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 changes in the expression of folate-absorption and folate retention genes within the colonocyte, demonstrating that with age the colon is able to induce expression of appropriate genes in response to limiting folate status. However, we also find that aging results in spontaneous accumulation of uracil in colon DNA, indicating that folate status is not fully restored by the increase in folate absorption. Expression of uracil-excising enzymes (Ung and Smug) are induced in response to uracil accumulation, and with age we see an approximate 3-fold increase in the level of expression that is matched by a corresponding increase in DNA polymerase β expression. In further evaluating the DNA damage response, we investigated p53 localization and function and find abundant p53 levels, with p53 sequestered almost entirely in the cytoplasm. To determine whether cytoplasmic localization might impact p53 transactivation function, we conducted an unbiased screen of p53-target genes and found that age substantially alters expression of p53-target genes.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Simon KW,Ma H,Dombkowski AA,Cabelof DCdoi
10.1016/j.mad.2012.01.003subject
Has Abstractpub_date
2012-02-01 00:00:00pages
75-82issue
2-3eissn
0047-6374issn
1872-6216pii
S0047-6374(12)00005-Xjournal_volume
133pub_type
杂志文章abstract：:DNA damage and mutations have been implicated as key causal events in the biological process of aging. In this context, it has been hypothesized that the complex of genome maintenance systems acts as a longevity assurance system by signaling and repairing damage or removing cells that are beyond repair. In the past, v...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2008.02.009
更新日期：2008-07-01 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：:At least five different transgenic approaches have been applied to the study of Drosophila aging. There are two single component systems: transgenes with native (normal) promoters and transgenes with heterologous promoters; as well as three binary systems: 'GAL4/UAS', 'FLP-out' and 'tet-on'. These approaches vary in a...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/s0047-6374(00)00152-4
更新日期：2000-09-01 00:00:00
abstract：:A progressive decrease of dopamine and related enzyme activities and a decline in the dopaminergic receptor functions in the striatum and limbic system controlling behavior have been observed in senescent brain. These changes provide a neurochemical basis for some behavioral and mental disturbances of the aged and sug...
journal_title：Mechanisms of ageing and development
pub_type： 临床试验,杂志文章
doi：10.1016/0047-6374(80)90125-6
更新日期：1980-09-01 00:00:00
abstract：:The survival rate was measured of differently aged rabbit erythrocytes that had been taken from young and old animals, tagged with 51Cr and injected into young and old animals. The survival rate of the donor erythrocytes depends mostly on the age of the recipient animals. The life span of the injected cells found in o...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(81)90063-4
更新日期：1981-11-01 00:00:00
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 ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/s0047-6374(97)00108-5
更新日期：1997-12-01 00:00:00
abstract：:BCL-2 functions as a death repressor molecule in an evolutionary conserved cell death pathway. Inactivation of bcl-2 in mice results in pleiotropic effects including postnatal growth retardation, massive apoptosis in lymphoid tissues, polycystic kidney disease (PKD) and shortened lifespan. To evaluate the influence of...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2006.02.009
更新日期：2006-07-01 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：:The human premature aging protein Werner (WRN), deficient in Werner syndrome (WS), is localized mainly to the nucleolus in many cell types. DNA damage or replication arrest causes WRN to redistribute from the nucleolus to the nucleoplasm into discrete foci. In this study, we have investigated DNA damage specific cellu...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2005.06.004
更新日期：2005-11-01 00:00:00
abstract：:The potential gain in life expectancy which could result from the complete elimination of mortality from cancer in the U.S. would not exceed 3 years if one were to consider cancer independently of other causes of death. In this paper, we review evidence of trade-offs between cancer and aging as well as between cancer ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2008.03.006
更新日期：2009-01-01 00:00:00
abstract：:Population studies have demonstrated that telomere length (TL) displays great diversity among different populations. Previously described controversial findings associated longevity with specific mitochondrial DNA haplogroups (hgs) (e.g., J and U). These observations may be influenced by population diversity, geograph...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2015.01.002
更新日期：2015-01-01 00:00:00
abstract：:We showed earlier that life spans of murine B lymphocytes could be estimated by measuring the functional reactivities of normal B cells upon transfer into x-linked immunodeficient (xid) mice, which do not respond to anti-mouse IgM (anti-mu) antibodies and thymic-independent type-2 (TI-2) antigens. Here the same approa...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(91)90012-o
更新日期：1991-12-02 00:00:00
abstract：:Neutral endopeptidase 24.11 (NEP) inhibitors prevent breakdown of atrial natriuretic peptide (ANP), and may be useful therapeutically, in sodium overload states as often occurs in the aged. However, age-dependent changes in ANP/NEP may limit the activity of these agents in the elderly. To investigate this we conducted...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(01)00264-0
更新日期：2001-09-01 00:00:00
abstract：:Epigenetic modifications, including changes in DNA methylation, have been implicated in a wide range of diseases including neurological diseases such as Alzheimer's. The role of dietary folate in providing methyl groups required for maintenance and modulation of DNA methylation makes it a nutrient of interest in Alzhe...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2017.10.001
更新日期：2018-09-01 00:00:00
abstract：:The protein synthesizing capacity of liver parenchymal cells isolated from 3-, 12-, 24-, 31- and 36-month-old rats was determined by the incorporation of 14C-leucine. Conditions for optimum protein synthesis included the use of an enriched medium (modified Waymouth's MB 752/1) and cell suspension concentrations rangin...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(77)90031-8
更新日期：1977-07-01 00:00:00
abstract：:Chronic health conditions are commonplace in older populations. The process of aging impacts many of the world's top health concerns. With the average life expectancy continuing to climb, understanding patterns of morbidity in aging populations has become progressively more important. Cancer is an age-related disease,...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2017.05.002
更新日期：2017-06-01 00:00:00
abstract：:The intralobular distribution of three lysosomal enzymes, acid phosphatase, N-acetyl-beta-D-glucosaminidase, and beta-D-glucuronidase, was investigated in hepatocytes of 3-, 12-, 24-, and 36-month-old rats. The distribution pattern changed with age. In young rats, the activity was higher in the peripheral area than in...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(83)90109-4
更新日期：1983-06-01 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：: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：:Preclinical and clinical studies suggest that specific subsets of cells isolated from the peripheral blood, play an essential role in the imbalance of damage and repair during age-associated diseases, such as metabolic syndrome, diabetes, atherosclerosis, neurodegenerative diseases, osteoporosis and cancer. Endogenous...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2016.03.005
更新日期：2016-10-01 00:00:00
abstract：:The most relevant theories on the sex-dependent longevity at population level are critically re-examined in the light of the knowledge available today on the aging process at cellular and molecular level. The aim of this perspective is to help in the understanding of the cellular and molecular bases of longevity and t...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/0047-6374(93)90091-5
更新日期：1993-12-15 00:00:00
abstract：:The number of senescent cells in the skin is increasing with age. Numerous studies have attempted to elucidate the role of these cells in normal aging of the skin as well as in age-related skin conditions. In recent years, attempts have also been made to find treatments that aim either to cleanse the skin tissues of s...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2020.111409
更新日期：2021-01-01 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：: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：:Mouse mammary gland displays an irreversible decline in growth rate when propagated by serial transplantation in gland-free mammary fat pads of isogeneic mice. Because transplanted fragments of gland contain both mammary epithelial and stromal elements, the present study was undertaken to distinguish between two possi...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(83)90026-x
更新日期：1983-11-01 00:00:00
abstract：BACKGROUND:The proportion of European elderly is expected to increase to 30% in 2060. Combining dietary components may modulate many processes involved in ageing. So, it is likely that a healthful diet approach might have greater favourable impact on age-related decline than individual dietary components. This paper de...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.mad.2013.10.002
更新日期：2013-11-01 00:00:00
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 agi...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2009.01.001
更新日期：2009-04-01 00:00:00
abstract：:Mitochondrial reactive oxygen species (ROS) and oxidative damage are associated with a range of age-related human pathologies. It is also likely that mitochondrial ROS generation is a factor in stress response and signal transduction pathways. However, current methods for measuring and influencing mitochondrial ROS pr...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2005.03.026
更新日期：2005-09-01 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：:Cultured epiphyseal-chondrocytes from embryonic chick may serve as a useful in vitro model to study aging processes in cartilage. The accelerated aging process in cultured chondrocytes is completed within a month and is manifested by typical changes in both cellular and extracellular compartments. Under common mainten...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(88)90105-4
更新日期：1988-11-14 00:00:00
