5 microm), and ...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2007.00356.x

    authors: Vallés SL,Borrás C,Gambini J,Furriol J,Ortega A,Sastre J,Pallardó FV,Viña J

    更新日期:2008-01-01 00:00:00

  • Naturally occurring genetic variation in the age-specific immune response of Drosophila melanogaster.

    abstract::Immunosenescence, the age-related decline in immune response, is a well-known consequence of aging. To date, most studies of age-related changes in immune response focused on the cellular and physiological bases of this decline; we have virtually no understanding of the genetic basis of age-related changes in the immu...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2006.00219.x

    authors: Lesser KJ,Paiusi IC,Leips J

    更新日期:2006-08-01 00:00:00

  • Nuclear envelope dysfunction and its contribution to the aging process.

    abstract::The nuclear envelope (NE) is the central organizing unit of the eukaryotic cell serving as a genome protective barrier and mechanotransduction interface between the cytoplasm and the nucleus. The NE is mainly composed of a nuclear lamina and a double membrane connected at specific points where the nuclear pore complex...

    journal_title:Aging cell

    pub_type: 杂志文章,评审

    doi:10.1111/acel.13143

    authors: Martins F,Sousa J,Pereira CD,da Cruz E Silva OAB,Rebelo S

    更新日期:2020-05-01 00:00:00

  • Amyloid-beta(1-42) alters structure and function of retinal pigmented epithelial cells.

    abstract::Age-related macular degeneration (AMD) is characterized by the formation of drusen, extracellular deposits associated with atrophy of the retinal pigmented epithelium (RPE), disturbance of the transepithelial barrier and photoreceptor death. Amyloid-beta (Abeta) is present in drusen but its role during AMD remains unk...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2009.00456.x

    authors: Bruban J,Glotin AL,Dinet V,Chalour N,Sennlaub F,Jonet L,An N,Faussat AM,Mascarelli F

    更新日期:2009-04-01 00:00:00

  • The load of short telomeres, estimated by a new method, Universal STELA, correlates with number of senescent cells.

    abstract::Short telomeres are thought to trigger senescence, most likely through a single - or a group of few - critically shortened telomeres. Such short telomeres are thought to result from a combination of gradual linear shortening resulting from the end replication problem, reflecting the division history of the cell, super...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2010.00568.x

    authors: Bendix L,Horn PB,Jensen UB,Rubelj I,Kolvraa S

    更新日期:2010-06-01 00:00:00

  • Acquired temperature-sensitive paralysis as a biomarker of declining neuronal function in aging Drosophila.

    abstract::General locomotor activity decreases with normal aging in animals and could be partially explained by decreases in neuronal function. Voltage-gated Na(+) channels are essential in initiating and propagating rapid electrical impulses underlying normal locomotor activity and behavior in animals. Isolation of mutations c...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2008.00368.x

    authors: Reenan RA,Rogina B

    更新日期:2008-03-01 00:00:00