Abstract:
:Patients with X-linked lymphoproliferative syndrome (XLP) experience excessive T cell proliferation after primary Epstein-Barr virus (EBV) infection, due to mutations in the signalling lymphocyte activation molecule (SLAM) associated protein (SAP) molecule. We examined the impact of dysfunctional proliferative control on the extent of CD8+ T cell differentiation in XLP patients who recovered from primary EBV infection. Although these young patients have normal numbers of lytic and latent EBV-epitope-specific CD8+ T cells, they were extremely differentiated as defined by loss of CCR7 and CD27, low telomerase activity and very short telomeres. This was not a direct effect arising from the loss of SAP, but was due to excessive T cell stimulation due to this defect. Thus, transduction of XLP CD8+ T cells with the catalytic component of telomerase (hTERT), but not SAP, prevented telomere loss and considerably extended proliferative lifespan in vitro. These results indicate that excessive proliferation in CD8+ T cells in XLP patients may lead to end-stage differentiation and loss of functional EBV-specific CD8+ T cells through replicative senescence. This may contribute to the defective immunity found in XLP patients who survive acute EBV infection who develop EBV-related B cell lymphomas before the fourth decade of life.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Plunkett FJ,Franzese O,Belaramani LL,Fletcher JM,Gilmour KC,Sharifi R,Khan N,Hislop AD,Cara A,Salmon M,Gaspar HB,Rustin MH,Webster D,Akbar ANdoi
10.1016/j.mad.2005.03.006subject
Has Abstractpub_date
2005-08-01 00:00:00pages
855-65issue
8eissn
0047-6374issn
1872-6216pii
S0047-6374(05)00069-2journal_volume
126pub_type
杂志文章abstract::Rats of two age groups (6 weeks and 30 months) received (1) a single dose of 600 mg D-galactosamine (GalN)/kg body weight by intraperitoneal (i.p.) injection, (2) a single dose of 600 mg GalN/kg body weight i.p. combined with 20 mg prednisolone/kg body weight subcutaneously at the beginning of the experiment. The kine...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(78)90064-7
更新日期:1978-03-01 00:00:00
abstract::Previous reports suggest that 33 degrees C is the optimum temperature for the long-term culture of murine bone marrow in vitro. We found that horse serum was an important variable determining our ability to culture marrow from immature (less than 10 weeks) mice at 37 degrees C. While some batches supported growth othe...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(84)90179-9
更新日期:1984-01-01 00:00:00
abstract::In this review we discuss the yeast as a paradigm for the study of aging. The budding yeast Saccharomyces cerevisiae, which can proliferate in both haploid and diploid states, has been used extensively in aging research. The budding yeast divides asymmetrically to form a 'mother' cell and a bud. Two major approaches, ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/s0047-6374(00)00182-2
更新日期:2000-12-01 00:00:00
abstract::The present study aimed to reveal aging-related changes in the skeletal muscle of SD rats by comparing transcriptome analysis, integrated with muscle physiological parameters. Ten rats aged 25 months were set as the old group (OG) and ten rats aged 6 months were set as the young group (YG). After 6 weeks of feeding, t...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2018.01.001
更新日期:2018-01-01 00:00:00
abstract::Human diploid cells, TIG-7, were serially cultivated under 1%, 5% or 21% (air) oxygen. The limit of their cumulative population doublings was extended by 16% or 10% under 1% or 5% oxygen, respectively, as compared with that under 21% oxygen. When TIG-7 cells were serially cultivated in the presence of 10 mM or 20 mM 3...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(95)01584-m
更新日期:1995-07-14 00:00:00
abstract::A quantitative ultrastructural study of the posterior pituitary was undertaken. The posterior pituitary is the storage of the hormones vasopressin and oxytocin. Female C57BL/Icrfat mice which were under conditions of normal hydration were sampled at 8 and 32 months of age. There was a slight age-related decline in the...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(81)90069-5
更新日期:1981-02-01 00:00:00
abstract::The presence of damaged and microbial DNA can pose a threat to the survival of organisms. Cells express various sensors that recognize specific aspects of such potentially dangerous DNA. Recognition of damaged or microbial DNA by sensors induces cellular processes that are important for DNA repair and inflammation. He...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/j.mad.2016.09.001
更新日期:2017-07-01 00:00:00
abstract::The effects of aging on the activation of the cytoplasmic tyrosine protein kinase p56(lck) have been investigated in PBL from adult and elderly subjects upon activation with mitogens or different co-stimuli. Results show that the amount and phosphorylation of p56(lck) are reduced in PBL from elderly as compared to adu...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(97)00144-9
更新日期:1998-05-15 00:00:00
abstract::Mice with an overall deletion of the sensory neuropeptide α-calcitonin gene-related peptide (α-CGRP) develop an age-dependent osteopenic bone phenotype. Underlying molecular mechanisms of how αCGRP affects bone cell metabolism are not well understood. This study aims to characterize differences in metabolic parameters...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2020.111265
更新日期:2020-07-01 00:00:00
abstract::The healing of normal incisional wounds and ischemic flap wounds was investigated in young (10 weeks) and old (102-104 weeks) rats, together with the effect of treatment with hyperbaric oxygen on day 0-3 of healing. After 10 days of healing all biomechanical strength parameters of normal wounds were decreased by 30-40...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(96)01782-4
更新日期:1996-10-25 00:00:00
abstract::Age-dependent renal damage is influenced by genetic background and the Fisher344xBrown Norway (F344xBN) rat is resistant to glomerular injury. In vulnerable strains, a fall in renal nitric oxide synthase (NOS) contributes to age-dependent renal damage. Here, we investigated renal NOS in young (3 months) and old (30 mo...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2010.10.004
更新日期:2011-01-01 00:00:00
abstract::The activity of rat heart succinate dehydrogenase (SDH) increases 1.7-fold in old animals (Vitorica, J., Cano, J., Satrústegui, J. and Machado, A., Mech. Ageing Dev., 16 (1981) 105-116). This increase is due to an increase in enzyme protein itself because: (a) the activation state of the enzyme does not vary with age;...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(85)90076-4
更新日期:1985-11-01 00:00:00
abstract::As a prerequisite to investigating the specification and differentiation of cardiac tissue in vitro, the ontogeny of a number of putative cardiac-specific, and striated muscle-specific gene transcripts has been studied. The probes used include cDNAs of alpha-actins, myosin heavy chains, myosin light chains, alpha-trop...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(94)90019-1
更新日期:1994-12-16 00:00:00
abstract::A comparison was made of the resting membrane potential (MP) as well as the MP responses to K+, ACTH and gamma-MSH of superfused adrenocortical, zona fasciculata cells from young (Y) and old (O) male rats. The resting MP of these cells did not vary with age. However, the MP responses to altered extracellular [K+] vari...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(88)90036-x
更新日期:1988-06-01 00:00:00
abstract::As measured by X-ray microanalysis of frozen-dried cryosections, physiological concentrations of phosphorus, Na+, K+ and Mg2+ show a biphasic age dependence in some compartments of rat hepatocytes, especially in the regions of condensed chromatin associated with the actively transcribed genes. This could be consistent...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(87)90077-7
更新日期:1987-04-01 00:00:00
abstract::The impairment of brown adipose tissue (BAT) thermogenic activity with aging has been well documented. The current study investigated the effect of swimming training on BAT activity in 2-month-old (young) and 26-month-old (old) male mice. The trained mice underwent a 6-week swimming program (1 h/day, 5 days/week) in w...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(96)01727-7
更新日期:1996-08-15 00:00:00
abstract::Glucose phosphorylating activity of human erythrocytes quickly decreases during cell ageing; the electrophoretic pattern suggests that this fast decrease is due mainly to the isozyme II. We have shown that in the young cells only hexokinase I and II are responsible for the glucose phosphorylation, while in the old cel...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(78)90024-6
更新日期:1978-10-01 00:00:00
abstract::Hormone responsiveness is mediated by signal transduction mechanisms involving second messengers, such as cAMP and Ca2+, which regulate reversible changes in the phosphorylation state of proteins. During senescence individuals frequently exhibit a diminished responsiveness to hormones. We examined changes in enzymes i...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(88)90125-x
更新日期:1988-12-01 00:00:00
abstract::The number of senescent cells in the skin is increasing with age. Numerous studies have attempted to elucidate the role of these cells in normal aging of the skin as well as in age-related skin conditions. In recent years, attempts have also been made to find treatments that aim either to cleanse the skin tissues of s...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/j.mad.2020.111409
更新日期:2021-01-01 00:00:00
abstract::We compared cardiovascular responses to various adrenergic agonists in conscious 3-month and 12-month old rats that had been treated with propranolol daily for 7 days, to determine whether changes in beta-adrenergic hypersensitivity induced by abrupt propranolol withdrawal would differ with age. Depressor and tachycar...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(92)90019-a
更新日期:1992-03-15 00:00:00
abstract::Hepatocytes isolated from 6-, 12-, 18-, and 30-month-old female Fischer F344 rats were examined by scanning electron microscopy. No significant change in cell size with age was observed. However, the surface morphology of the cells isolated from the older animals exhibited a significant increase in surface folds. This...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(81)90023-3
更新日期:1981-01-01 00:00:00
abstract::Lipofuscin-specific autofluorescence of living, cultured rat neonatal myocardial myocytes was studied with respect to intensity and spectral characteristics. The autofluorescence emission spectrum changed over time indicating continuously ongoing intramolecular reorganisation of the pigment. Moreover, as compared with...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(94)90040-x
更新日期:1994-01-01 00:00:00
abstract::A few reports suggest that pigmented granules found in molluscan neurons accumulate with age as do lipofuscin granules in vertebrate cells; however, no reports on molluscan neurons include detailed descriptions of granule accumulation or histochemical tests to identify the pigment as lipofuscin-like. In this study lig...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(78)90052-0
更新日期:1978-01-01 00:00:00
abstract::A subset of 43 [35S]methionine labeled mitochondrial proteins, identified on two dimensional electrophoresis gels of whole body extracts of adult Drosophila, were compared between two age groups. These flies, which except for their spermatocytes consist entirely of postmitotic cells, were 6 days old and 38 days old, w...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(86)90105-3
更新日期:1986-03-01 00:00:00
abstract::The data concerning the effects of age on the brainstem are scarce and few works are devoted to the human vestibular nuclear complex. The study of the effects of aging in the vestibular nuclei could have clinical interest due to the high prevalence of balance control and gait problems in the elderly. We have used in t...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(00)00098-1
更新日期:2000-04-14 00:00:00
abstract::We tested the hypothesis that Ca(2+)-activated myosin ATPase activity is lower in muscles of aged rats relative to muscles of young rats, independent of changes in myosin isoform expression. Myofibrils were prepared from permeabilized fibers of soleus, plantaris, and semimembranosus muscles of young (8-12 months) and ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2004.07.002
更新日期:2004-09-01 00:00:00
abstract::The influence of age on liver gene expression was investigated in two strains of H-2 congenic mice. In B10.RIII mice (H-2r), basal P1- and P3-450 RNA levels progressively decreased 65 and 95%, respectively, between 4 and 28 months of age (P less than or equal to 0.05). Polyaromatic hydrocarbon (PAH) induced P1- and P3...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(90)90038-h
更新日期:1990-03-31 00:00:00
abstract::Different theories of ageing exist. Oxidative stress by generating neo-antigens and affecting cellular communications may precipitate immune disregulation, and both may concur in the whole ageing process. In the present study, we have analysed the effect of dietary high doses of vitamin E, a free radical scavenger, on...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(94)91593-8
更新日期:1994-10-20 00:00:00
abstract::Senescence is a biological process that induces a permanent cell cycle arrest and a specific gene expression program in response to various stressors. Following studies over the last few decades, the concept of senescence has evolved from an antiproliferative mechanism in cancer (oncogene-induced senescence) to a crit...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2020.111411
更新日期:2020-12-09 00:00:00
abstract::Age is the only one non-modifiable risk of cerebral ischemia. Advances in stroke medicine and behavioral adaptation to stroke risk factors and comorbidities was successful in decreasing stroke incidence and increasing the number of stroke survivors in western societies. Comorbidities aggravates the outcome after cereb...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/j.mad.2020.111312
更新日期:2020-09-01 00:00:00