High-fat diet protects the blood-brain barrier in an Alzheimer's disease mouse model.

Abstract:

:Type 2 diabetes (T2D) is associated with increased risk of Alzheimer's disease (AD). There is evidence for impaired blood-brain barrier (BBB) in both diseases, but its role in the interplay between them is not clear. Here, we investigated the effects of high-fat diet (HFD), a model for T2D, on the Tg2576 mouse model of AD, in regard to BBB function. We showed that HFD mice had higher weight, more insulin resistance, and higher serum HDL cholesterol levels, primarily in Tg2576 mice, which also had higher brain lipids content. In terms of behavior, Tg2576 HFD mice were less active and more anxious, but had better learning in the Morris Water Maze compared to Tg2576 on regular diet. HFD had no effect on the level of amyloid beta 1-42 in the cortex of Tg2576 mice, but increased the transcription level of insulin receptor in the hippocampus. Tg2576 mice on regular diet demonstrated more BBB disruption at 8 and 12 months accompanied by larger lateral ventricles volume in contrast to Tg2576 HFD mice, whose BBB leakage and ventricular volume were similar to wild-type (WT) mice. Our results suggest that in AD, HFD may promote better cognitive function through improvements of BBB function and of brain atrophy but not of amyloid beta levels. Lipid metabolism in the CNS and peripheral tissues and brain insulin signaling may underlie this protection.

journal_name

Aging Cell

journal_title

Aging cell

authors

Elhaik Goldman S,Goez D,Last D,Naor S,Liraz Zaltsman S,Sharvit-Ginon I,Atrakchi-Baranes D,Shemesh C,Twitto-Greenberg R,Tsach S,Lotan R,Leikin-Frenkel A,Shish A,Mardor Y,Schnaider Beeri M,Cooper I

doi

10.1111/acel.12818

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

e12818

issue

5

eissn

1474-9718

issn

1474-9726

journal_volume

17

pub_type

杂志文章
  • 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

  • A role for the Werner syndrome protein in epigenetic inactivation of the pluripotency factor Oct4.

    abstract::Werner syndrome (WS) is an autosomal recessive disorder, the hallmarks of which are premature aging and early onset of neoplastic diseases (Orren, 2006; Bohr, 2008). The gene, whose mutation underlies the WS phenotype, is called WRN. The protein encoded by the WRN gene, WRNp, has DNA helicase activity (Gray et al., 19...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2010.00585.x

    authors: Smith JA,Ndoye AM,Geary K,Lisanti MP,Igoucheva O,Daniel R

    更新日期:2010-08-01 00:00:00

  • Hot topics in stem cells and self-renewal: 2010.

    abstract::In many tissues, mammalian aging is associated with a decline in the replicative and functional capacity of somatic stem cells and other self-renewing compartments. Understanding the basis of this decline is a major goal of aging research. In particular, therapeutic approaches to ameliorate or reverse the age-associat...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2010.00592.x

    authors: Sharpless NE

    更新日期:2010-08-01 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

  • Characterization of the direct targets of FOXO transcription factors throughout evolution.

    abstract::FOXO transcription factors (FOXOs) are central regulators of lifespan across species, yet they also have cell-specific functions, including adult stem cell homeostasis and immune function. Direct targets of FOXOs have been identified genome-wide in several species and cell types. However, whether FOXO targets are spec...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12479

    authors: Webb AE,Kundaje A,Brunet A

    更新日期:2016-08-01 00:00:00

  • Identification of genetic determinants of IGF-1 levels and longevity among mouse inbred strains.

    abstract::The IGF-1 signaling pathway plays an important role in regulating longevity. To identify the genetic loci and genes that regulate plasma IGF-1 levels, we intercrossed MRL/MpJ and SM/J, inbred mouse strains that differ in IGF-1 levels. Quantitative trait loci (QTL) analysis of IGF-1 levels of these F2 mice detected fou...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2010.00612.x

    authors: Leduc MS,Hageman RS,Meng Q,Verdugo RA,Tsaih SW,Churchill GA,Paigen B,Yuan R

    更新日期:2010-10-01 00:00:00

  • Telomere-independent cellular senescence in human fetal cardiomyocytes.

    abstract::Fetal cardiomyocytes have been proposed as a potential source of cell-based therapy for heart failure. This study examined cellular senescence in cultured human fetal ventricular cardiomyocytes (HFCs). HFCs were isolated and identified by immunocytochemistry and RT-PCR. Cells were found to senesce after 20-25 populati...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9728.2004.00137.x

    authors: Ball AJ,Levine F

    更新日期:2005-02-01 00:00:00

  • Conserved cysteine residues in the mammalian lamin A tail are essential for cellular responses to ROS generation.

    abstract::Pre-lamin A and progerin have been implicated in normal aging, and the pathogenesis of age-related degenerative diseases is termed 'laminopathies'. Here, we show that mature lamin A has an essential role in cellular fitness and that oxidative damage to lamin A is involved in cellular senescence. Primary human dermal f...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2011.00750.x

    authors: Pekovic V,Gibbs-Seymour I,Markiewicz E,Alzoghaibi F,Benham AM,Edwards R,Wenhert M,von Zglinicki T,Hutchison CJ

    更新日期:2011-12-01 00:00:00

  • The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging.

    abstract::Sarcopenia, the loss of skeletal muscle mass and function during aging, is a major contributor to disability and frailty in the elderly. Previous studies found a protective effect of reduced histone deacetylase activity in models of neurogenic muscle atrophy. Because loss of muscle mass during aging is associated with...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12387

    authors: Walsh ME,Bhattacharya A,Sataranatarajan K,Qaisar R,Sloane L,Rahman MM,Kinter M,Van Remmen H

    更新日期:2015-12-01 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

  • Sustained high levels of neuregulin-1 in the longest-lived rodents; a key determinant of rodent longevity.

    abstract::Naked mole-rats (Heterocephalus glaber), the longest-lived rodents, live 7-10 times longer than similarly sized mice and exhibit normal activities for approximately 75% of their lives. Little is known about the mechanisms that allow them to delay the aging process and live so long. Neuregulin-1 (NRG-1) signaling is cr...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2011.00772.x

    authors: Edrey YH,Casper D,Huchon D,Mele J,Gelfond JA,Kristan DM,Nevo E,Buffenstein R

    更新日期:2012-04-01 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

  • Reversal of aging-associated hippocampal synaptic plasticity deficits by reductants via regulation of thiol redox and NMDA receptor function.

    abstract::Deficits in learning and memory accompanied by age-related neurodegenerative diseases are closely related to the impairment of synaptic plasticity. In this study, we investigated the role of thiol redox status in the modulation of the N-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) in CA1 ...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2010.00595.x

    authors: Yang YJ,Wu PF,Long LH,Yu DF,Wu WN,Hu ZL,Fu H,Xie N,Jin Y,Ni L,Wang JZ,Wang F,Chen JG

    更新日期:2010-10-01 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

  • The G/C915 polymorphism of transforming growth factor beta1 is associated with human longevity: a study in Italian centenarians.

    abstract::Sequence variations in a variety of pro- or anti-inflammatory cytokine genes have been found to influence successful aging and longevity. Because of the role played by the transforming growth factor beta1 (TGF-beta1) cytokine in inflammation and regulation of immune responses, the variability of the TGF-beta1 gene may...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9728.2004.00129.x

    authors: Carrieri G,Marzi E,Olivieri F,Marchegiani F,Cavallone L,Cardelli M,Giovagnetti S,Stecconi R,Molendini C,Trapassi C,De Benedictis G,Kletsas D,Franceschi C

    更新日期:2004-12-01 00:00:00

  • Caenorhabditis elegans orthologs of human genes differentially expressed with age are enriched for determinants of longevity.

    abstract::We report a systematic RNAi longevity screen of 82 Caenorhabditis elegans genes selected based on orthology to human genes differentially expressed with age. We find substantial enrichment in genes for which knockdown increased lifespan. This enrichment is markedly higher than published genomewide longevity screens in...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12595

    authors: Sutphin GL,Backer G,Sheehan S,Bean S,Corban C,Liu T,Peters MJ,van Meurs JBJ,Murabito JM,Johnson AD,Korstanje R,Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Gene Expression Working Group.

    更新日期:2017-08-01 00:00:00

  • Endocrine targets for pharmacological intervention in aging in Caenorhabditis elegans.

    abstract::Studies in the nematode Caenorhabditis elegans have been instrumental in defining genetic pathways that are involved in modulating lifespan. Multiple processes such as endocrine signaling, nutritional sensing and mitochondrial function play a role in determining lifespan in the worm and these mechanisms appear to be c...

    journal_title:Aging cell

    pub_type: 杂志文章,评审

    doi:10.1111/j.1474-9726.2006.00186.x

    authors: Gill MS

    更新日期:2006-02-01 00:00:00

  • Sex differences in survival and mitochondrial bioenergetics during aging in Drosophila.

    abstract::The goal of this study is to test the role of mitochondria and of mitochondrial metabolism in determining the processes that influence aging of female and male Drosophila. We observe that Drosophila simulans females tended to have shorter lifespan, higher levels of hydrogen peroxide production and significantly lower ...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2007.00331.x

    authors: Ballard JW,Melvin RG,Miller JT,Katewa SD

    更新日期:2007-10-01 00:00:00

  • Ultrastructure of the liver microcirculation influences hepatic and systemic insulin activity and provides a mechanism for age-related insulin resistance.

    abstract::While age-related insulin resistance and hyperinsulinemia are usually considered to be secondary to changes in muscle, the liver also plays a key role in whole-body insulin handling and its role in age-related changes in insulin homeostasis is largely unknown. Here, we show that patent pores called 'fenestrations' are...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12481

    authors: Mohamad M,Mitchell SJ,Wu LE,White MY,Cordwell SJ,Mach J,Solon-Biet SM,Boyer D,Nines D,Das A,Catherine Li SY,Warren A,Hilmer SN,Fraser R,Sinclair DA,Simpson SJ,de Cabo R,Le Couteur DG,Cogger VC

    更新日期:2016-08-01 00:00:00

  • PKR knockout in the 5xFAD model of Alzheimer's disease reveals beneficial effects on spatial memory and brain lesions.

    abstract::Brain lesions in Alzheimer's disease (AD) include amyloid plaques made of Aβ peptides and neurofibrillary tangles composed of hyperphosphorylated tau protein with synaptic and neuronal loss and neuroinflammation. Aβ oligomers can trigger tau phosphorylation and neuronal alterations through activation of neuronal kinas...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12887

    authors: Tible M,Mouton Liger F,Schmitt J,Giralt A,Farid K,Thomasseau S,Gourmaud S,Paquet C,Rondi Reig L,Meurs E,Girault JA,Hugon J

    更新日期:2019-06-01 00:00:00

  • Endoplasmic reticulum stress occurs downstream of GluN2B subunit of N-methyl-d-aspartate receptor in mature hippocampal cultures treated with amyloid-β oligomers.

    abstract::Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting both the hippocampus and the cerebral cortex. Reduced synaptic density that occurs early in the disease process seems to be partially due to the overactivation of N-methyl-d-aspartate receptors (NMDARs) leading to excitotoxicity. Recently, ...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2012.00848.x

    authors: Costa RO,Lacor PN,Ferreira IL,Resende R,Auberson YP,Klein WL,Oliveira CR,Rego AC,Pereira CM

    更新日期:2012-10-01 00:00:00

  • Flagellin-dependent TLR5/caveolin-1 as a promising immune activator in immunosenescence.

    abstract::The age-associated decline of immune responses causes high susceptibility to infections and reduced vaccine efficacy in the elderly. However, the mechanisms underlying age-related deficits are unclear. Here, we found that the expression and signaling of flagellin (FlaB)-dependent Toll-like receptor 5 (TLR5), unlike th...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12383

    authors: Lim JS,Nguyen KC,Nguyen CT,Jang IS,Han JM,Fabian C,Lee SE,Rhee JH,Cho KA

    更新日期:2015-10-01 00:00:00

  • Selective induction of calcineurin activity and signaling by oligomeric amyloid beta.

    abstract::Alzheimer's disease (AD) is a terminal age-associated dementia characterized by early synaptic dysfunction and late neurodegeneration. Although the presence of plaques of fibrillar aggregates of the amyloid beta peptide (Abeta) is a signature of AD, evidence suggests that the preplaque small oligomeric Abeta promotes ...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2008.00434.x

    authors: Reese LC,Zhang W,Dineley KT,Kayed R,Taglialatela G

    更新日期:2008-12-01 00:00:00

  • Treatment with the mitochondrial-targeted antioxidant peptide SS-31 rescues neurovascular coupling responses and cerebrovascular endothelial function and improves cognition in aged mice.

    abstract::Moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling has an essential role in maintenance of healthy cognitive function. In advanced age, increased oxidative stress and cerebromicrovascular endothelial dysfunction impair neurovascular coupling, likely contributing to age-related decline ...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12731

    authors: Tarantini S,Valcarcel-Ares NM,Yabluchanskiy A,Fulop GA,Hertelendy P,Gautam T,Farkas E,Perz A,Rabinovitch PS,Sonntag WE,Csiszar A,Ungvari Z

    更新日期:2018-04-01 00:00:00

  • Deletion of ghrelin prevents aging-associated obesity and muscle dysfunction without affecting longevity.

    abstract::During aging, decreases in energy expenditure and locomotor activity lead to body weight and fat gain. Aging is also associated with decreases in muscle strength and endurance leading to functional decline. Here, we show that lifelong deletion of ghrelin prevents development of obesity associated with aging by modulat...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12618

    authors: Guillory B,Chen JA,Patel S,Luo J,Splenser A,Mody A,Ding M,Baghaie S,Anderson B,Iankova B,Halder T,Hernandez Y,Garcia JM

    更新日期:2017-08-01 00:00:00

  • Genomewide mechanisms of chronological longevity by dietary restriction in budding yeast.

    abstract::Dietary restriction is arguably the most promising nonpharmacological intervention to extend human life and health span. Yet, only few genetic regulators mediating the cellular response to dietary restriction are known, and the question remains which other regulatory factors are involved. Here, we measured at the geno...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12749

    authors: Campos SE,Avelar-Rivas JA,Garay E,Juárez-Reyes A,DeLuna A

    更新日期:2018-06-01 00:00:00

  • Epidermal stem cells are resistant to cellular aging.

    abstract::The epidermis of the skin, acting as the primary physical barrier between self and environment, is a dynamic tissue whose maintenance is critical to the survival of an organism. Like most other tissues and organs, the epidermis is maintained and repaired by a population of resident somatic stem cells. The epidermal st...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2007.00318.x

    authors: Stern MM,Bickenbach JR

    更新日期:2007-08-01 00:00:00

  • IGF-I regulates the age-dependent signaling peptide humanin.

    abstract::Aging is influenced by endocrine pathways including the growth hormone/insulin-like growth factor-1 (GH/IGF) axis. Mitochondrial function has also been linked to the aging process, but the relevant mitochondrial signals mediating the effects of mitochondria are poorly understood. Humanin is a novel signaling peptide t...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12243

    authors: Lee C,Wan J,Miyazaki B,Fang Y,Guevara-Aguirre J,Yen K,Longo V,Bartke A,Cohen P

    更新日期:2014-10-01 00:00:00

  • JNK modifies neuronal metabolism to promote proteostasis and longevity.

    abstract::Aging is associated with a progressive loss of tissue and metabolic homeostasis. This loss can be delayed by single-gene perturbations, increasing lifespan. How such perturbations affect metabolic and proteostatic networks to extend lifespan remains unclear. Here, we address this question by comprehensively characteri...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12849

    authors: Wang L,Davis SS,Borch Jensen M,Rodriguez-Fernandez IA,Apaydin C,Juhasz G,Gibson BW,Schilling B,Ramanathan A,Ghaemmaghami S,Jasper H

    更新日期:2019-06-01 00:00:00

  • Loss of HDAC3 contributes to meiotic defects in aged oocytes.

    abstract::Maternal age-related decline in oocyte quality is associated with meiotic defects, but the underlying mechanisms remain to be explored. Histone deacetylase 3 (HDAC3) has been shown to govern multiple cellular events via deacetylating diverse substrates. We previously found that HDAC3 could promote meiotic apparatus as...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.13036

    authors: He Y,Li X,Gao M,Liu H,Gu L

    更新日期:2019-12-01 00:00:00