Abstract:
:Nearly 40 years ago it was proposed that accumulation of mutations or increased levels of DNA damage might contribute to aging processes. Despite several correlative studies in this area, the answer as to whether genomic integrity contributes to aging has remained illusive. More recently it has been hypothesized that decreased mitochondrial DNA integrity plays a role in aging. To begin to test these hypotheses more directly, we are developing transgenic mouse and cell culture model systems. For example, transgenic mice overexpressing the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) have been made and have a reduced spontaneous frequency of hepatocellular carcinoma. A lifespan study using the MGMT transgenic mice is in progress in an effort to determine whether cancer impacts on the median or maximal lifespan of a species. Second, a quantitative PCR technique is being used to measure mitochondrial DNA damage in mitotic and post-mitotic cells to determine if the level of damage and/or repair is different based on mitotic status. Finally, mice deficient in metallothionein-I and -II are being used in an effort to determine if the subcellular distribution of metals impact on oxidative damage with increased age.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Walter CA,Grabowski DT,Street KA,Conrad CC,Richardson Adoi
10.1016/s0047-6374(97)00108-5subject
Has Abstractpub_date
1997-12-01 00:00:00pages
203-22issue
3eissn
0047-6374issn
1872-6216pii
S0047637497001085journal_volume
98pub_type
杂志文章,评审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
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::Survival characteristics of seven different populations of the mollusc Lymnaea stagnalis were studied under constant culture conditions. On the basis of these characteristics four populations were considered as healthy and three as infected. In the healthy populations senescence started at an age of about 200 days, 50...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(88)90052-8
更新日期:1988-03-01 00:00:00
abstract::Several alternative mortality models fit Swedish old-age mortality data equally well. The models build on two different concepts of the heterogeneity of individuals in a population. The first concept concerns fixed, genetic differences among individuals in their risk of death. The second concept involves acquired susc...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(94)90094-9
更新日期:1994-05-01 00:00:00
abstract::T cells in vivo have been shown to accumulate DNA damage with age. To investigate the effects of DNA damage on T cell biology we have utilised an in vitro human CD4+ T cell clone model. Levels and types of DNA damage were determined in 11 independent T cell clones as a function of their in vitro lifespan. Increased le...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(01)00254-8
更新日期:2001-08-01 00:00:00
abstract::Previous studies have suggested a possible relationship between the ubiquitin-proteasome pathway and some pathological manifestations of Alzheimer's disease (AD). This study investigated the possibility that the Abeta peptides interact with the ubiquitin-proteasome pathway inside neuronal cells. The ubiquitin-proteaso...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2005.07.006
更新日期:2005-12-01 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::Pancreatic islet B cells from Sprague-Dawley and Fisher 344 rats aged 3-27 months were separated from A and D cells by centrifugation over a linear percoll density gradient, and incubated in vitro with various concentrations of glucose and somatostatin. Elevation of glucose concentration in the incubation medium from ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(86)90022-9
更新日期:1986-01-01 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 paper of Kitani cited in the title has raised an apparent contradiction regarding the validity of certain aspects of the membrane hypothesis of aging (MHA). He collected data showing that a number of detoxifying liver enzyme activities, although decline with age in male Fischer 344 rats, remain at an unchanged lev...
journal_title:Mechanisms of ageing and development
pub_type: 评论,杂志文章
doi:10.1016/s0047-6374(01)00237-8
更新日期:2001-06-01 00:00:00
abstract::To investigate age-related changes in gene expression in WI-38 cells, we isolated RNA from young and senescent, quiescent cultures and made subtracted cDNA libraries. Density-arrested cells were incubated in serum-free MCDB-104 for 3 days. RNA was then isolated and subtracted cDNA libraries were made in the phagemid v...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(92)90039-g
更新日期:1992-09-01 00:00:00
abstract::The age-related changes in the distribution of enkephalin-immunoreactive (ENK-IR) nerve fibers in relation to the principal neurons were studied in 23 human sympathetic ganglia from patients aged between 22 and 98 years. There were no age-related changes in the diameter of nerve cells and the packing density of the ne...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(88)90086-3
更新日期:1988-08-01 00:00:00
abstract::The present study was designed to assess whether treatment with the monoamine oxidase-B (MAO-B) inhibitor L-deprenyl, which has been documented to increase both mean and maximum survival in aged rats as well as sexual performance and cognitive function, has any effect on the age-related microanatomical changes occurri...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(94)90060-4
更新日期:1994-02-01 00:00:00
abstract::Lymphatic lipid transport in the intestine of adult and ageing rats was compared. Adult (8-10 months old) and old (24-26 months old) male Wistar rats were cannulated into the mesenteric lymph under ethrane anesthesia. On the following day, lipid emulsion containing 35.4 mg/h of olive oil was infused intraduodenally fo...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(99)00110-4
更新日期:2000-02-15 00:00:00
abstract::We have previously reported that two or more different subpopulations of bone marrow stem cells exist in mice as determined by cycling status of day-8 and day-14 CFU-S in long term bromodeoxyuridine (BrdU) infusion studies. In the present report, comparisons between cycling of stem cell subpopulations in old and young...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(89)90069-9
更新日期:1989-07-01 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::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 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::Aging is characterized by a progressive loss of several physiological functions that can cause various age-related disorders. Several factors have been identified as causes of aging to elucidate the decline in functions. Various aspects of physiological deterioration are controlled by the hypothalamus, a critical brai...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/j.mad.2018.04.008
更新日期:2019-01-01 00:00:00
abstract::Age-related and ambient temperature-related changes in motor activity, body temperature, body weight (b.w.), and food consumption were studied in the long-lived Peromyscus leucopus mouse at environmental temperatures of 29 and 21 degrees C. Major changes in physiological performance were observed between the young (6 ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(96)01834-9
更新日期:1997-04-01 00:00:00
abstract::The functional deterioration of an organism with age causes the major problem of maintaining the quality of life at old age. Degenerative changes in the organism may to some extent reflect alterations that can be observed in cells during in vitro replicative senescence. At the cellular level, the receptor-mediated end...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/s0047-6374(02)00029-5
更新日期:2002-04-30 00:00:00
abstract::Accumulation of oxidative DNA damage in the human brain has been implicated in etiologies of post-traumatic and age-associated declines in neuronal function. In neurons, because of high metabolic rates and prolonged life span, exposure to free radicals is intense and risk for accumulation of damaged DNA is amplified. ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/j.mad.2008.02.001
更新日期:2008-07-01 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::This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of Marie-Ange Teste, Isabelle Léger-Silvestre, Jean M François and Jean-Luc Parrou. Marjorie Petitjean could not b...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,收录出版
doi:10.1016/j.mad.2016.07.011
更新日期:2017-01-01 00:00:00
abstract::Menopause is characterized by the depletion of estrogen that has been proposed to cause oxidative stress. Circadian rhythm is an internal biological clock that controls physiological processes. It was analyzed the gene expression in peripheral blood mononuclear cells and the lipids and glucose levels in plasma of a su...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.mad.2017.04.002
更新日期:2017-06-01 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::Previous studies from this laboratory have documented a progressive age-related decline in trophic hormone (or second messenger cAMP) stimulated corticosterone production in isolated adrenocortical cells. In the current study, we examined the possibility that the aging process exerts this effect by interfering with an...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(94)90043-4
更新日期:1994-11-25 00:00:00
abstract::Ascorbic acid content decreased with age in livers of male rats but not in those of female rats. The influence of aging on the regeneration of ascorbic acid from dehydroascorbic acid was investigated as a possible cause of declining ascorbate concentrations. The results demonstrate that hepatic NADPH-dehydroascorbic a...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(96)01784-8
更新日期:1996-11-13 00:00:00
abstract::Age-related changes in blood-brain barrier permeability to macromolecules were investigated during electrically induced seizures. Evans-blue was used as the barrier tracer. There was no change in the permeability of the blood brain barrier associated with aging in the rats. However, the extravasation of Evans-blue alb...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(90)90097-y
更新日期:1990-02-01 00:00:00
abstract::In an interspecies comparison of seven primate species, the expression of the erbB proto oncogene was found to be higher in fibroblasts derived from three relatively long-lived species, the human, gorilla, and chimpanzee than in cells from the orangutan, pygmy chimpanzee, squirrel monkey, or red-bellied tamarin. No si...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(87)90007-8
更新日期:1987-07-01 00:00:00