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 be influenced by numerous genetic factors. Here, we use telomerase-defective strains of budding yeast to probe whether replicative senescence can be attenuated or accelerated by defects in factors previously implicated in handling of DNA termini. We show that the MRX (Mre11-Rad50-Xrs2) complex, as well as negative (Rif2) and positive (Tel1) regulators of this complex, comprise a single pathway that promotes replicative senescence, in a manner that recapitulates how these proteins modulate resection of DNA ends. In contrast, the Rad51 recombinase, which acts downstream of the MRX complex in double-strand break (DSB) repair, regulates replicative senescence through a separate pathway operating in opposition to the MRX-Tel1-Rif2 pathway. Moreover, defects in several additional proteins implicated in DSB repair (Rif1 and Sae2) confer only transient effects during early or late stages of replicative senescence, respectively, further suggesting that a simple analogy between DSBs and eroding telomeres is incomplete. These results indicate that the replicative capacity of telomerase-defective yeast is controlled by a network comprised of multiple pathways. It is likely that telomere shortening in telomerase-depleted human cells is similarly under a complex pattern of genetic control; mechanistic understanding of this process should provide crucial information regarding how human tissues age in response to telomere erosion.
journal_name
Aging Celljournal_title
Aging cellauthors
Ballew BJ,Lundblad Vdoi
10.1111/acel.12099subject
Has Abstractpub_date
2013-08-01 00:00:00pages
719-27issue
4eissn
1474-9718issn
1474-9726journal_volume
12pub_type
杂志文章相关文献
AGING CELL文献大全abstract::Previously, we reported that persistent DNA damage accelerates ageing of the spine, but the mechanisms behind this process are not well understood. Ataxia telangiectasia mutated (ATM) is a protein kinase involved in the DNA damage response, which controls cell fate, including cell death. To test the role of ATM in the...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13162
更新日期:2020-07-01 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::Alzheimer's disease (AD) is characterized clinically by memory loss and cognitive decline. Protein kinase A (PKA)-CREB signaling plays a critical role in learning and memory. It is known that glucose uptake and O-GlcNAcylation are reduced in AD brain. In this study, we found that PKA catalytic subunits (PKAcs) were po...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12449
更新日期:2016-06-01 00:00:00
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
更新日期:2004-12-01 00:00:00
abstract::The accumulation of mitochondrial DNA (mtDNA) mutations has been proposed as an underlying cause of the aging process. Such mutations are thought to be generated principally through mechanisms involving oxidative stress. Skin is frequently exposed to a potent mutagen in the form of ultraviolet (UV) radiation and mtDNA...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2007.00310.x
更新日期:2007-08-01 00:00:00
abstract::The bodily decline that occurs with advancing age strongly impacts on the prospects for future health and life expectancy. Despite the profound role of age in disease etiology, knowledge about the molecular mechanisms driving the process of aging in humans is limited. Here, we used an integrative network-based approac...
journal_title:Aging cell
pub_type: 杂志文章,meta分析
doi:10.1111/acel.12160
更新日期:2014-04-01 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::Cockayne syndrome (CS) is a rare hereditary multisystem disease characterized by neurological and development impairment, and premature aging. Cockayne syndrome cells are hypersensitive to oxidative stress, but the molecular mechanisms involved remain unresolved. Here we provide the first evidence that primary fibrobl...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2012.00815.x
更新日期:2012-06-01 00:00:00
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
更新日期:2005-04-01 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::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::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::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
更新日期:2010-10-01 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::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::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::Summary We address the problem of establishing a survival schedule for wild populations. A demographic key identity is established, leading to a method whereby age-specific survival and mortality can be deduced from a marked cohort life table established for individuals that are randomly sampled at unknown age and mar...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9728.2004.00096.x
更新日期:2004-06-01 00:00:00
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
更新日期:2018-06-01 00:00:00
abstract::Checkpoint kinase 2 (CHK2) is a downstream effector of the DNA damage response (DDR). Dysfunctional telomeres, either owing to critical shortening or disruption of the shelterin complex, activate a DDR, which eventually results in cell cycle arrest, senescence and/or apoptosis. Successive generations of telomerase-def...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12237
更新日期:2014-10-01 00:00:00
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
更新日期:2016-08-01 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::Accumulating evidence suggests a role for microRNAs (miRNAs) in regulating various processes of mammalian postnatal development and aging. To investigate the changes in blood-based miRNA expression from preterm infants to adulthood, we compared 365 miRNA expression profiles in a screening set of preterm infants and ad...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12225
更新日期:2014-08-01 00:00:00
abstract::Little is known about how diet and energy metabolism interact in determination of lifespan under ad libitum feeding. From 12 weeks of age until death, male and female wild-type (WT) and transgenic (TG) mice with increased skeletal muscle mitochondrial uncoupling (HSA-mUCP1 mice) were fed one of three different semisyn...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2010.00648.x
更新日期:2011-02-01 00:00:00
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
更新日期:2008-12-01 00:00:00
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
更新日期:2014-10-01 00:00:00
abstract::Mitochondrial DNA (mtDNA) deletions occur sporadically in zygotic and somatic tissues and reach their highest concentration in substantia nigra. Previously, we noted the increase of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) transcript by microarray in multiple cells and tissues bearing deletion...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2007.00323.x
更新日期:2007-10-01 00:00:00
abstract::Lifespan varies dramatically among species, but the biological basis is not well understood. Previous studies in model organisms revealed the importance of nutrient sensing, mTOR, NAD/sirtuins, and insulin/IGF1 signaling in lifespan control. By studying life-history traits and transcriptomes of 14 Drosophila species d...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12740
更新日期:2018-08-01 00:00:00
abstract::In this work we report that carnitines, in particular acetyl-l-carnitine (ALC), are able to prolong the chronological aging of yeast cells during the stationary phase. Lifespan extension is significantly reduced in yca1 mutants as well in rho(0) strains, suggesting that the protective effects pass through the Yca1 cas...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2010.00587.x
更新日期:2010-08-01 00:00:00
abstract::Incidence of intracerebral hemorrhage (ICH) and brain iron accumulation increases with age. Excess iron accumulation in brain tissues post-ICH induces oxidative stress and neuronal damage. However, the mechanisms underlying iron deregulation in ICH, especially in the aged ICH model have not been well elucidated. Ferro...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13235
更新日期:2020-11-01 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