Abstract：
:A major cause of ageing is thought to be the accumulation of damage to macromolecules. Accumulation to DNA damage in cells therefore presupposes that aged cells are unable to repair this damage. We have used the in vitro model of cellular ageing to test the idea that senescent cells are deficient in some aspect of DNA repair. Using the alkaline single cell gel electrophoresis assay (comet assay), we have determined the responses of young and senescent human dermal fibroblasts to DNA damage caused by exposure to UVC light. At low doses of UVC, senescent cells generate smaller comets than young cells whilst at medium doses the situation is reversed. At high doses, young and senescent cells respond similarly to one another. Time course experiments revealing repair of DNA damage show that senescent cells generate larger comets than young cells at early stages of repair suggesting that either senescent cells bear more damage per genome than do young cells or that senescent cells are more efficient at excising bulky adducts from DNA. Cells maintained in low levels of serum irrespective of age are less able to repair DNA damage compared with cells maintained in high levels of serum, and furthermore young and senescent cells maintained in high levels of serum are equally able to repair DNA damage. Our data, therefore, reveal both age-dependent and age-independent responses to UV-induced DNA damage. Use of the comet assay highlights the heterogeneity of cellular responses to genotoxic stress.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Al-Baker EA,Oshin M,Hutchison CJ,Kill IRdoi
10.1016/j.mad.2004.12.002subject
Has Abstractpub_date
2005-06-01 00:00:00pages
664-72issue
6-7eissn
0047-6374issn
1872-6216pii
S0047-6374(04)00338-0journal_volume
126pub_type
杂志文章abstract：:Lipofuscin accumulation in cultured rat myocardial cells is considered an index of intra-lysosomal oxidative reactions and was registered by autofluorescence measurements. Lipofuscinogenesis in secondary lysosomes is thought to be a consequence of Fenton reactions, and is much enhanced by oxidative stress obtained by ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(94)01569-8
更新日期：1995-06-09 00:00:00
abstract：:During senescence, autofluorescent lysosomal storage bodies known as lipofusin or age pigment accumulate in many post-mitotic types of cells. Among these cell types is the retinal pigment epithelium (RPE) of the mammalian eye. The mechanisms of lipofuscin formation and accumulation have been studied more extensively i...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2004.11.004
更新日期：2005-04-01 00:00:00
abstract：:The antigen-specific antibody secretion in vitro after immunisation with the primary T-cell dependent antigen Helix pomatia Haemocyanin (HPH) was investigated in both young and elderly individuals, who all met the health admission criteria for immunogerontological studies as detailed in the SENIEUR protocol. In additi...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(92)90069-p
更新日期：1992-01-01 00:00:00
abstract：:A 3'-->5' exonuclease found in rat liver excises mispaired nucleotides at the 3'-hydroxyl end of primer chains such as poly dA-d(T9-C). Consequently, the priming activity of the chain from which the mispaired base was cut is greatly increased during DNA synthesis. These results suggest that the 3'-->5' exonuclease act...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(98)00083-9
更新日期：1998-09-15 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 activities of the low-Km and high-Km forms of cyclic AMP phosphodiesterase (PDE) were determined in extracts prepared from epididymis and prostate taken from adult (10-12 months) and from aged (32-35 months) rats. The maximum velocity V of low-Km PDE in the epididymis of normal adult rats (approx. 300 pmoles/min p...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(88)90097-8
更新日期：1988-04-01 00:00:00
abstract：:The effects of age and nutritional conditions on accumulation of autofluorescent granules in various organs and tissues of male Sprague-Dawley rats were compared morphometrically. The relative intensity of the specific fluorescence of these autofluorescent granules was similar in all tissues and cells examined. In alm...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(88)90033-4
更新日期：1988-06-01 00:00:00
abstract：:Healthy elderly (80+/-5 years) with different nutritional status were compared to young healthy adults (25+/-5 years) to quantify the relative influences of aging and nutrition on immune response. Aged persons, without alteration of their nutritional status, had lower CD3+, CD8+, and CD45RA+ as well as higher CD2+CD3-...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(98)00047-5
更新日期：1998-08-01 00:00:00
abstract：:The risk for developing colorectal cancer increases exponentially with age. We demonstrate that spontaneous loss of folate in the colon results in DNA damage accumulation and aberrant DNA damage responses that may contribute to the increased genomic instability and cancer risk in colon. We find greater than 2-fold cha...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2012.01.003
更新日期：2012-02-01 00:00:00
abstract：:Expression of dystrophin and the dystrophin-related protein utrophin has been studied in the human fetal brain both in vivo and in vitro. Results showed that both these proteins were developmentally regulated, even if their expression followed a different pattern. Utrophin was found since very early stages of developm...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(01)00360-8
更新日期：2002-03-15 00:00:00
abstract：:The endothelin-1 (ET-1) concentrations were measured by RIA in the media of confluent monolayer cultures of rat articular chondrocyte (RAC) exposed to fetal calf serum (FCS) and several growth factors and cytokines. The cells were obtained from 1- and 18-month-old rats. First passage cells were starved in Dulbecco's m...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(99)00117-7
更新日期：2000-02-22 00:00:00
abstract：:The age-dependent drop in mixed lymphocyte reactivity and responsiveness to concanavalin A of lymph node and spleen cells of C57Bl/6J female mice were studied. The relative decrease in mixed lymphocyte reactivity was shown to be the same whether mounted against H-2 or Mls incompatibile stimulator cells. The time of pe...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(79)90118-0
更新日期：1979-01-01 00:00:00
abstract：:Overproduction of oxidants and free radicals in ageing tissues induces nitro-oxidative stress, which has recently been implicated in the pathogenesis of cardiovascular dysfunction associated with ageing. Peroxynitrite, a strong cytotoxic oxidant damages proteins and DNA and activates several pathways causing tissue in...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2006.09.005
更新日期：2007-02-01 00:00:00
abstract：:Interfibrillar mitochondria (IFM) of the heart in aged Fischer 344 rats show a biochemical defect which might be reflected in their morphology. We examined by high resolution scanning electron microscopy over 5500 mitochondria to determine if a concomitant structural alteration existed. This methodology provides a mea...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2006.09.002
更新日期：2006-12-01 00:00:00
abstract：:The purpose of the present study was to investigate the effect of aging on silica-induced lung toxicity. In young animals silica induced a significant increase in bronchoalveolar lavage tumor necrosis factor-alpha (TNF), lactate dehydrogenase as well as in cell numbers, which correlate with increased collagen depositi...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2003.11.002
更新日期：2004-02-01 00:00:00
abstract：:This is the first in a series of articles in which we intend to critically review some of the currently used models in gerontology research and evaluate their contribution to advancing our understanding of the phenomenon of senescence. The major theories of aging are considered. We discuss what makes a model useful in...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/s0047-6374(00)00141-x
更新日期：2000-08-15 00:00:00
abstract：:Mitochondrial DNA (mtDNA) was isolated from liver mitochondria of rats between 2 and 24 months of age. The mtDNA was purified by cesium chloride--ethidium bromide isopycnic density gradient centrifugation. In the gradients, in addition to the two expected bands of ethidium--DNA complex, there was observed a third, mor...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(82)90090-2
更新日期：1982-11-01 00:00:00
abstract：:MARK-AGE aims at the identification of biomarkers of human aging capable of discriminating between the chronological age and the effective functional status of the organism. To achieve this, given the structure of the collected data, a proper statistical analysis has to be performed, as the structure of the data are n...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2015.07.001
更新日期：2015-11-01 00:00:00
abstract：:The present study examined the effect of repeated vaccination and of dehydroepiandrosterone (DHEA) treatment on the immune response to influenza vaccine in elderly subjects. Seventy-one elderly volunteers, aged 61-89 years, enrolled in a prospective randomized, double-blind study to receive either DHEA (50 mg qd p.o. ...
journal_title：Mechanisms of ageing and development
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/s0047-6374(98)00017-7
更新日期：1998-05-15 00:00:00
abstract：:In an attempt to understand the molecular mechanisms of age-dependent degenerative alteration in human periodontal tissues, we examined mRNA level and DNA methylation of collagen alpha1(I) gene. Using healthy periodontal ligament tissues from humans aged 9-76 years, we found that the collagen alpha1(I) mRNA level decr...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(99)00041-x
更新日期：1999-10-01 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：: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 current increase in life expectancy observed in industrialized societies underscores the need to achieve a better understanding of the aging process that could help the development of effective strategies to achieve healthy aging. This will require not only identifying genes involved in the aging process, but also...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2006.12.003
更新日期：2007-03-01 00:00:00
abstract：:In this paper, I attempt to address the problem of how to model the survival curve in the early lifespan years; the neonatal years. I present a general model for a two group population in which the first group represents early stage failure and the second group represents the classical Gompertzian failure. After calcu...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(86)90026-6
更新日期：1986-01-01 00:00:00
abstract：:Oxidative energy metabolism in mouse liver mitochondria was examined during weaning using different substrates. During the post-natal development, from suckling to weanling stage, the respiration rates showed a temporary decrease. These altered levels recovered in the adults. Respiration rates with the three substrate...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(90)90060-s
更新日期：1990-05-30 00:00:00
abstract：:The present study examined the effect of a 40% reduction in caloric intake (CR) versus ad libitum (AL) feeding on retinal aging. CR- and AL-fed Brown Norway (BN) rats were obtained at 12, 24 and 30 months of age from the National Center for Toxicological Research (NCTR). Age-dependent declines in outer nuclear layer (...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(00)00096-8
更新日期：2000-03-13 00:00:00
abstract：:In this article we review the abnormalities in immune function which have been described in relation to ageing. It is suggested that thymic involution may not be the only underlying cause. Many similar changes can be induced by the endotoxins from the cell walls of Gram-negative bacteria. The colon is a large reposito...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/0047-6374(84)90091-5
更新日期：1984-08-01 00:00:00
abstract：:Age-specific incidence rates for cancers of the female breast, ovary, corpus uteri, testis, prostate and male and female cancers of the stomach, colon, rectum, lung, and male and female Hodgkin's disease in 51 worldwide populations in the 1990 era were obtained from a published source. For each cancer in each populati...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(02)00113-6
更新日期：2003-03-01 00:00:00
abstract：:Researchers and clinicians interested in human diseases of DNA repair deficiency and premature aging gathered at the National Conference Center in Lansdowne, Virginia on 5-8 September 2006 to attend a workshop co-organized by Vilhelm Bohr (National Institute of Aging) and Kenneth Kraemer (National Cancer Institute). A...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2006.11.028
更新日期：2007-02-01 00:00:00
abstract：:Dietary factors have a profound effect on many aspects of health including ageing and do so, at least partly, through interactions with the genome which result in altered gene expression. The application of high throughput genomics technologies in nutritional research (nutrigenomics) offers a new approach to understan...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2006.01.018
更新日期：2006-06-01 00:00:00
