Abstract:
:While NLRP3-inflammasome has been implicated in cardiovascular diseases, its role in physiological cardiac aging is largely unknown. During aging, many alterations occur in the organism, which are associated with progressive impairment of metabolic pathways related to insulin resistance, autophagy dysfunction, and inflammation. Here, we investigated the molecular mechanisms through which NLRP3 inhibition may attenuate cardiac aging. Ablation of NLRP3-inflammasome protected mice from age-related increased insulin sensitivity, reduced IGF-1 and leptin/adiponectin ratio levels, and reduced cardiac damage with protection of the prolongation of the age-dependent PR interval, which is associated with atrial fibrillation by cardiovascular aging and reduced telomere shortening. Furthermore, old NLRP3 KO mice showed an inhibition of the PI3K/AKT/mTOR pathway and autophagy improvement, compared with old wild mice and preserved Nampt-mediated NAD+ levels with increased SIRT1 protein expression. These findings suggest that suppression of NLRP3 prevented many age-associated changes in the heart, preserved cardiac function of aged mice and increased lifespan.
journal_name
Aging Celljournal_title
Aging cellauthors
Marín-Aguilar F,Lechuga-Vieco AV,Alcocer-Gómez E,Castejón-Vega B,Lucas J,Garrido C,Peralta-Garcia A,Pérez-Pulido AJ,Varela-López A,Quiles JL,Ryffel B,Flores I,Bullón P,Ruiz-Cabello J,Cordero MDdoi
10.1111/acel.13050subject
Has Abstractpub_date
2020-01-01 00:00:00pages
e13050issue
1eissn
1474-9718issn
1474-9726journal_volume
19pub_type
杂志文章相关文献
AGING CELL文献大全abstract::The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in agi...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2011.00672.x
更新日期:2011-04-01 00:00:00
abstract::Mitochondrial dysfunction plays a key pathogenic role in aging skeletal muscle resulting in significant healthcare costs in the developed world. However, there is no pharmacologic treatment to rapidly reverse mitochondrial deficits in the elderly. Here, we demonstrate that a single treatment with the mitochondrial-tar...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12102
更新日期:2013-10-01 00:00:00
abstract::Hutchinson-Gilford Progeria Syndrome (HGPS) is a devastating premature aging disease. Mouse models have been instrumental for understanding HGPS mechanisms and for testing therapies, which to date have had only marginal benefits in mice and patients. Barriers to developing effective therapies include the unknown etiol...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12852
更新日期:2019-02-01 00:00:00
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
更新日期:2019-04-01 00:00:00
abstract::Older adults universally suffer from sarcopenia and approximately 60-70% are diabetic or prediabetic. Nonetheless, the mechanisms underlying these aging-related metabolic disorders are unknown. NFκB has been implicated in the pathogenesis of several aging-related pathologies including sarcopenia and type 2 diabetes an...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12613
更新日期:2017-08-01 00:00:00
abstract::Reactive oxygen species (ROS) play important signaling roles in metazoans, but also cause significant molecular damage. Animals tightly control ROS levels using sophisticated defense mechanisms, yet the transcriptional pathways that induce ROS defense remain incompletely understood. In the nematode Caenorhabditis eleg...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12154
更新日期:2014-02-01 00:00:00
abstract::Astrocytes participate in numerous aspects of central nervous system (CNS) physiology ranging from ion balance to metabolism, and disruption of their physiological roles can therefore be a contributor to CNS dysfunction and pathology. Cellular senescence, one of the mechanisms of aging, has been proposed as a central ...
journal_title:Aging cell
pub_type: 杂志文章,评审
doi:10.1111/acel.12937
更新日期:2019-06-01 00:00:00
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
更新日期:2012-10-01 00:00:00
abstract::Most mammalian cells when placed in culture will undergo a limited number of cell divisions before entering an unresponsive non-proliferating state termed senescence. However, several pathways that are activated singly or in concert can allow cells to bypass senescence at least for limited periods. These include the t...
journal_title:Aging cell
pub_type: 杂志文章,评审
doi:10.1111/j.1474-9728.2004.00134.x
更新日期:2004-12-01 00:00:00
abstract::Translation of RNA to protein is essential for life. It should perhaps not be surprising, therefore, that appropriate regulation of translation plays a key role in determining longevity. This Hot Topic article discusses papers published in the last year related to the importance of translation and its regulation by si...
journal_title:Aging cell
pub_type: 杂志文章,评审
doi:10.1111/j.1474-9726.2007.00341.x
更新日期:2007-12-01 00:00:00
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
更新日期:2019-06-01 00:00:00
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
更新日期:2014-06-01 00:00:00
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
更新日期:2007-06-01 00:00:00
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
更新日期:2019-06-01 00:00:00
abstract::Little is known about the types and numbers of mutations that may accumulate in normal human cells with age. Such information would require obtaining enough DNA from a single cell to accurately carry out reliable analysis despite extensive amplification; and complete genomic coverage under these circumstances is diffi...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12053
更新日期:2013-04-01 00:00:00
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
更新日期:2011-12-01 00:00:00
abstract::Despite its medical, social, and economic significance, understanding what primarily causes aging, that is, the mechanisms of the aging process, remains a fundamental and fascinating problem in biology. Accumulating evidence indicates that a small RNA-based gene regulatory machinery, the Piwi-piRNA pathway, represents...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12630
更新日期:2017-10-01 00:00:00
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
更新日期:2009-12-01 00:00:00
abstract::Neuropeptide Y (NPY) is an orexigenic peptide that plays an essential role in caloric restriction (CR)-mediated lifespan extension. However, the mechanisms underlying the NPY-mediated effects in CR are poorly defined. Here, we report that NPY deficiency in male mice during CR increases mortality in association with li...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12558
更新日期:2017-04-01 00:00:00
abstract::The transcription of ribosomal RNA genes (rDNA) is subject to epigenetic regulation, as it is abrogated by the methylation of CpG dinucleotides within their promoter region. Here, we investigated, through Sequenom platform, the age-related methylation status of the CpG island falling into the rDNA promoter in 472 bloo...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12603
更新日期:2017-10-01 00:00:00
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
更新日期:2020-11-01 00:00:00
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
更新日期:2017-12-01 00:00:00
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
更新日期:2013-12-01 00:00:00
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
更新日期:2010-04-01 00:00:00
abstract::Age-associated mitochondrial dysfunction and oxidative damage are primary causes for multiple health problems including sarcopenia and cardiovascular disease (CVD). Though the role of Nrf2, a transcription factor that regulates cytoprotective gene expression, in myopathy remains poorly defined, it has shown beneficial...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13261
更新日期:2020-11-01 00:00:00
abstract::Adipose tissue inflammation and dysfunction are associated with obesity-related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of dia...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12950
更新日期:2019-06-01 00:00:00
abstract::Replicative senescence has a major impact on function and integrity of cell preparations. This process is reflected by continuous DNA methylation (DNAm) changes at specific CpG dinucleotides in the course of in vitro culture, and such modifications can be used to estimate the state of cellular senescence for quality c...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12544
更新日期:2017-02-01 00:00:00
abstract::Cross-sectional studies have repeatedly suggested peripheral blood monocyte telomere length as a biomarker of aging. To test this suggestion in a large population-based follow-up study of the oldest old, we measured telomere length at baseline in 598 participants of the Leiden 85-plus Study (mean age at baseline 89.8 ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2005.00171.x
更新日期:2005-12-01 00:00:00
abstract::Intron retention (IR) is the least well-understood alternative splicing type in animals, and its prevalence and function in physiological and pathological processes have long been underestimated. Cellular senescence contributes to individual aging and age-related diseases and can also serve as an important cancer prev...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13276
更新日期:2020-12-01 00:00:00
abstract::Fat tissue, frequently the largest organ in humans, is at the nexus of mechanisms involved in longevity and age-related metabolic dysfunction. Fat distribution and function change dramatically throughout life. Obesity is associated with accelerated onset of diseases common in old age, while fat ablation and certain mu...
journal_title:Aging cell
pub_type: 杂志文章,评审
doi:10.1111/j.1474-9726.2010.00608.x
更新日期:2010-10-01 00:00:00