Abstract:
:The ING family of tumor suppressor proteins affects cell growth, apoptosis and response to DNA damage by modulating chromatin structure through association with different HAT and HDAC complexes. The major splicing isoforms of the ING1 locus are ING1a and INGlb. While INGlb plays a role in inducing apoptosis, the function of ING1a is currently unknown. Here we show that alternative splicing of the ING1 message alters the INGla:INGlb ratio by approximately 30-fold in senescent compared to low passage primary fibroblasts. INGla antagonizes INGlb function in apoptosis, induces the formation of structures resembling senescence-associated heterochromatic foci containing heterochromatin protein 1 gamma, the accumulation of senescence-associated beta-galactosidase activity and promotes senescent cell morphology and cell cycle arrest. Phenotypic effects may result from differential effects on gene expression since ING1a increases levels of both retinoblastoma and the p16 cyclin-dependent kinase inhibitor and ING1a and ING1b have opposite effects on the expression of proliferating nuclear cell antigen (PCNA), which is required for cell growth. Gene expression appears to be altered by targeting of HDAC complexes to gene promoters since INGla associates with several-fold higher levels of HDAC1 in senescent, compared to replication-competent cells and ING1 is found on the PCNA promoter by chromatin immunoprecipitation analysis. These data demonstrate a novel role for the ING1 proteins in differentially regulating senescence-associated chromatin remodeling vs. apoptosis and support the idea that altered ratios of the ING1 splicing isoforms may contribute to establishing the senescent phenotype through HDAC and HAT complex-mediated effects on chromatin structure.
journal_name
Aging Celljournal_title
Aging cellauthors
Soliman MA,Berardi P,Pastyryeva S,Bonnefin P,Feng X,Colina A,Young D,Riabowol Kdoi
10.1111/j.1474-9726.2008.00427.xsubject
Has Abstractpub_date
2008-12-01 00:00:00pages
783-94issue
6eissn
1474-9718issn
1474-9726pii
ACE427journal_volume
7pub_type
杂志文章相关文献
AGING CELL文献大全abstract::Most human tissues express low levels of telomerase and undergo telomere shortening and eventual senescence; the resulting limitation on tissue renewal can lead to a wide range of age-dependent pathophysiologies. Increasing evidence indicates that the decline in cell division capacity in cells that lack telomerase can...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12099
更新日期:2013-08-01 00:00:00
abstract::Ubiquitously reduced signaling via Methuselah (MTH), a G-protein-coupled receptor (GPCR) required for neurosecretion, has previously been reported to extend life and enhance stress resistance in flies. Whether these effects are due to reduced MTH signalling in specific tissues remains unknown. We determined that reduc...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12027
更新日期:2013-02-01 00:00:00
abstract::SARS-CoV-2 is a novel betacoronavirus which infects the lower respiratory tract and can cause coronavirus disease 2019 (COVID-19), a complex respiratory distress syndrome. Epidemiological data show that COVID-19 has a rising mortality particularly in individuals with advanced age. Identifying a functional association ...
journal_title:Aging cell
pub_type: 杂志文章,评审
doi:10.1111/acel.13237
更新日期:2020-10-01 00:00:00
abstract::Although dietary restriction (DR) is known to extend lifespan across species, from yeast to mammals, the signalling events downstream of food/nutrient perception are not well understood. In Caenorhabditis elegans, DR is typically attained either by using the eat-2 mutants that have reduced pharyngeal pumping leading t...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12218
更新日期:2014-08-01 00:00:00
abstract::Klotho is a recently discovered anti-aging gene. The purpose of this study was to investigate whether klotho gene transfer attenuates superoxide production and oxidative stress in rat aorta smooth muscle (RASM) cells. RASM cells were transfected with AAV plasmids carrying mouse klotho full-length cDNA (mKL) or LacZ as...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2012.00796.x
更新日期:2012-06-01 00:00:00
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
更新日期:2017-08-01 00:00:00
abstract::Aging causes profound effects on the hematopoietic stem cell (HSC) pool, including an altered output of mature progeny and enhanced self-propagation of repopulating-defective HSCs. An important outstanding question is whether HSCs can be protected from aging. The signal adaptor protein LNK negatively regulates hematop...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2012.00863.x
更新日期:2012-12-01 00:00:00
abstract::Small body size has been associated with long life span in four stocks of mutant dwarf mice, and in two varieties of dietary restriction in rodents. In this study, small body size at ages 2-24 months was shown to be a significant predictor of life span in a genetically heterogeneous mouse population derived from four ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1046/j.1474-9728.2002.00006.x
更新日期:2002-10-01 00:00:00
abstract::Aging is inevitably accompanied by gradual and irreversible innate endothelial dysfunction. In this study, we tested the hypothesis that accentuation of glucose metabolism via the aldose reductase (AR) pathway contributes to age-related vascular dysfunction. AR protein and activity levels were significantly increased ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2010.00606.x
更新日期:2010-10-01 00:00:00
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
更新日期:2015-06-01 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::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
更新日期:2015-12-01 00:00:00
abstract::Oxidative modification of cellular components may contribute to tissue dysfunction during aging. In skeletal muscle, contractile activity increases the generation of reactive oxygen and nitrogen species (ROS). The question of whether contraction-induced ROS generation is further increased in skeletal muscle of the eld...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2006.00198.x
更新日期:2006-04-01 00:00:00
abstract::Inhibition of mammalian target of rapamycin, mTOR, extends lifespan and reduces age-related disease. It is not known what role mTOR plays in the arterial aging phenotype or if mTOR inhibition by dietary rapamycin ameliorates age-related arterial dysfunction. To explore this, young (3.8 ± 0.6 months) and old (30.3 ± 0....
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12524
更新日期:2017-02-01 00:00:00
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
更新日期:2010-06-01 00:00:00
abstract::Impaired osteoblast function is involved in osteoporosis, and microRNA (miRNA) dysregulation may cause abnormal osteoblast osteogenic activity. However, the influence of miRNA on osteoblast activity and the underlying mechanisms remain elusive. In this study, miR-103-3p was found to be negatively correlated with bone ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13298
更新日期:2021-01-13 00:00:00
abstract::Age-related bone loss in mice results from a decrease in bone formation and an increase in cortical bone resorption. The former is accounted by a decrease in the number of postmitotic osteoblasts which synthesize the bone matrix and is thought to be the consequence of age-dependent changes in mesenchymal osteoblast pr...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12597
更新日期:2017-08-01 00:00:00
abstract::Aging causes cardiac dysfunction, often leading to heart failure and death. The molecular basis of age-associated changes in cardiac structure and function is largely unknown. The fruit fly, Drosophila melanogaster, is well-suited to investigate the genetics of cardiac aging. Flies age rapidly over the course of weeks...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12559
更新日期:2017-02-01 00:00:00
abstract::Here I comment on the recent contribution by Barrientos et al. J. Neurosci. 32, 14641-14648 (2012) addressing treatment possibilities for surgery-induced cognitive dysfunction. It has been over 15 years since the publication of a landmark study that indicated age as a major risk factor for postoperative cognitive dysf...
journal_title:Aging cell
pub_type: 评论,杂志文章
doi:10.1111/acel.12066
更新日期:2013-06-01 00:00:00
abstract::A huge amount of evidence has implicated amyloid beta (A beta) peptides and other derivatives of the amyloid precursor protein (beta APP) as central to the pathogenesis of Alzheimer's disease (AD). It is also widely recognized that age is the most important risk factor for AD and that the innate immune system plays a ...
journal_title:Aging cell
pub_type: 杂志文章,评审
doi:10.1111/j.1474-9728.2004.00101.x
更新日期:2004-08-01 00:00:00
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
更新日期:2012-04-01 00:00:00
abstract::Chromatin structure affects the accessibility of DNA to transcription, repair, and replication. Changes in chromatin structure occur during development, but less is known about changes during aging. We examined the state of chromatin structure and its effect on gene expression during aging in Drosophila at the whole g...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2010.00624.x
更新日期:2010-12-01 00:00:00
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
更新日期:2014-04-01 00:00:00
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
更新日期:2015-10-01 00:00:00
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
更新日期:2010-10-01 00:00:00
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
更新日期:2018-06-01 00:00:00
abstract::One of the hallmarks of aging is the progressive accumulation of senescent cells in organisms, which has been proposed to be a contributing factor to age-dependent organ dysfunction. We recently reported that Bruton's tyrosine kinase (BTK) is an upstream component of the p53 responses to DNA damage. BTK binds to and p...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13079
更新日期:2020-01-01 00:00:00
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
更新日期:2010-08-01 00:00:00
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
更新日期:2008-01-01 00:00:00
abstract::Growth hormone receptor knockout (GHRKO) mice are remarkably long-lived and have improved glucose homeostasis along with altered energy metabolism which manifests through decreased respiratory quotient (RQ) and increased oxygen consumption (VO2 ). Short-term exposure of these animals to increased environmental tempera...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13123
更新日期:2020-05-01 00:00:00