Abstract：
:Age-related loss of hearing and vision are two very common disabling conditions, but the underlying mechanisms are still poorly understood. Damage by reactive oxygen species and other reactive cellular metabolites, which in turn may damage macromolecules such as DNA, has been implicated in both processes. To investigate whether DNA damage can contribute to age-related hearing and vision loss, we investigated hearing and vision in Ercc1(δ/-) mutant mice, which are deficient in DNA repair of helix-distorting DNA lesions and interstrand DNA crosslinks. Ercc1(δ/-) mice showed a progressive, accelerated increase of hearing level thresholds over time, most likely arising from deteriorating cochlear function. Ercc1(δ/-) mutants also displayed a progressive decrease in contrast sensitivity followed by thinning of the outer nuclear layer of the eyeball. The strong parallels with normal ageing suggest that unrepaired DNA damage can induce age-related decline of the auditory and visual system.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Spoor M,Nagtegaal AP,Ridwan Y,Borgesius NZ,van Alphen B,van der Pluijm I,Hoeijmakers JH,Frens MA,Borst JGdoi
10.1016/j.mad.2011.12.003subject
Has Abstractpub_date
2012-02-01 00:00:00pages
59-67issue
2-3eissn
0047-6374issn
1872-6216pii
S0047-6374(12)00002-4journal_volume
133pub_type
杂志文章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：:It strikes me that among our relatively small community of gerontologists concerned with genetic approaches to our science, there is somewhat of a dichotomization. On the one hand, there are those of us, like myself, who tend to be dour 'complificationists'. Journalists talk to us, but are usually disappointed by the ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/s0047-6374(01)00335-9
更新日期：2002-01-01 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
abstract：:The decreased immune response associated with aging may, in part, reflect intrinsic age-related biochemical alterations in lymphocytes from older animals. We measured levels of lymphocyte adenosine triphosphate (ATP) and continuous [3H]thymidine incorporation in phytohemagglutinin-stimulated lymphocytes from young and...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(83)90098-2
更新日期：1983-09-01 00:00:00
abstract：:Age-specific mortality rates from stomach cancer (SC) in Japan from 1950 through 1993 were subjected to longitudinal Gompertzian analysis. Age-specific SC mortality rate distributions between ages 45 and 75 years were highly Gompertzian for each- and every year for both men and women. Between 1950 and 1993, age-adjust...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(95)01669-4
更新日期：1995-11-24 00:00:00
abstract：:Selenium (Se) is an essential trace mineral mediating its biological function primarily through selenoproteins. Accumulated lines of evidence indicate important roles of selenoproteins in the maintenance of optimal brain functions via redox regulation. Decreased expression of several selenoproteins is associated with ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2010.02.006
更新日期：2010-04-01 00:00:00
abstract：:The objective of the this study was to determine the cytokine profile of aging mice and to establish whether changes in cytokine production account for the fact that aging mice develop a milder disease than the young in response to induced experimental systemic lupus erythematosus (SLE). Cytokine secretion was evaluat...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(97)01891-5
更新日期：1997-06-01 00:00:00
abstract：:Aflatoxin B1(AFB1)-glutathione(GSH) conjugation is the major pathway for the detoxification of aflatoxin metabolites. This reaction is catalysed by GSH S-transferase (GST) and play a major role in modulation of AFB1 adduct formation to nuclear DNA. Changes recorded in hepatic GST activity during development of rats ca...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(00)00105-6
更新日期：2000-05-18 00:00:00
abstract：:Cyclic AMP levels and activities of adenylate cyclase and phosphodiesterase in the striatum were measured in 4, 12, 24 and 30 month-old rats. No age-related changes were observed either in cyclic AMP levels or basal adenylate cyclase activity. However, there was an age-related decline in dopamine sensitivity of adenyl...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(77)90006-9
更新日期：1977-01-01 00:00:00
abstract：:Relationships between nutrition and longevity are of growing interest. Here we analysed the influences of dietary restriction on the survival of Drosophila exposed to atmospheric oxygen or to chronic hypoxia. Dietary restriction was achieved by food dilution, by sucrose restriction or by yeast restriction. Sucrose and...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2007.05.008
更新日期：2007-05-01 00:00:00
abstract：:Developments in medicine have led to a significant increase in the average human lifespan. This increase in aging is most readily apparent in the case of HIV where antiretroviral therapy has shifted infection from a terminal to a chronic but manageable disease. Despite this advance, patients suffer from co-morbidities...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2018.07.008
更新日期：2018-10-01 00:00:00
abstract：:The proto-oncogene c-fos (the cellular homolog of v-fos, Finkel-Biskis-Jenkins (FBJ) murine osteogenic sarcoma virus) encodes a major component of the activator protein-1 (AP-1) transcription factor. Serum stimulation as well as oxidizing treatments induce transitory increases in c-fos mRNA abundance. The induction of...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(95)01689-9
更新日期：1996-03-29 00:00:00
abstract：:We have examined newly synthesized proteins in the young adult and in older populations of the nematode Caenorhabditis elegans using two-dimensional polyacrylamide gel electrophoresis (2D PAGE). A temperature-sensitive mutant strain, DH26, with a mean life span of about 15 days, under our conditions, was used to block...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(85)90118-6
更新日期：1985-05-31 00:00:00
abstract：:The age changes of neural control over the function of the thyroid, adrenal cortex and testicles were examined in adult (6 months) and old (28 months) male rats. In old age, there was a weakening of adrenergic control of thyroidogenesis, alpha-adrenergic and M-cholinergic control of glucocorticoid function of the adre...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(90)90165-c
更新日期：1990-01-01 00:00:00
abstract：:Concanavalin A (Con A)-mediated red blood cell (RBC) adsorption with the RBC coating method (in which Con A-coated RBC's are adsorbed to fibroblasts) was greatly increased by glutaraldehyde fixation of RBCs before Con A-coating and decreased by the fixation of fibroblasts. On the other hand, RBC adsorption with the fi...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(79)90003-4
更新日期：1979-11-01 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
abstract：:Elderly people are at risk from an increased incidence of infections. Therefore we have studied the correlation between the production of several immunological parameters such as interferon-gamma (IFN-gamma), interferon-alpha-2 (IFN-alpha-2), interleukin-2 (IL-2), soluble interleukin-2 receptors (sIL-2R) and interleuk...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(93)90066-z
更新日期：1993-08-01 00:00:00
abstract：:In the present study we have investigated the prevalence of organ-specific and non organ-specific autoantibodies in 26 healthy centenarians (6 men, 20 women; age range 101-106 years), using as controls 54 healthy old (33 men and 21 women, age range 71-93) and 56 young subjects (29 men and 27 women, age range 26-60). W...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(96)01845-3
更新日期：1997-03-01 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：:Hepatocyte morphology of the three zones of the liver lobule was evaluated by stereological analysis in 3-month-old and 35-month-old virgin female WAG/Rij rats. In the old rats, the volume of the nucleus and cytoplasm, and volume densities of smooth endoplasmic reticulum and lysosomes were increased in all areas of th...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(80)90054-8
更新日期：1980-06-01 00:00:00
abstract：:Semantic distinctions between "normal" aging, "pathological" aging (or age-related disease) and "premature" aging (otherwise known as segmental progeria) potentially confound important insights into the nature of each of the complex processes. Here we review a recent, unexpected discovery: the presence of longevity-as...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2006.11.011
更新日期：2007-01-01 00:00:00
abstract：:The release of cytokines is of crucial importance in the regulation of the type and magnitude of the immune response in the elderly. A number of studies have shown different levels of cytokine production in the elderly. In the present study, a range of polymorphisms were chosen within the genes of cytokines (IL-2, IL-...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(02)00132-x
更新日期：2003-02-01 00:00:00
abstract：:Neurons that degenerate in the brains of persons with Alzheimer's disease accumulate mitochondrial amyloid precursor protein (APP), which is thought to negatively affect mitochondrial function and cellular homeostasis. Because proteins that enter mitochondria require assistance from chaperone proteins, we hypothesized...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2009.07.002
更新日期：2009-09-01 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：: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：:Highly purified DNA has been prepared from human muscle tissue and treated with three different single-strand specific desoxyribonucleases. The molecular weight of treated individual DNA molecules was determined by length measurements. Average DNA molecular weights and their standard deviations were correlated to the ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(83)90089-1
更新日期：1983-07-01 00:00:00
abstract：:The purpose of this research is to determine possible causes and mechanisms involved in the age-associated decline in mitochondrial activity. We have focused on cytochrome c oxidase because it is comprised of both nuclear and mitochondrial-encoded subunits and may provide some insight into the coordination of the two ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(98)00043-8
更新日期：1998-06-15 00:00:00
abstract：:To determine the effects of prolonged hypoxia and hypoxia-reoxygenation in senescent blood vessels, isolated aortic rings from 4- and 24-month-old (mo) Wistar rats were submitted to prolonged hypoxia (50 min) or hypoxia/reoxygenation (20 min/30 min) and contractile function recorded. Phenylephrine-induced contraction ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(01)00327-x
更新日期：2002-02-01 00:00:00
abstract：:This review addresses a novel facet of human T cell biology that constitutes a fundamental problem for long-term maintenance of immunological memory against viruses. The finite proliferative capacity of human T lymphocytes is sufficiently great to accommodate the waves of clonal expansion associated with primary and e...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/s0047-6374(00)00207-4
更新日期：2000-12-20 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
