Modeling of lamin A/C mutation premature cardiac aging using patient‐specific induced pluripotent stem cells.

Abstract:

AIMS:We identified an autosomal dominant non‐sense mutation (R225X) in exon 4 of the lamin A/C (LMNA) gene in a Chinese family spanning 3 generations with familial dilated cardiomyopathy (DCM). In present study, we aim to generate induced pluripotent stem cells derived cardiomyocytes (iPSC‐CMs) from an affected patient with R225X and another patient bearing LMNA frame‐shift mutation for drug screening. METHODS AND RESULTS:Higher prevalence of nuclear bleb formation and micronucleation was present in LMNA(R225X/WT) and LMNA(Framshift/WT) iPSC‐CMs. Under field electrical stimulation, percentage of LMNA‐mutated iPSC‐CMs exhibiting nuclear senescence and cellular apoptosis markedly increased. shRNA knockdown of LMNA replicated those phenotypes of the mutated LMNA field electrical stress. Pharmacological blockade of ERK1/2 pathway with MEK1/2 inhibitors, U0126 and selumetinib (AZD6244) significantly attenuated the pro‐apoptotic effects of field electric stimulation on the mutated LMNA iPSC‐CMs. CONCLUSION:LMNA‐related DCM was modeled in‐vitro using patient‐specific iPSC‐CMs. Our results demonstrated that haploinsufficiency due to R225X LMNA non‐sense mutation was associated with accelerated nuclear senescence and apoptosis of iPSC‐ CMs under electrical stimulation, which can be significantly attenuated by therapeutic blockade of stress‐related ERK1/2 pathway.

journal_name

Aging (Albany NY)

journal_title

Aging

authors

Siu CW,Lee YK,Ho JC,Lai WH,Chan YC,Ng KM,Wong LY,Au KW,Lau YM,Zhang J,Lay KW,Colman A,Tse HF

doi

10.18632/aging.100503

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

803-822

issue

11

issn

1945-4589

journal_volume

4

pub_type

杂志文章

相关文献

Aging-US文献大全
  • Caloric restriction effects on liver mTOR signaling are time-of-day dependent.

    abstract::The regulation of mechanistic target of rapamycin (mTOR) signaling contributes to the metabolic effects of a calorie restriction (CR) diet. We assayed the effect of CR on the activity of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) in the liver of mice at six different times across the day. CR effects on mTORC1...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101498

    authors: Tulsian R,Velingkaar N,Kondratov R

    更新日期:2018-07-16 00:00:00

  • Dopamine suppresses octopamine signaling in C. elegans: possible involvement of dopamine in the regulation of lifespan.

    abstract::Amine neurotransmitters, such as dopamine, serotonin, and noradrenaline, play important roles in the modulation of behaviors and metabolism of animals. InC. elegans, it has been shown that serotonin and octopamine, an invertebrate equivalent of noradrenaline, also regulate lifespan through a mechanism related to food ...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100097

    authors: Suo S,Culotti JG,Van Tol HH

    更新日期:2009-10-21 00:00:00

  • Biomarkers of aging and lung function in the normative aging study.

    abstract::Elderly individuals who are never smokers but have the same height and chronological age can have substantial differences in lung function. The underlying biological mechanisms are unclear. To evaluate the associations of different biomarkers of aging (BoA) and lung function, we performed a repeated-measures analysis ...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103363

    authors: Wang C,Just A,Heiss J,Coull BA,Hou L,Zheng Y,Sparrow D,Vokonas PS,Baccarelli A,Schwartz J

    更新日期:2020-06-19 00:00:00

  • Role of FUT8 expression in clinicopathology and patient survival for various malignant tumor types: A systematic review and meta-analysis.

    abstract::Dysregulation of α(1,6)-fucosyltransferase (FUT8) plays significant roles in development of a variety of malignant tumor types. We collected as many relevant articles and microarray datasets as possible to assess the prognostic value of FUT8 expression in malignant tumors. For this purpose, we systematically searched ...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.202239

    authors: Ma M,Han G,Wang Y,Zhao Z,Guan F,Li X

    更新日期:2020-12-11 00:00:00

  • Longitudinal plasma metabolomics of aging and sex.

    abstract::Understanding how metabolites are longitudinally influenced by age and sex could facilitate the identification of metabolomic profiles and trajectories that indicate disease risk. We investigated the metabolomics of age and sex using longitudinal plasma samples from the Wisconsin Registry for Alzheimer's Prevention (W...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101837

    authors: Darst BF,Koscik RL,Hogan KJ,Johnson SC,Engelman CD

    更新日期:2019-02-24 00:00:00

  • Increased intrinsic default-mode network activity as a compensatory mechanism in aMCI: a resting-state functional connectivity MRI study.

    abstract::Numerous studies have investigated the differences in the mean functional connectivity (FC) strength between amnestic mild cognitive impairment (aMCI) patients and normal subjects using resting-state functional magnetic resonance imaging. However, whether the mean FC is increased, decreased or unchanged in aMCI patien...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.102986

    authors: Liang J,Li Y,Liu H,Zhang S,Wang M,Chu Y,Ye J,Xi Q,Zhao X

    更新日期:2020-04-01 00:00:00

  • Association of VAMP5 and MCC genetic polymorphisms with increased risk of Hirschsprung disease susceptibility in Southern Chinese children.

    abstract::Hirschsprung disease (HSCR) is a genetic disorder characterized by the absence of neural crest cells in parts of the intestine. This study aims to investigate the association of vesicle-associated membrane protein 5 (VAMP5) and mutated in colorectal cancer (MCC) genetic polymorphisms and their correlated risks with HS...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101423

    authors: Zhao J,Xie X,Yao Y,He Q,Zhang R,Xia H,Zhang Y

    更新日期:2018-04-25 00:00:00

  • Age-associated chromatin relaxation is enhanced in Huntington's disease mice.

    abstract::Expansion of polyglutamine stretch in the huntingtin (HTT) protein is a major cause of Huntington's disease (HD). The polyglutamine part in HTT interacts with various proteins implicated in epigenetic regulation of genes, suggesting that mutant HTT may disturb the integrity of the epigenetic system. Here, we used a PC...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101193

    authors: Park M,Min B,Jeon K,Cho S,Park JS,Kim J,Jeon J,Song J,Kim S,Jeong S,Seo H,Kang YK

    更新日期:2017-03-12 00:00:00

  • Analysis of the machinery and intermediates of the 5hmC-mediated DNA demethylation pathway in aging on samples from the MARK-AGE Study.

    abstract::Gradual changes in the DNA methylation landscape occur throughout aging virtually in all human tissues. A widespread reduction of 5-methylcytosine (5mC), associated with highly reproducible site-specific hypermethylation, characterizes the genome in aging. Therefore, an equilibrium seems to exist between general and d...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101022

    authors: Valentini E,Zampieri M,Malavolta M,Bacalini MG,Calabrese R,Guastafierro T,Reale A,Franceschi C,Hervonen A,Koller B,Bernhardt J,Slagboom PE,Toussaint O,Sikora E,Gonos ES,Breusing N,Grune T,Jansen E,Dollé ME,Moreno-Vi

    更新日期:2016-08-29 00:00:00

  • Long noncoding RNA LINC00461 induced osteoarthritis progression by inhibiting miR-30a-5p.

    abstract::Mounting studies have shown that long noncoding RNAs (lncRNAs) play important roles in the development and occurrence of several human diseases. However, the role of LINC00461 in osteoarthritis (OA) remains obscure. A CCK-8 assay was performed to detect cell viability, and qRT-PCR analysis was used to measure mRNA exp...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.102839

    authors: Zhang Y,Ma L,Wang C,Wang L,Guo Y,Wang G

    更新日期:2020-03-10 00:00:00

  • Psychological stress exposure to aged mice causes abnormal feeding patterns with changes in the bout number.

    abstract::Stress responses are affected by aging. However, studies on stress-related changes in feeding patterns with aging subject are minimal. We investigated feeding patterns induced by two psychological stress models, revealing characteristics of stress-induced feeding patterns as "meal" and "bout" (defined as the minimum f...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101320

    authors: Yamada C,Mogami S,Hattori T

    更新日期:2017-11-09 00:00:00

  • APOE ε4 allele accelerates age-related multi-cognitive decline and white matter damage in non-demented elderly.

    abstract::Advanced age and apolipoprotein E (APOE) ε4 allele are both associated with increased risk of the Alzheimer's disease (AD). However, the extent of the joint contribution of APOE ε4 allele and age on the brain white matter integrity, cognition and their relationship are unclear. We assessed the age-related variation di...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103367

    authors: Sun J,Zhu Z,Chen K,Wei D,Li X,Li H,Zhang J,Chen X,Chen Y,Zhang Z

    更新日期:2020-06-22 00:00:00

  • Characterization of variations in IL23A and IL23R genes: possible roles in multiple sclerosis and other neuroinflammatory demyelinating diseases.

    abstract::Multiple sclerosis is among the most serious inflammatory demyelinating diseases (IDD). Interleukin-23A (IL23A) regulates and coordinates the activities of immune cells by interacting with its receptor IL23R and plays key roles in the pathogenesis of immune inflammatory diseases. IDD, deemed to be a kind of autoimmune...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.101058

    authors: Li FF,Zhu XD,Yan P,Jin MH,Yue H,Zhang Q,Fu J,Liu SL

    更新日期:2016-11-26 00:00:00

  • Multiple dietary supplements do not affect metabolic and cardio-vascular health.

    abstract::Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. ...

    journal_title:Aging

    pub_type: 杂志文章,随机对照试验

    doi:10.18632/aging.100597

    authors: Soare A,Weiss EP,Holloszy JO,Fontana L

    更新日期:2014-02-01 00:00:00

  • Telomere-dependent and telomere-independent origins of endogenous DNA damage in tumor cells.

    abstract::Human tumors and cultured cells contain elevated levels of endogenous DNA damage resulting from telomere dysfunction, replication and transcription errors, reactive oxygen species, and genome instability. However, the contribution of telomere-associated versus telomere-independent endogenous DNA lesions to this damage...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100019

    authors: Nakamura AJ,Redon CE,Bonner WM,Sedelnikova OA

    更新日期:2009-02-04 00:00:00

  • Cross-platform genomic identification and clinical validation of breast cancer diagnostic biomarkers.

    abstract:INTRODUCTION:Circulating non-coding RNA is an ideal source to discover novel biomarkers for non-invasive screening. However, studies for the discovery of universal miRNAs in serum and exosomes for breast cancer early diagnosis are limited. METHODS:Based on bioinformatic analysis, in vitro and in vivo studies were perf...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.202388

    authors: Liu D,Li B,Shi X,Zhang J,Chen AM,Xu J,Wang W,Huang K,Gao J,Zheng Z,Liu D,Wang H,Shi W,Chen L,Xu J

    更新日期:2021-01-20 00:00:00

  • LINC00514 drives osteosarcoma progression through sponging microRNA-708 and consequently increases URGCP expression.

    abstract::Long intergenic nonprotein-coding RNA 00514 (LINC00514) is upregulated in papillary thyroid cancer and contributes to its aggressiveness. In this study, we thoroughly explored the expression profile, specific functions, and relevant molecular mechanism of LINC00514 in osteosarcoma (OS). Herein, LINC00514 was significa...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103043

    authors: Yu D,Xu X,Li S,Zhang K

    更新日期:2020-04-23 00:00:00

  • Elevated homocysteine as an independent risk for intracranial atherosclerotic stenosis.

    abstract::To investigate the association of homocysteine concentration with intracranial atherosclerotic stenosis (ICAS), we assessed 933 acute ischemic stroke patients (346 with ICAS, 587 without ICAS) and 798 non-stroke controls (175 with ICAS, 623 without ICAS) with magnetic resonance angiography (MRA). Homocysteine concentr...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.102019

    authors: Liu Y,Song JH,Hou XH,Ma YH,Shen XN,Xu W,Sun FR,Dong Q,Yu JT,Tan L,Chi S

    更新日期:2019-06-12 00:00:00

  • Survival of irradiated recipient mice after transplantation of bone marrow from young, old and "early aging" mice.

    abstract::Bone marrow transplantation is used to examine survival, hematopoietic stem cell function and pathology in recipients of young and old wild type bone marrow derived stem cells (BMDSCs) as well as cells from p53-based models of premature aging. There is no difference in the long term survival of recipients of 8 week-ol...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100867

    authors: Guest I,Ilic Z,Scrable H,Sell S

    更新日期:2015-12-01 00:00:00

  • Downregulation of circFASTKD1 ameliorates myocardial infarction by promoting angiogenesis.

    abstract::Circular RNAs (circRNAs), a novel class of endogenous long non-coding RNAs, have attracted considerable attention due to their closed continuous loop structure and potential clinical value. In this study, we investigated the function of circFASTKD1 in vascular endothelial cells. CircFASTKD1 bound directly to miR-106a ...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.202305

    authors: Gao WQ,Hu XM,Zhang Q,Yang L,Lv XZ,Chen S,Wu P,Duan DW,Lang YH,Ning M,Lai KG,Zhang ZY,Liang B,Bao JY,Wu HD,Li T

    更新日期:2020-12-19 00:00:00

  • Aging: Dial M for Mitochondria.

    abstract::A major goal of aging research is to identify interventions that prolong lifespan in distantly related organisms. In recent years, genetic studies in both nematodes and rodents have reported that moderate inactivation of genes important for mitochondrial electron transport chain (ETC) function can promote longevity. W...

    journal_title:Aging

    pub_type: 杂志文章,评审

    doi:10.18632/aging.100118

    authors: Hur JH,Cho J,Walker DW

    更新日期:2010-01-26 00:00:00

  • Stressor-responsive central nesfatin-1 activates corticotropin-releasing hormone, noradrenaline and serotonin neurons and evokes hypothalamic-pituitary-adrenal axis.

    abstract::A recently discovered satiety molecule, nesfatin-1, is localized in neurons of the hypothalamus and brain stem and colocalized with stress-related substances, corticotropin-releasing hormone (CRH), oxytocin, proopiomelanocortin, noradrenaline (NA) and 5-hydroxytryptamine (5-HT). Intracerebroventricular (icv) administr...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100207

    authors: Yoshida N,Maejima Y,Sedbazar U,Ando A,Kurita H,Damdindorj B,Takano E,Gantulga D,Iwasaki Y,Kurashina T,Onaka T,Dezaki K,Nakata M,Mori M,Yada T

    更新日期:2010-11-01 00:00:00

  • A newly defined risk signature, consisting of three m6A RNA methylation regulators, predicts the prognosis of ovarian cancer.

    abstract::N6-methyladenosine (m6A) RNA methylation, involved in cancer initiation and progression, is dynamically regulated by the m6A RNA methylation regulators. However, the expression of m6A RNA methylation regulators in ovarian cancer and their correlation with prognosis remain elusive. Here, we demonstrated that the 18 cen...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103811

    authors: Fan L,Lin Y,Lei H,Shu G,He L,Yan Z,Rihan H,Yin G

    更新日期:2020-09-20 00:00:00

  • Prevention of diet-induced hepatic steatosis and hepatic insulin resistance by second generation antisense oligonucleotides targeted to the longevity gene mIndy (Slc13a5).

    abstract::Reducing the expression of the Indy (I'm Not Dead Yet) gene in lower organisms extends life span by mechanisms resembling caloric restriction. Similarly, deletion of the mammalian homolog, mIndy (Slc13a5), encoding for a plasma membrane tricarboxylate transporter, protects from aging- and diet-induced adiposity and in...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100854

    authors: Pesta DH,Perry RJ,Guebre-Egziabher F,Zhang D,Jurczak M,Fischer-Rosinsky A,Daniels MA,Willmes DM,Bhanot S,Bornstein SR,Knauf F,Samuel VT,Shulman GI,Birkenfeld AL

    更新日期:2015-12-01 00:00:00

  • TIP-B1 promotes kidney clear cell carcinoma growth and metastasis via EGFR/AKT signaling.

    abstract::Kidney clear cell carcinoma (KIRC) is the most prevalent kidney malignancy. Accumulating evidence shows that high expression of TIP-B1 correlates with development of tumor progression. However, the detailed functions of TIP-B1 in the KIRC remain to be further elucidated. Here, we firstly found TIP-B1 expression was si...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.102298

    authors: Yin L,Gao S,Shi H,Wang K,Yang H,Peng B

    更新日期:2019-09-27 00:00:00

  • Inverse correlation between longevity and developmental rate among wild C. elegans strains.

    abstract::Genetic studies using model organisms have shown that many long-lived mutants display impaired fitness, such as reduced fecundity and delayed development. However, in several wild animals, the association between longevity and fitness does not seem to be inevitable. Thus, the relationship between longevity and fitness...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.100960

    authors: Lee Y,Hwang W,Jung J,Park S,Cabatbat JJ,Kim PJ,Lee SJ

    更新日期:2016-05-01 00:00:00

  • Circ_0006332 promotes growth and progression of bladder cancer by modulating MYBL2 expression via miR-143.

    abstract::In this study, we analyzed the role of circular RNAs in the growth and progression of bladder cancer. Direct Sanger sequencing and quantitative RT-PCR analysis showed that circ_0006332 was significantly upregulated in bladder cancer tissues. Sequencing analysis showed that circ_0006332 is generated from splicing of ex...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.102481

    authors: Li M,Liu Y,Liu J,Li W,Li N,Xue D,Zhang X,Wang P

    更新日期:2019-11-22 00:00:00

  • Histone proteomics reveals novel post-translational modifications in breast cancer.

    abstract::Histones and their variants are subjected to several post-translational modifications (PTMs). Histones PTMs play an important role in the regulation of gene expression and are critical for the development and progression of many types of cancer, including breast cancer. In this study, we used two-dimensional TAU/SDS e...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.102577

    authors: Perri AM,Agosti V,Olivo E,Concolino A,Angelis M,Tammè L,Fiumara CV,Cuda G,Scumaci D

    更新日期:2019-12-08 00:00:00

  • Sevoflurane postconditioning reduces myocardial ischemia reperfusion injury-induced necroptosis by up-regulation of OGT-mediated O-GlcNAcylated RIPK3.

    abstract::Inhalation anesthetics have been demonstrated to have protective effects against myocardial ischemia reperfusion injury (MIRI). O-linked GlcNAcylation (O-GlcNAc) modifications have been shown to protect against MIRI. This study aimed to investigate whether O-GlcNAcylation and necroptosis signaling were important for s...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.104146

    authors: Zhang J,Yu P,Hua F,Hu Y,Xiao F,Liu Q,Huang D,Deng F,Wei G,Deng W,Ma J,Zhu W,Zhang J,Yu S

    更新日期:2020-11-20 00:00:00

  • The clinicopathological characteristics and genetic alterations between younger and older gastric cancer patients with curative surgery.

    abstract::Few reports have investigated different genetic alterations according to age in various cancers. In total, 1749 GC patients receiving curative surgery were enrolled. The clinicopathological features, and prognoses were compared between younger (<65 years) and older (≥65 years) patients. Genetic mutations were analyzed...

    journal_title:Aging

    pub_type: 杂志文章

    doi:10.18632/aging.103627

    authors: Wu CW,Chen MH,Huang KH,Chang SC,Fang WL,Lin CH,Chao Y,Lo SS,Li AF,Shyr YM

    更新日期:2020-08-18 00:00:00