Abstract:
:The susceptibility of human CD4+ and CD8+ T cells to senesce differs, with CD8+ T cells acquiring an immunosenescent phenotype faster than the CD4+ T cell compartment. We show here that it is the inherent difference in mitochondrial content that drives this phenotype, with senescent human CD4+ T cells displaying a higher mitochondrial mass. The loss of mitochondria in the senescent human CD8+ T cells has knock-on consequences for nutrient usage, metabolism and function. Senescent CD4+ T cells uptake more lipid and glucose than their CD8+ counterparts, leading to a greater metabolic versatility engaging either an oxidative or a glycolytic metabolism. The enhanced metabolic advantage of senescent CD4+ T cells allows for more proliferation and migration than observed in the senescent CD8+ subset. Mitochondrial dysfunction has been linked to both cellular senescence and aging; however, it is still unclear whether mitochondria play a causal role in senescence. Our data show that reducing mitochondrial function in human CD4+ T cells, through the addition of low-dose rotenone, causes the generation of a CD4+ T cell with a CD8+ -like phenotype. Therefore, we wish to propose that it is the inherent metabolic stability that governs the susceptibility to an immunosenescent phenotype.
journal_name
Aging Celljournal_title
Aging cellauthors
Callender LA,Carroll EC,Bober EA,Akbar AN,Solito E,Henson SMdoi
10.1111/acel.13067subject
Has Abstractpub_date
2020-02-01 00:00:00pages
e13067issue
2eissn
1474-9718issn
1474-9726journal_volume
19pub_type
杂志文章相关文献
AGING CELL文献大全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::Astrocytes are key cells in brain aging, helping neurons to undertake healthy aging or otherwise letting them enter into a spiral of neurodegeneration. We aimed to characterize astrocytes cultured from senescence-accelerated prone 8 (SAMP8) mice, a mouse model of brain pathological aging, along with the effects of cal...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12259
更新日期:2015-06-01 00:00:00
abstract::Cellular senescence plays both beneficial and detrimental roles in embryonic development and tissue regeneration, while the underlying mechanism remains elusive. Recent studies disclosed the emerging roles of heat-shock proteins in regulating muscle regeneration and homeostasis. Here, we found that Hsp90β, but not Hsp...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13003
更新日期:2019-10-01 00:00:00
abstract::Protein synthesis is a regulated cellular process that links nutrients in the environment to organismal growth and development. Here we examine the role of genes that regulate mRNA translation in determining growth, reproduction, stress resistance and lifespan. Translational control of protein synthesis by regulators ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2006.00266.x
更新日期:2007-02-01 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::Current knowledge indicates that the adult mammalian retina lacks regenerative capacity. Here, we show that the adult stem cell marker, leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), is expressed in the retina of adult mice. Lgr5(+) cells are generated at late stages of retinal development and exh...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12346
更新日期:2015-08-01 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::Long-term calorie restriction (CR) has numerous benefits; however, effects of CR on susceptibility to intact pathogens are not well understood. Because CR enhances immune function of laboratory mice (Mus musculus), it was hypothesized that mice subjected to CR would be less susceptible to experimental infections of th...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2007.00345.x
更新日期:2007-12-01 00:00:00
abstract::General locomotor activity decreases with normal aging in animals and could be partially explained by decreases in neuronal function. Voltage-gated Na(+) channels are essential in initiating and propagating rapid electrical impulses underlying normal locomotor activity and behavior in animals. Isolation of mutations c...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2008.00368.x
更新日期:2008-03-01 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::Impaired insulin/IGF1 signalling has been shown to extend lifespan in model organisms ranging from yeast to mammals. Here we sought to determine the effect of targeted disruption of the insulin receptor (IR) in non-neuronal tissues of adult mice on the lifespan. We induced hemizygous (PerIRKO+/- ) or homozygous (PerIR...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12610
更新日期:2017-08-01 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::Brain mitochondrial function has been posited to decline with aging. In order to test this hypothesis, cortical and striatal mitochondria were isolated from Fischer 344 rats at 2, 5, 11, 24 and 33 months of age. Mitochondrial membrane potential remained stable through 24 months, declining slightly in mitochondria from...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2005.00156.x
更新日期:2005-06-01 00:00:00
abstract::The mitochondrial theory of aging is based around the idea of a vicious cycle, in which somatic mutation of mtDNA engenders respiratory chain dysfunction, enhancing the production of DNA-damaging oxygen radicals. In turn, this is proposed to result in the accumulation of further mtDNA mutations. Finally, a bioenergeti...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1046/j.1474-9728.2003.00032.x
更新日期:2003-02-01 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::Heart failure with preserved ejection fraction (HFpEF) is the most common type of HF in older adults. Although no pharmacological therapy has yet improved survival in HFpEF, exercise training (ExT) has emerged as the most effective intervention to improving functional outcomes in this age-related disease. The molecula...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13159
更新日期:2020-06-01 00:00:00
abstract::In a previous study, we reported that a deficiency in MnSOD activity (approximately 80% reduction) targeted to type IIB skeletal muscle fibers was sufficient to elevate oxidative stress and to reduce muscle function in young adult mice (TnIFastCreSod2(fl/fl) mice). In this study, we used TnIFastCreSod2(fl/fl) mice to ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2011.00695.x
更新日期:2011-06-01 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::Frailty is a state of decreased physiological reserve and increased vulnerability to adverse outcomes in aging, and is characterized by dysregulation across various biological pathways. Frailty may manifest biologically as alteration in protein expression, possibly regulated at genetic, transcriptional and epigenetic ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13193
更新日期:2020-09-01 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::A serum biomarker of biological versus chronological age would have significant impact on clinical care. It could be used to identify individuals at risk of early-onset frailty or the multimorbidities associated with old age. It may also serve as a surrogate endpoint in clinical trials targeting mechanisms of aging. H...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12706
更新日期:2018-04-01 00:00:00
abstract::Diabetes mellitus (DM) is one of the most devastating diseases that currently affects the aging population. Recent evidence indicates that DM is a risk factor for many brain disorders, due to its direct effects on cognition. New findings have shown that the microtubule-associated protein tau is pathologically processe...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12919
更新日期:2019-06-01 00:00:00
abstract::Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent a promising therapeutic tool for many diseases, including aged tissues and organs at high risk of failure. However, the intrinsic self-renewal and pluripotency of ES and iPS cells make them tumorigenic, and hence, the risk of tumor developmen...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2011.00754.x
更新日期:2012-02-01 00:00:00
abstract::The discovery of treatments to prevent or delay dementia and Alzheimer's disease is a priority. The gene APOE is associated with cognitive change and late-onset Alzheimer's disease, and epidemiological studies have provided strong evidence that the e2 allele of APOE has a neuroprotective effect, it is associated with ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13023
更新日期:2019-12-01 00:00:00
abstract::Calorie restriction (CR) without malnutrition slows aging in animal models. Oxidative stress reduction was proposed to mediate CR effects. CR effect on urinary F2-isoprostanes, validated oxidative stress markers, was assessed in CALERIE, a two-year randomized controlled trial. Healthy volunteers (n = 218) were randomi...
journal_title:Aging cell
pub_type: 杂志文章,随机对照试验
doi:10.1111/acel.12719
更新日期:2018-04-01 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::FOXO transcription factors (FOXOs) are central regulators of lifespan across species, yet they also have cell-specific functions, including adult stem cell homeostasis and immune function. Direct targets of FOXOs have been identified genome-wide in several species and cell types. However, whether FOXO targets are spec...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12479
更新日期:2016-08-01 00:00:00
abstract::Here, we report that inactivation of the Caenorhabditis elegans dynamin-related protein DRP-1, a key component responsible for mitochondrial fission and conserved from yeast to humans, dramatically enhanced the effect of reduced insulin signaling (IIS) to extend lifespan. This represents the first report of a benefici...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2011.00711.x
更新日期:2011-08-01 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::The age-associated decline of immune responses causes high susceptibility to infections and reduced vaccine efficacy in the elderly. However, the mechanisms underlying age-related deficits are unclear. Here, we found that the expression and signaling of flagellin (FlaB)-dependent Toll-like receptor 5 (TLR5), unlike th...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12383
更新日期:2015-10-01 00:00:00