Surface L-type Ca2+ channel expression levels are increased in aged hippocampus.

Abstract:

:Age-related increase in L-type Ca(2+) channel (LTCC) expression in hippocampal pyramidal neurons has been hypothesized to underlie the increased Ca(2+) influx and subsequent reduced intrinsic neuronal excitability of these neurons that lead to age-related cognitive deficits. Here, using specific antibodies against Cav 1.2 and Cav 1.3 subunits of LTCCs, we systematically re-examined the expression of these proteins in the hippocampus from young (3 to 4 month old) and aged (30 to 32 month old) F344xBN rats. Western blot analysis of the total expression levels revealed significant reductions in both Cav 1.2 and Cav 1.3 subunits from all three major hippocampal regions of aged rats. Despite the decreases in total expression levels, surface biotinylation experiments revealed significantly higher proportion of expression on the plasma membrane of Cav 1.2 in the CA1 and CA3 regions and of Cav 1.3 in the CA3 region from aged rats. Furthermore, the surface biotinylation results were supported by immunohistochemical analysis that revealed significant increases in Cav 1.2 immunoreactivity in the CA1 and CA3 regions of aged hippocampal pyramidal neurons. In addition, we found a significant increase in the level of phosphorylated Cav 1.2 on the plasma membrane in the dentate gyrus of aged rats. Taken together, our present findings strongly suggest that age-related cognitive deficits cannot be attributed to a global change in L-type channel expression nor to the level of phosphorylation of Cav 1.2 on the plasma membrane of hippocampal neurons. Rather, increased expression and density of LTCCs on the plasma membrane may underlie the age-related increase in L-type Ca(2+) channel activity in CA1 pyramidal neurons.

journal_name

Aging Cell

journal_title

Aging cell

authors

Núñez-Santana FL,Oh MM,Antion MD,Lee A,Hell JW,Disterhoft JF

doi

10.1111/acel.12157

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

111-20

issue

1

eissn

1474-9718

issn

1474-9726

journal_volume

13

pub_type

杂志文章
  • FOXO protects against age-progressive axonal degeneration.

    abstract::Neurodegeneration resulting in cognitive and motor impairment is an inevitable consequence of aging. Little is known about the genetic regulation of this process despite its overriding importance in normal aging. Here, we identify the Forkhead Box O (FOXO) transcription factor 1, 3, and 4 isoforms as a guardian of neu...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12701

    authors: Hwang I,Oh H,Santo E,Kim DY,Chen JW,Bronson RT,Locasale JW,Na Y,Lee J,Reed S,Toth M,Yu WH,Muller FL,Paik J

    更新日期:2018-02-01 00:00:00

  • Low plasma lysophosphatidylcholines are associated with impaired mitochondrial oxidative capacity in adults in the Baltimore Longitudinal Study of Aging.

    abstract::The decrease in skeletal muscle mitochondrial oxidative capacity with age adversely affects muscle strength and physical performance. Factors that are associated with this decrease have not been well characterized. Low plasma lysophosphatidylcholines (LPC), a major class of systemic bioactive lipids, are predictive of...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12915

    authors: Semba RD,Zhang P,Adelnia F,Sun K,Gonzalez-Freire M,Salem N Jr,Brennan N,Spencer RG,Fishbein K,Khadeer M,Shardell M,Moaddel R,Ferrucci L

    更新日期:2019-04-01 00:00:00

  • Sex-specific effects of protein and carbohydrate intake on reproduction but not lifespan in Drosophila melanogaster.

    abstract::Modest dietary restriction extends lifespan (LS) in a diverse range of taxa and typically has a larger effect in females than males. Traditionally, this has been attributed to a stronger trade-off between LS and reproduction in females than in males that is mediated by the intake of calories. Recent studies, however, ...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12333

    authors: Jensen K,McClure C,Priest NK,Hunt J

    更新日期:2015-08-01 00:00:00

  • Sarcopenia is not due to lack of regenerative drive in senescent skeletal muscle.

    abstract::Sarcopenia, loss of skeletal muscle mass, is a hallmark of aging commonly attributed to a decreased capacity to maintain muscle tissue in senescence, yet the mechanism behind the muscle wasting remains unresolved. To address these issues we have explored a rodent model of sarcopenia and age-related sensorimotor impair...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9728.2005.00145.x

    authors: Edström E,Ulfhake B

    更新日期:2005-04-01 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

  • Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice.

    abstract::We tested the hypothesis that supplementation of nicotinamide mononucleotide (NMN), a key NAD(+) intermediate, increases arterial SIRT1 activity and reverses age-associated arterial dysfunction and oxidative stress. Old control mice (OC) had impaired carotid artery endothelium-dependent dilation (EDD) (60 ± 5% vs. 84 ...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12461

    authors: de Picciotto NE,Gano LB,Johnson LC,Martens CR,Sindler AL,Mills KF,Imai S,Seals DR

    更新日期:2016-06-01 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

  • 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

  • The general control nonderepressible-2 kinase mediates stress response and longevity induced by target of rapamycin inactivation in Caenorhabditis elegans.

    abstract::The general control nonderepressible 2 (GCN2) kinase is a nutrient-sensing pathway that responds to amino acids deficiency and induces a genetic program to effectively maintain cellular homeostasis. Here we established the conserved role of Caenorhabditis elegans GCN-2 under amino acid limitation as a translation init...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12101

    authors: Rousakis A,Vlassis A,Vlanti A,Patera S,Thireos G,Syntichaki P

    更新日期:2013-10-01 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

  • Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice.

    abstract::Neurogenesis, which may contribute to the ability of the adult brain to function normally and adapt to disease, nevertheless declines with advancing age. Adult neurogenesis can be enhanced by administration of growth factors, but whether the aged brain remains responsive to these factors is unknown. We compared the ef...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1046/j.1474-9728.2003.00046.x

    authors: Jin K,Sun Y,Xie L,Batteur S,Mao XO,Smelick C,Logvinova A,Greenberg DA

    更新日期:2003-06-01 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

  • Lifespan extension in Caenorhabditis elegans by complete removal of food.

    abstract::A partial reduction in food intake has been found to increase lifespan in many different organisms. We report here a new dietary restriction regimen in the nematode Caenorhabditis elegans, based on the standard agar plate lifespan assay, in which adult worms are maintained in the absence of a bacterial food source. Th...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2006.00238.x

    authors: Kaeberlein TL,Smith ED,Tsuchiya M,Welton KL,Thomas JH,Fields S,Kennedy BK,Kaeberlein M

    更新日期:2006-12-01 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

  • Calcium buffering systems and calcium signaling in aged rat basal forebrain neurons.

    abstract::Disturbances of neuronal Ca2+ homeostasis are considered to be important determinants of age-related cognitive impairment. Cholinergic neurons of the basal forebrain (BF) are principal targets of decline associated with aging and dementia. During the last several years, we have attempted to link these concepts in a ra...

    journal_title:Aging cell

    pub_type: 杂志文章,评审

    doi:10.1111/j.1474-9726.2007.00293.x

    authors: Murchison D,Griffith WH

    更新日期:2007-06-01 00:00:00

  • How age and infection history shape the antigen-specific CD8+ T-cell repertoire: Implications for vaccination strategies in older adults.

    abstract::Older adults often show signs of impaired CD8+ T-cell immunity, reflected by weaker responses against new infections and vaccinations, and decreased protection against reinfection. This immune impairment is in part thought to be the consequence of a decrease in both T-cell numbers and repertoire diversity. If this is ...

    journal_title:Aging cell

    pub_type: 杂志文章,评审

    doi:10.1111/acel.13262

    authors: Lanfermeijer J,Borghans JAM,van Baarle D

    更新日期:2020-11-01 00:00:00

  • Identification of stable senescence-associated reference genes.

    abstract::Cellular senescence is a state of permanent cell cycle arrest activated in response to damaging stimuli. Many hallmarks associated with senescent cells are measured by quantitative real-time PCR (qPCR). As the selection of stable reference genes for interpretation of qPCR data is often overlooked, we performed a syste...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12911

    authors: Hernandez-Segura A,Rubingh R,Demaria M

    更新日期:2019-04-01 00:00:00

  • Gene expression-based drug repurposing to target aging.

    abstract::Aging is the largest risk factor for a variety of noncommunicable diseases. Model organism studies have shown that genetic and chemical perturbations can extend both lifespan and healthspan. Aging is a complex process, with parallel and interacting mechanisms contributing to its aetiology, posing a challenge for the d...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12819

    authors: Dönertaş HM,Fuentealba Valenzuela M,Partridge L,Thornton JM

    更新日期:2018-10-01 00:00:00

  • Ventriculomegaly associated with ependymal gliosis and declines in barrier integrity in the aging human and mouse brain.

    abstract::Age-associated ventriculomegaly is typically attributed to neurodegeneration; however, additional factors might initiate or contribute to progressive ventricular expansion. By directly linking postmortem human MRI sequences with histological features of periventricular tissue, we show that substantial lateral ventricl...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12184

    authors: Shook BA,Lennington JB,Acabchuk RL,Halling M,Sun Y,Peters J,Wu Q,Mahajan A,Fellows DW,Conover JC

    更新日期:2014-04-01 00:00:00

  • The PI3K-Akt pathway inhibits senescence and promotes self-renewal of human skin-derived precursors in vitro.

    abstract::Skin-derived precursors (SKPs) are embryonic neural crest- or somite-derived multipotent progenitor cells with properties of dermal stem cells. Although a large number of studies deal with their differentiation ability and potential applications in tissue damage repair, only a few studies have concentrated on the regu...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2011.00704.x

    authors: Liu S,Liu S,Wang X,Zhou J,Cao Y,Wang F,Duan E

    更新日期:2011-08-01 00:00:00

  • Mitochondrial mass governs the extent of human T cell senescence.

    abstract::The susceptibility of human CD4+ and CD8+ T cells to senesce differs, with CD8+ T cells acquiring an immunosenescent phenotype faster than the CD4+ T cell compartment. We show here that it is the inherent difference in mitochondrial content that drives this phenotype, with senescent human CD4+ T cells displaying a hig...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.13067

    authors: Callender LA,Carroll EC,Bober EA,Akbar AN,Solito E,Henson SM

    更新日期:2020-02-01 00:00:00

  • Testing the 'free radical theory of aging' hypothesis: physiological differences in long-lived and short-lived colubrid snakes.

    abstract::We test the 'free radical theory of aging' using six species of colubrid snakes (numerous, widely distributed, non-venomous snakes of the family Colubridae) that exhibit long (> 15 years) or short (< 10 years) lifespans. Because the 'rate of living theory' predicts metabolic rates to be correlated with rates of aging ...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2007.00287.x

    authors: Robert KA,Brunet-Rossinni A,Bronikowski AM

    更新日期:2007-06-01 00:00:00

  • The GATA transcription factor/MTA-1 homolog egr-1 promotes longevity and stress resistance in Caenorhabditis elegans.

    abstract::Aging is associated with a large number of both phenotypic and molecular changes, but for most of these, it is not known whether these changes are detrimental, neutral, or protective. We have identified a conserved Caenorhabditis elegans GATA transcription factor/MTA-1 homolog egr-1 (lin-40) that extends lifespan and ...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12179

    authors: Zimmerman SM,Kim SK

    更新日期:2014-04-01 00:00:00

  • Telomerase reverse transcriptase haploinsufficiency and telomere length in individuals with 5p- syndrome.

    abstract::Telomerase, which maintains the ends of chromosomes, consists of two core components, the telomerase reverse transcriptase (TERT) and the telomerase RNA (TERC). Haploinsufficiency for TERC or TERT leads to progressive telomere shortening and autosomal dominant dyskeratosis congenita (DC). The clinical manifestations o...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2007.00324.x

    authors: Du HY,Idol R,Robledo S,Ivanovich J,An P,Londono-Vallejo A,Wilson DB,Mason PJ,Bessler M

    更新日期:2007-10-01 00:00:00

  • A dual role for integrin-linked kinase and β1-integrin in modulating cardiac aging.

    abstract::Cardiac performance decreases with age, which is a major risk factor for cardiovascular disease and mortality in the aging human population, but the molecular mechanisms underlying cardiac aging are still poorly understood. Investigating the role of integrin-linked kinase (ilk) and β1-integrin (myospheroid, mys) in Dr...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12193

    authors: Nishimura M,Kumsta C,Kaushik G,Diop SB,Ding Y,Bisharat-Kernizan J,Catan H,Cammarato A,Ross RS,Engler AJ,Bodmer R,Hansen M,Ocorr K

    更新日期:2014-06-01 00:00:00

  • Sterol regulatory element-binding protein-1c orchestrates metabolic remodeling of white adipose tissue by caloric restriction.

    abstract::Caloric restriction (CR) can delay onset of several age-related pathophysiologies and extend lifespan in various species, including rodents. CR also induces metabolic remodeling involved in activation of lipid metabolism, enhancement of mitochondrial biogenesis, and reduction of oxidative stress in white adipose tissu...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12576

    authors: Fujii N,Narita T,Okita N,Kobayashi M,Furuta Y,Chujo Y,Sakai M,Yamada A,Takeda K,Konishi T,Sudo Y,Shimokawa I,Higami Y

    更新日期:2017-06-01 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

  • The acceleration of reproductive aging in Nrg1flox/flox ;Cyp19-Cre female mice.

    abstract::Irregular menstrual cycles, reduced responses to exogenous hormonal treatments, and altered endocrine profiles (high FSH/high LH/low AMH) are observed in women with increasing age before menopause. In this study, because the granulosa cell-specific Nrg1 knockout mice (gcNrg1KO) presented ovarian and endocrine phenotyp...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/acel.12662

    authors: Umehara T,Kawai T,Kawashima I,Tanaka K,Okuda S,Kitasaka H,Richards JS,Shimada M

    更新日期:2017-12-01 00:00:00

  • A neuroprotective role for the DNA damage checkpoint in tauopathy.

    abstract::ATM and p53, effectors of the DNA damage checkpoint, are generally considered pro-apoptotic in neurons. We show that DNA damage and checkpoint activation occurs in postmitotic neurons in animal models of tauopathy, neurodegenerative disorders that include Alzheimer's disease. Surprisingly, checkpoint attenuation poten...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2011.00778.x

    authors: Khurana V,Merlo P,DuBoff B,Fulga TA,Sharp KA,Campbell SD,Götz J,Feany MB

    更新日期:2012-04-01 00:00:00

  • Ambient temperature influences aging in an annual fish (Nothobranchius rachovii).

    abstract::Extending lifespan by lowering ambient temperature in the habitat has been shown in a variety of organisms. Its mechanism, however, remains elusive. In this study, we examined the survivorship and the aging process of the annual fish (Nothobranchius rachovii) reared under high (30 degrees C), moderate (25 degrees C) a...

    journal_title:Aging cell

    pub_type: 杂志文章

    doi:10.1111/j.1474-9726.2009.00525.x

    authors: Hsu CY,Chiu YC

    更新日期:2009-12-01 00:00:00