Abstract:
:The tumor suppressors p16(INK4a) and p53 have been implicated as contributors to age-associated stem cell decline. Key functions of p53 are the induction of cell cycle arrest, senescence, or apoptosis in response to DNA damage. Here, we examine senescence, apoptosis, and DNA damage responses in a mouse accelerated aging model that exhibits increased p53 activity, the p53(+/m) mouse. Aged tissues of p53(+/m) mice display higher percentages of senescent cells (as determined by senescence-associated beta-galactosidase staining and p16(INK4a) and p21 accumulation) compared to aged tissues from p53(+/+) mice. Surprisingly, despite having enhanced p53 activity, p53(+/m) lymphoid tissues exhibit reduced apoptotic activity in response to ionizing radiation compared to p53(+/+) tissues. Ionizing radiation treatment of p53(+/m) tissues also induces higher and prolonged levels of senescence markers p16(INK4a) and p21, suggesting that in p53(+/m) tissues the p53 stress response is enhanced and is shifted away from apoptosis toward senescence. One potential mechanism for accelerated aging in the p53(+/m) mouse is a failure to remove damaged or dysfunctional cells (including stem and progenitor cells) through apoptosis. The increased accumulation of dysfunctional and senescent cells may contribute to reduced tissue regeneration, tissue atrophy, and some of the accelerated aging phenotypes in p53(+/m) mice.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Hinkal GW,Gatza CE,Parikh N,Donehower LAdoi
10.1016/j.mad.2009.01.001subject
Has Abstractpub_date
2009-04-01 00:00:00pages
262-71issue
4eissn
0047-6374issn
1872-6216pii
S0047-6374(09)00004-9journal_volume
130pub_type
杂志文章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::Hepatocytes isolated from young (1 month) rats were as sensitive to the cytotoxic effects of erythromycin estolate and chlorpromazine as were liver cells obtained from older (3, 10 and 24 months) rats. The hepatocytes from the 24-month-old rats released aspartate transaminase more slowly than did parenchymal cells iso...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(80)90022-6
更新日期:1980-01-01 00:00:00
abstract::On a DNA basis, there is higher concentration of polysomes in the brain of newborn than in the brain of adult mice, but there is no maturation-dependent decrease in tRNA content during postnatal development. The amino acid incorporating activity of cell-free systems with polysomes or mitochondria from newborn brain ex...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(79)90040-x
更新日期:1979-05-01 00:00:00
abstract::To test the validity of estimating age-related changes in rat liver nuclear RNA synthesis by following the incorporation of radioactive nucleotides into an acid-insoluble product, age-related changes in endogenous nucleotide concentration were investigated. Both the total nucleotide and the nucleoside monophosphate (N...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(80)90087-1
更新日期:1980-02-01 00:00:00
abstract::Aging is a biological process associated with impairment of mitochondrial bioenergetic function, increased oxidative stress, attenuated ability to respond to stresses and increased risk in contracting age-associated diseases. When mitochondria are subjected to oxidative stress, accompanied by calcium overload and ATP ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2012.12.006
更新日期:2013-01-01 00:00:00
abstract::The age-related changes of the ciliary muscle of human eyes (33-87 years) were studied on histological meridional sections. Eighty-five melanoma eyes and 10 eyes of normal donors were investigated. The total area and the length of the muscle, the area of the three main portions and the distance of the inner apex of th...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(92)90057-k
更新日期:1992-02-01 00:00:00
abstract::We have developed a novel method to examine the translational fidelity of mammalian ribosomes in vitro, where protamine mRNA was used as a template. This method enabled us to determine frequency of misrecognition of purine bases at the second position of arginine codons (AGR/AAR) in the mRNA. Using this method the fid...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(83)90002-7
更新日期:1983-05-01 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::In predicting the degree of brain atrophy as measured by CT, the AGP score and a few clinical variables were of some remarkable value. Especially the variables related to memory disorders and lack of insight are easily and reliably assessed during the course of the examination. In comparison to other more widely used ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(80)90017-2
更新日期:1980-11-01 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::The microtubule-associated protein tau, and the cytoplasmic protein ubiquitin, are constituents of pathological neurofibrillary tangles found in Alzheimer's disease. In order to see if there is any physiological relationship between these proteins in a functioning human system, human neuroblastoma (LAN-5) cells were g...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(91)90002-h
更新日期:1991-11-15 00:00:00
abstract::To further explore whether immune function and acute phase response are altered during ageing, the response to a mild inflammatory stress (DT-Polio-Typhim vaccination) was studied in elderly and young subjects. Cytokine production (IFN-gamma, TNF-alpha, IL-6, IL-10) by whole blood cultures, circulating cytokines and a...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2005.03.008
更新日期:2005-08-01 00:00:00
abstract::In a longitudinal design in which each animal was examined repeatedly throughout its life, we used flow cytometry to determine the numbers or proportions of a variety of T lymphocyte subsets in the peripheral blood of mice aged 8-20 months. Half of the 128 mice were given a low calorie diet which is known to extend li...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(97)01893-9
更新日期:1997-06-01 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::The lipid peroxidation and activities of main enzymes involved in the peroxide metabolism were measured at resting conditions and after completion of a 2-month treatment with H2O2. At the start of the experiments 1- and 3-month-old female BALB/c mice received either a high dose of H2O2 (0.5% H2O2 in drinking water; in...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(84)90030-7
更新日期:1984-12-01 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::While deviations from the optimal phenotype are deleterious, increased variation can prevent population extinction under severe stresses. Cell division asymmetry is an important source of microbial phenotypic heterogeneity. A consecutive set of asymmetric divisions can cause the gradual accumulation of deleterious fac...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/j.mad.2018.09.001
更新日期:2018-12-01 00:00:00
abstract::In this study, we proposed a hypothesis that chromatin of mouse hepatocytes exhibits age-related reduction of fractal dimension. This hypothesis was based on previously published works demonstrating that complexity of biological systems such as tissues, decreases during the process of physiological aging. Liver tissue...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2016.07.002
更新日期:2016-07-01 00:00:00
abstract::Changes in the T cell pool caused by CMV infection have been proposed to contribute to immunosenescence, but it has been postulated that CMV can also have some beneficial effects in young individuals improving the immune response to other pathogens. T cells expressing CD56 (NKT-like cells) are cytotoxic effector cells...
journal_title:Mechanisms of ageing and development
pub_type: 临床试验,杂志文章
doi:10.1016/j.mad.2015.12.003
更新日期:2016-09-01 00:00:00
abstract::The aim of the present study was to measure protein synthesis in regenerating liver and to evaluate the impact of malnutrition in young and old rats. Two groups of male Wistar rats were used: young rats (4 months old) and old rats (18 months old). The rats were allocated to malnutrition or ordinary food intake for 1 w...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(96)01779-4
更新日期:1996-10-04 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
abstract::Anucleate minicells produced by a mutated strain of Escherichia coli remain metabolically active for up to 48 h at 37 degrees C. Minicells of increasing age have been infected with the coliphage T7. Infection results in the onset of transcription and translation producing T7 encoded polypeptides. Quantitative and qual...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(84)90045-9
更新日期:1984-10-15 00:00:00
abstract::It has been shown that enhanced levels of p53 activity contribute to reduced cancer susceptibility in mice, however longevity is compromised due to the onset of an early-ageing phenotype. The effects of enhanced levels of p53 in these in mice could therefore have implications for human premature ageing disorders. We e...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(03)00007-1
更新日期:2003-05-01 00:00:00
abstract::The responses of the left and right ventricles (LV and RV) to physical conditioning in cold (25 degrees C) and thermoneutral temperatures (35 degrees C), with special reference to lactate dehydrogenase (LDH) and its isoenzyme profile, were studied in the 2-month (young)- and 12-month (middle-aged)-old rats. Moderate h...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(99)00004-4
更新日期:1999-04-01 00:00:00
abstract::Understanding mechanisms underlying longevity, and endeavor towards the specific goals of alleviating frailty in old age, require a comprehensive approach that considers the various theoretical and experimental approaches, as well as compiling the data on humans. This logistic has underlined the program of the confere...
journal_title:Mechanisms of ageing and development
pub_type: 社论,评审
doi:10.1016/j.mad.2004.08.013
更新日期:2005-02-01 00:00:00
abstract::Elevated reactive oxygen species (ROS) levels have been observed in mammals during aging, implying an important role of ROS in the aging process. Most bird species are known to live longer and to contain lower ROS levels than mammals of the same body weight. The influence of ROS on the aging process of birds has been ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2009.11.005
更新日期:2010-01-01 00:00:00
abstract::Components of the calmodulin system (i.e., calmodulin levels and activities of the following calmodulin-dependent enzymes: Ca2+ + Mg2+-ATPase, adenylate and guanylate cyclases, cyclic AMP and cyclic GMP phosphodiesterases, and Ca2+-dependent protein kinase were studied in the following brain regions from immature (25-...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(86)90018-7
更新日期:1986-10-01 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::Our previous results indicated that glutathione (GSH) and/or cysteine (Cys) deficiency occurs in many aging tissues and also after acetaminophen (APAP) administration. The aim of this study was to investigate whether GSH monoethyl ester (GSH-OEt) can correct these deficiencies. Mice of different ages (3-31 months) thr...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(00)00214-1
更新日期:2000-12-01 00:00:00
abstract::The effects of long-term caloric restriction on the hepatic phase II drug metabolizing enzymes were investigated in the male Fischer 344 rat. Rats that had been restricted to 60% of their pair-fed control consumption from 14 weeks post-partum exhibited altered conjugating enzyme activities at 22 months. Caloric restri...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/0047-6374(89)90047-x
更新日期:1989-05-01 00:00:00