Abstract:
:With reduced thymic activity, the population of naïve T cells in humans is maintained by homeostatic proliferation throughout adult life. In young adults, naïve CD4 T cells have enormous proliferative potential and plasticity to differentiate into different lineages. Here, we explored whether naïve CD4 T-cell aging is associated with a partial loss of this unbiased multipotency. We find that naïve CD4 T cells from older individuals have developed a propensity to develop into TH9 cells. Two major mechanisms contribute to this predisposition. First, responsiveness to transforming growth factor β (TGFβ) stimulation is enhanced with age due to an upregulation of the TGFβR3 receptor that results in increased expression of the transcription factor PU.1. Secondly, aged naïve CD4 T cells display altered transcription factor profiles in response to T-cell receptor stimulation, including enhanced expression of BATF and IRF4 and reduced expression of ID3 and BCL6. These transcription factors are involved in TH9 differentiation as well as IL9 transcription suggesting that the aging-associated changes in the transcription factor profile favor TH9 commitment.
journal_name
Aging Celljournal_title
Aging cellauthors
Hu B,Li G,Ye Z,Gustafson CE,Tian L,Weyand CM,Goronzy JJdoi
10.1111/acel.12957subject
Has Abstractpub_date
2019-08-01 00:00:00pages
e12957issue
4eissn
1474-9718issn
1474-9726journal_volume
18pub_type
杂志文章相关文献
AGING CELL文献大全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::Dietary restriction (DR) is the most universal intervention known to extend animal lifespan. DR also prevents tumor development in mammals, and this effect requires the tumor suppressor PTEN. However, the metabolic and cellular processes that underly the beneficial effects of DR are poorly understood. We identified sl...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2010.00640.x
更新日期:2011-02-01 00:00:00
abstract::Skin hair follicles (HF) contain bulge stem cells (SC) that regenerate HFs during hair cycles, and repair skin epithelia following injury. As natural aging is associated with decreased skin repair capacity in humans, we have investigated the impact of age on human scalp HF bulge cell number and function. Here, we isol...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2009.00526.x
更新日期:2009-12-01 00:00:00
abstract::Dietary restriction (DR) increases lifespan and attenuates age-related phenotypes in many organisms; however, the effect of DR on longevity of individuals in genetically heterogeneous populations is not well characterized. Here, we describe a large-scale effort to define molecular mechanisms that underlie genotype-spe...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12130
更新日期:2013-12-01 00:00:00
abstract::Pairing two animals in parabiosis to test for systemic or circulatory factors from one animal affecting the other animal has been used in scientific studies for at least 150 years. These studies have led to advances in fields as diverse as endocrinology, immunology, and oncology. A variation on the technique, heteroch...
journal_title:Aging cell
pub_type: 杂志文章,评审
doi:10.1111/acel.12065
更新日期:2013-06-01 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::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::In this, the fourth installment of our annual Hot Topics review on mRNA translation and aging, we have decided to expand our scope to include recent findings related to the role of TOR signaling in aging. As new data emerge, it is clear that TOR signaling acts upstream of mRNA translation, as well as a variety of othe...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2010.00665.x
更新日期:2011-04-01 00:00:00
abstract::Recent reports highlight regulatory functions of long noncoding RNAs (lncRNAs) in neurodegeneration and aging, but biomedical implications remain limited. Here, we report an rRNA-depletion-based long RNA-Sequencing Resource of 65 substantia nigra, amygdala, and medial temporal gyrus samples from Parkinson's disease (P...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13115
更新日期:2020-03-01 00:00:00
abstract::Over the last 10 years, various screens of small molecules have been conducted to find long sought interventions in aging. Most of these studies were performed in invertebrates but the demonstration of pharmacological lifespan extension in the mouse has created considerable excitement. Since aging is a common risk fac...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2012.00789.x
更新日期:2012-04-01 00:00:00
abstract::The COVID-19 coronavirus is now spreading worldwide. Its pathogen, SARS-CoV-2, has been shown to use angiotensin-converting enzyme 2 (ACE2) as its host cell receptor, same as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. Epidemiology studies found males although only slightly more likely to be ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13168
更新日期:2020-07-01 00:00:00
abstract::Evidence suggests that muscarinic receptors (MAChRs) are involved in various aspects of neuronal and vascular functioning, and that there is selective oxidative stress sensitivity (OSS) among MAChR subtypes. COS-7 cells transfected with M1, M2 and M4 subtypes show greater OSS than the M1 and M3 subtypes, as seen by th...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9728.2004.00123.x
更新日期:2004-10-01 00:00:00
abstract::Dietary restriction extends lifespan and inhibits reproduction in many species. In Caenorhabditis elegans, inhibiting reproduction by germline removal extends lifespan. Therefore, we asked whether the effect of dietary restriction on lifespan might proceed via changes in the activity of the germline. We found that die...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2007.00327.x
更新日期:2007-10-01 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::Histone acetyltransferases (HATs) are important enzymes that transfer acetyl groups onto histones and thereby regulate both gene expression and chromosomal structures. Previous work has shown that the activation of sirtuins, which are histone deacetylases, can extend lifespan. This suggests that inhibiting HATs may ha...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13129
更新日期:2020-04-01 00:00:00
abstract::Methionine restriction (MetR) extends lifespan across different species and exerts beneficial effects on metabolic health and inflammatory responses. In contrast, certain cancer cells exhibit methionine auxotrophy that can be exploited for therapeutic treatment, as decreasing dietary methionine selectively suppresses ...
journal_title:Aging cell
pub_type: 杂志文章,评审
doi:10.1111/acel.13034
更新日期:2019-12-01 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::Increasing evidence suggests that regulation of heterochromatin at the nuclear envelope underlies metabolic disease susceptibility and age-dependent metabolic changes, but the mechanism is unknown. Here, we profile lamina-associated domains (LADs) using lamin B1 ChIP-Seq in young and old hepatocytes and find that, alt...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12742
更新日期:2018-06-01 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::The aim of this study was to investigate changes in astrocyte density, morphology, proliferation and apoptosis occurring in the central nervous system during physiological aging. Astrocytes in retinal whole-mount preparations from Wistar rats aged 3 (young adult) to 25 months (aged) were investigated qualitatively and...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2008.00402.x
更新日期:2008-08-01 00:00:00
abstract::Upon oxidative challenge the genome accumulates adducts and breaks that activate the DNA damage response to repair, arrest, or eliminate the damaged cell. Thus, reactive oxygen species (ROS) generated by endogenous oxygen metabolism are thought to affect mutation frequency. However, few studies determined the mutation...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12036
更新日期:2013-04-01 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::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::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::Aging is commonly associated with a structural deterioration of skin that compromises its barrier function, healing, and susceptibility to disease. Several lines of evidence show that these changes are driven largely by impaired tissue mitochondrial metabolism. While exercise is associated with numerous health benefit...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12341
更新日期:2015-08-01 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::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::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::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::Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that ha...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12039
更新日期:2013-04-01 00:00:00