Abstract:
:The cerebellum is exquisitely sensitive to deficiencies in the cellular response to specific DNA lesions. Genetic disorders caused by such deficiencies involve relentless, progressive cerebellar atrophy with striking loss of Purkinje and granule neurons. The reason for the extreme sensitivity of these cells to defective response to certain DNA lesions is unclear. This is particularly true for ataxia-telangiectasia (A-T) - a genomic instability syndrome whose major symptom is cerebellar atrophy. It is important to understand whether the DNA damage response in the cerebellum, particularly in Purkinje neurons, has special characteristics that stem from the unique features of these cells. Murine cerebellar organotypic cultures provide a valuable experimental system for this purpose since they retain the tissue organization for several weeks in culture and appear to provide the delicate Purkinje neurons with a physiological environment close to that in vivo. We have optimized this system and are using it to examine the Atm-mediated DNA damage response (DDR) in the cerebellum, with special emphasis on Purkinje cells. Our results to date, which indicate special chromatin organization in Purkinje cells that affects certain pathways of the DDR, demonstrate the usefulness of cerebellar organotypic cultures for addressing the above questions.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Tzur-Gilat A,Ziv Y,Mittelman L,Barzilai A,Shiloh Ydoi
10.1016/j.mad.2013.04.001subject
Has Abstractpub_date
2013-10-01 00:00:00pages
496-505issue
10eissn
0047-6374issn
1872-6216pii
S0047-6374(13)00047-Xjournal_volume
134pub_type
杂志文章abstract::The synthesis of sulfated proteoglycans in late fetal (19th to 22nd day of intrauterine life), early postnatal, and adult liver tissue as well as in hepatocytes and their distribution in plasma membranes were studied. Overall proteoglycan production is enhanced two-fold in fetal as compared with adult liver tissue. In...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(85)90097-1
更新日期:1985-09-01 00:00:00
abstract::The present work explores the application of information theoretical measures, such as entropy and normalized mutual information, for research of biomarkers of aging. The use of information theory affords unique methodological advantages for the study of aging processes, as it allows evaluating non-linear relations be...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2017.01.003
更新日期:2017-04-01 00:00:00
abstract::Normal diploid Syrian hamster dermal mesenchymal cell strains, regardless of the age of the tissue of origin, exhibit in vitro cellular senescence. The frequency of spontaneous escape from senescence and conversion to a permanent cell line is less than 5% among replicate flasks. The overall pattern of senescence of ce...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(86)90032-1
更新日期:1986-04-01 00:00:00
abstract::The lifespan of the nematode, Caenorhabditis elegans, can be extended by mutations affecting components of the insulin-like growth factor (IGF) signaling cascade or by overexpression of SIR2, an NAD+-dependent protein deacetylase. The mammalian homologue of SIR2, Sirt1, has been shown to modulate the activity of FoxO,...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2005.04.006
更新日期:2005-10-01 00:00:00
abstract::Age related changes in some aspects of glutamate metabolism were followed in the brain of a short lived species of tropical murrel, Channa punctatus. Both ammonia and glutamine contents of brain increased with advancing age of the murrel. The glutamate dehydrogenase activity of brain increased during maturation phase ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(93)90139-i
更新日期:1993-05-01 00:00:00
abstract::Telomeres are supposed to play a role in cellular aging and might contribute to the genetic background of human aging and longevity. During the past few years telomere length has been measured in various human tissues. However, very little is known about the individual telomere loss in different tissues from the same ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(00)00173-1
更新日期:2000-11-15 00:00:00
abstract::The effect of aging on patterns of food intake and nutrient selection was investigated using a longitudinal study. Male (n = 10) and female (n = 10) Wistar-Lou rats from 4 to 28 months of age were repeatedly submitted to a macronutrient self-selection (S-S) regimen while controls were maintained under a standard chow ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(98)00013-x
更新日期:1998-07-15 00:00:00
abstract::The previous observation (Eur. J. Biochem., 82 (1978) 563--567) that age-dependent accumulation of lipid peroxides follows as a consequence of increased radical formation in mitochondria has prompted an examination of the response of a set of protective enzymes to the above situation. Levels of mitochondrial catalase ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(79)90050-2
更新日期:1979-10-01 00:00:00
abstract::Morphological studies on spontaneous systemic amyloidosis were conducted on 222 senescence-accelerated mice (SAM) (P) and on 150 mice in the senescence-resistant series (R). Among the pathologic findings, amyloidosis showed the highest incidence in both SAM (79.7%) and R (32.7%). Although an extensive deposition of am...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(82)90070-7
更新日期:1982-09-01 00:00:00
abstract::Two types of age-related cell surface changes could be demonstrated in human diploid fibroblasts with the two methods of the lectin-mediated red blood cell (RBC) adsorption assay: the fibroblast coating method (in which RBCs are adsorbed to lectin-coated fibroblasts) and the RBC coating method (in which lectin-coated ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(79)90004-6
更新日期:1979-11-01 00:00:00
abstract::The combined grafting of young bone marrow and newborn thymus performed in old mice was effective in restoring the impaired immune functions, but the same treatment performed in middle-aged adult mice had no effect on the life span of C3H/MTV female mice. Sequential multiple newborn thymus graftings starting at young ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(89)90067-5
更新日期:1989-07-01 00:00:00
abstract::We have examined the effects of aging on guinea pig biliary motility both in vitro and in vivo. The first experiment compared contractile tension of gallbladder strips from young adult (6-12 months old) and 3-year-old guinea pigs in vitro. Contraction of gallbladder strips from the young guinea pigs was twice as force...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(88)90127-3
更新日期:1988-12-01 00:00:00
abstract::Perceived age is an easily accessible biomarker of aging. Here, we studied its relation to DNA methylation age (DNAm age) as introduced in (Horvath, 2013) in 180 elderly Danish twins. We found perceived age and DNAm age to be associated with chronological age (P=0.04 resp. P=2.2e-10) when correcting for gender, but di...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2017.09.004
更新日期:2018-01-01 00:00:00
abstract::In this paper, we approach the problem of attempting to understand senescence by understanding the complexity and hierarchical structure of mammalian organisms. To do this, we make use of some concepts from abstract relational biology; in particular, graph theory. We subsequently utilize these concepts to develop the ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(84)90056-3
更新日期:1984-10-31 00:00:00
abstract::Ageing is the most complex phenotype currently known, since it becomes manifest in all organs and tissues, affects an organism's entire physiology, impacts function at all levels and increases susceptibility to all major chronic diseases. Insight into the molecular and cellular targets of the ageing process would offe...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/s0047-6374(02)00163-x
更新日期:2003-01-01 00:00:00
abstract::A method has been developed for the direct measurement of genetic variants in mammalian cells in culture which does not require cell division and is therefore suitable for ageing studies. Previous evidence suggests that these variants are mutations. The variant frequency was measured during the lifespan of populations...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(79)90074-5
更新日期:1979-04-01 00:00:00
abstract::Mutated huntingtin is expressed in nervous and non nervous system included lymphoblasts. Eneregetic metabolism is impaired in Huntington's disease (HD) and other neurodegenerative diseases. Human HD lymphoblasts have provided clear-cut data on mitochondnal disruption. Here we report morphological, morphometric and mem...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2005.09.010
更新日期:2006-02-01 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::A significant positive correlation between bone mineral density (BMD) and serum dehydroepiandrosterone sulfate (DHEA-S) was found in 120 postmenopausal women (51-99 years old) but no correlation was seen between BMD and serum estradiol. In subset analysis, strong positive correlation of serum DHEA-S and estrone with B...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(01)00394-3
更新日期:2002-04-30 00:00:00
abstract::An increase in natural (innate) immunity with age (through 65 weeks) of NBR rats to a syngeneic methylcholanthrene-induced fibrosarcoma (MCA) is described. This increase is characterized by the appearance of spontaneous tumor regressor animals and an increase in the incidence of tumor non-takes by rats 45 weeks of age...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(81)90129-9
更新日期:1981-09-01 00:00:00
abstract::Age-adjusted mortality rates for breast cancer (BC) in the United States from 1962 to 1987 were subjected to longitudinal Gompertzian analysis. Age-adjusted BC mortality rate distributions for women display two distinct Gompertzian slopes. Between age 15 and 40 years, age-adjusted BC mortality rate distributions inter...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(91)90125-j
更新日期:1991-10-01 00:00:00
abstract::Longevity regulatory genes include the Forkhead transcription factor FOXO, in addition to NAD-dependent histone deacetylase silent information regulator 2 (Sir2). The FOXO/DAF-16 family of transcription factors constitute an evolutionarily conserved subgroup within a larger family known as winged helix or Forkhead tra...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2004.09.021
更新日期:2005-01-01 00:00:00
abstract::Caenorhabiditis elegans males live longer than hermaphrodites when cultured individually. Since hermaphrodites contain a pair of X chromosomes (XX) and males are XO (there is no Y chromosome in C. elegans), we questioned whether chromosomal differences per se might impact life span. The use of mutations in the sex-det...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2007.06.001
更新日期:2007-07-01 00:00:00
abstract::The aim of this study was to investigate the effect of physical training on balance, strength, and general well-being in adult people with intellectual disability (ID). This study evaluated how physical training can effect physical and psychological change among 'older' adults with mild ID. Participants consisted of n...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2004.08.021
更新日期:2005-02-01 00:00:00
abstract::The B cell responsiveness mediated by T cells has been evaluated in 50 aged donors by using a Pokeweed mitogen (PWM)-driven differentiation system. Peripheral blood mononuclear cells (PBMC) from aged donors exhibited a lower plaque-forming cell (PFC) generation in comparison with young donors. Similar results were obt...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(87)90056-x
更新日期:1987-11-01 00:00:00
abstract::A morphometric investigation has been carried out on the synaptic junctions in the cerebellar glomeruli of young-adult rats chronically deprived of vitamin E for 10 months and control animals of the same age. The following parameters were evaluated: the average length of the synapses (L), the numerical (NV) as well as...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(84)90073-3
更新日期:1984-02-01 00:00:00
abstract::In this paper, we presented the results of analysis of experimental evidence for the decline of the human immune system functioning with age using mathematical model of immunosenescence. The most prominent changes in this system are related to the decline in the T-cellular immunity. These include the decline in the na...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(03)00019-8
更新日期:2003-04-01 00:00:00
abstract::We are interested in membrane phospholipid and triglyceride synthesis and turnover in aging cells. As a preliminary, short-term feasibility study we have used an established in vivo-in vitro technique to estimate the initial rates of [1-14C] palmitate (complexed to albumin) esterification to triglycerides and phosphol...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(82)90018-5
更新日期:1982-08-01 00:00:00
abstract::The effects of age on estrogen stimulated nuclear RNA polymerase II activity were studied in uteri of ovariectomized mature (6-8 months) and senescent (24 months) rats. Basal levels of RNA polymerase II activity were the same in both age groups. Following 17 beta-estradiol (E2) administration, RNA polymerase II activi...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(84)90136-2
更新日期:1984-04-01 00:00:00
abstract::T cell responses are altered in the aged in a manner usually interpreted as detrimental to host defences against infectious agents and possibly also against cancer. T cell dysregulation may be caused by any or a combination of stem cell deficits, compromised T cell differentiation, inefficient antigen processing and p...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/s0047-6374(01)00290-1
更新日期:2001-09-30 00:00:00