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 of MRC-5 human embryo lung fibroblasts. The frequency increased substantially during the lifespan of the culture and regression analysis shows that the increase is exponential. No increase invariant frequency was found in a immortal transformed line cultured for over 100 passages. Evidence is presented that the variants are regulatory mutations. This is the first direct evidence for the involvement of presumed somatic mutations in the ageing of mammalian cells. 5-Fluorouracil but not p-fluorophenylalanine shortened the life of the cells and increase the variant frequency. The data lend support to a model in which mutations are an expected consequence of errors in protein synthesis.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Fulder SJdoi
10.1016/0047-6374(79)90074-5subject
Has Abstractpub_date
1979-04-01 00:00:00pages
101-15issue
1-2eissn
0047-6374issn
1872-6216pii
0047-6374(79)90074-5journal_volume
10pub_type
杂志文章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 age-related deficit in the dose response of osteoprogenitor cells to IGF-I was further investigated. As expected, the effective dose, but not the maximal effect, was shifted two orders of magnitude higher in old cells. In this paper, we examined whether this age-deficit can be attributed to an alteration in the ex...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(96)01793-9
更新日期：1996-11-29 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：:Confluent late passage WI-38 human diploid fibroblast cultures grown in the presence or absence of hydrocortisone for fifteen population doublings were measured cytochemically for DNA, nuclear RNA, basic nuclear protein and acidic nuclear protein content during a 12-hour interval following a medium-change stimulation....
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(81)90059-2
更新日期：1981-11-01 00:00:00
abstract：:In this paper we investigate nucleic acid content in neurons from the dorsocaudal region of the thalamic reticular nucleus in ageing Wistar rats. Nucleic acid per surface unit was analysed by calculating mean extinction using cytophotometric methods. Once the mean extinction and nuclear and cytoplasmic areas were know...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(97)00083-3
更新日期：1997-12-01 00:00:00
abstract：:The serotonin content of platelets, serum and plasma from rats of various ages was examined. In male rats, platelet serotonin content, which was about 0.65 nmol/10(8) platelets at young age (6-7 months), increased slightly at middle age (12-14 months) but decreased markedly at old age (25-26 months). Significant diffe...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(89)90008-0
更新日期：1989-01-01 00:00:00
abstract：:This paper presents evidence derived from the selective use of codons in ca. 40 eukaryotic genes (or messages derived from them) that codon usage is one of the most conserved features of messages for specific cell products. The theory has been developed by several investigations that the kinds of products of many if n...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(82)90034-3
更新日期：1982-04-01 00:00:00
abstract：:We have developed a cell model for loss of differentiated gene expression in cellular aging. Over long periods in culture, bovine adrenocortical cells lose expression of a specialized gene, steroid 17 alpha-hydroxylase. The decline in expression of 17 alpha-hydroxylase in mass cultures and clones of bovine adrenocorti...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(91)90115-g
更新日期：1991-04-01 00:00:00
abstract：:The human fibroblast cell line WI-38 shows a gradual decline in glutamine synthetase specific activity with increasing age in culture. However, the level of functional enzyme per cell does not change with age. Heat inactivation profiles indicate that glutamine synthetase from younger cell cultures is more heat labile ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(78)90005-2
更新日期：1978-07-01 00:00:00
abstract：:There are reports demonstrating elevated levels of autoantibodies in elderly people. We now analyzed whether the strong inflammatory response associated with aging is interrelated with the production of autoantibodies, antinuclear antibodies (ANA). In a cohort of 284 nonagenarians the rate of ANA positivity was 12.3%,...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2007.03.001
更新日期：2007-05-01 00:00:00
abstract：:We compared cardiovascular responses to various adrenergic agonists in conscious 3-month and 12-month old rats that had been treated with propranolol daily for 7 days, to determine whether changes in beta-adrenergic hypersensitivity induced by abrupt propranolol withdrawal would differ with age. Depressor and tachycar...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(92)90019-a
更新日期：1992-03-15 00:00:00
abstract：:Food restriction is known to ameliorate many of the adverse physiologic effects of age. In this study, we have examined the effect of food restriction on the induction of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK) in liver and kidney following a 12-h fasting period in young (6 month) and old (...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(98)00075-x
更新日期：1998-09-01 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：:Vascular tree development depends on the timely differentiation of endothelial and vascular smooth muscle cells. These latter are key players in the formation of the vascular scaffold that offers resistance to the blood flow. This review aims at providing an overview on the role of PDE5, the cGMP-specific phosphodiest...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2020.111311
更新日期：2020-09-01 00:00:00
abstract：:Hepatocytes isolated from 6-, 12-, 18-, and 30-month-old female Fischer F344 rats were examined by scanning electron microscopy. No significant change in cell size with age was observed. However, the surface morphology of the cells isolated from the older animals exhibited a significant increase in surface folds. This...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(81)90023-3
更新日期：1981-01-01 00:00:00
abstract：:Putrescine, spermidine, spermine and two unknowns designated as A and B were detected in first seedling leaves of barley (Hordeum vulgare L. var. Wolfe). The levels of these polyamines in first seedling leaves from 4-day-old barley plants grown in darkness or in light were comparable and did not change significantly a...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(87)90031-5
更新日期：1987-09-14 00:00:00
abstract：:The present study aimed to reveal aging-related changes in the skeletal muscle of SD rats by comparing transcriptome analysis, integrated with muscle physiological parameters. Ten rats aged 25 months were set as the old group (OG) and ten rats aged 6 months were set as the young group (YG). After 6 weeks of feeding, t...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2018.01.001
更新日期：2018-01-01 00:00:00
abstract：:Cellular senescence is a phenomenon of irreversible growth arrest in mammalian somatic cells in culture. Various stresses induce cellular senescence and indeed, we have found that excess thymidine effectively induces cellular senescence in human cells. Further, many reports indicate the implication of chromatin protei...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2019.01.001
更新日期：2019-03-01 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：:A few reports suggest that pigmented granules found in molluscan neurons accumulate with age as do lipofuscin granules in vertebrate cells; however, no reports on molluscan neurons include detailed descriptions of granule accumulation or histochemical tests to identify the pigment as lipofuscin-like. In this study lig...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(78)90052-0
更新日期：1978-01-01 00:00:00
abstract：:The activity of rat heart succinate dehydrogenase (SDH) increases 1.7-fold in old animals (Vitorica, J., Cano, J., Satrústegui, J. and Machado, A., Mech. Ageing Dev., 16 (1981) 105-116). This increase is due to an increase in enzyme protein itself because: (a) the activation state of the enzyme does not vary with age;...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(85)90076-4
更新日期：1985-11-01 00:00:00
abstract：:Filopodia in log and stationary phase populations of human fetal lung fibroblasts (WI-38) at low and high population doubling levels (PDLs) and of SV40 transformed WI-38 cells (VA13A), were observed and counted under different conditions of in vitro growth by scanning electron microscopy. Cells from old non-vigorously...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(86)90048-5
更新日期：1986-02-01 00:00:00
abstract：:In this paper we examined the impact of age on cognitive functions and the age-related modifications of egr1 expression, an inducible transcription factor with a confirmed role in synaptic plasticity and regulation of the proteasome activity, on pet dogs. Additionally, we examined the age-related changes of some eleme...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2009.01.007
更新日期：2009-05-01 00:00:00
abstract：:Arteriosclerosis is believed by many to represent the aging process of arteries and to be responsible for the cause-specific deaths at any age in industrialized countries. However, the increasing rate of (A) associated with steadily increasing life expectancy invited studies of the average age at death (AAD) of condit...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(91)90030-4
更新日期：1991-02-01 00:00:00
abstract：:The polyphenol quercetin has recently been found to extend lifespan and increase stress resistance in the nematode Caenorhabditis elegans. The forkhead transcription factor DAF-16 has previously been linked to these effects. However, by using a daf-16(mgDf50) mutant strain, we show that quercetin exposure leads to inc...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2008.07.001
更新日期：2008-10-01 00:00:00
abstract：:The development and aging of the nucleolus and nucleus in layer V pyramidal cells in the hamster cerebrum were studied by light and electron microscopy. The nucleoli appeared in the newborn as occasional fibrillar masses adjacent to peripherally placed bodies of chromatin. By maturity, a single, generally central, nuc...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(81)90043-9
更新日期：1981-04-01 00:00:00
abstract：:Active vitamin D drugs are used for the treatment of osteoporosis in a number of countries, including Japan. However, their use is controversial. Here, we briefly discuss two issues that are important for understanding the role of active vitamin D (rather than plain vitamin D) in the treatment of osteoporosis: (1) whe...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/s0047-6374(00)00115-9
更新日期：2000-07-31 00:00:00
abstract：:The mTOR deregulation has a role in chronic kidney disease including diabetic nephropathy. SIRT1 is an important participant in renal cytoprotective responses to aging and stress. However, whether both mTOR and SIRT1 are involved in high glucose-inducing mesangial cells (MCs) senescence still remains to be explored. H...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2012.04.005
更新日期：2012-06-01 00:00:00
abstract：:The peripheral-type benzodiazepine receptor (PBR) is a protein predominantly located in the mitochondrial outer membrane that plays an important role in the regulation of cell survival and proliferation. Previous studies have shown an enhanced expression of PBR in the regenerating sciatic nerve, suggesting that this p...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2005.06.001
更新日期：2005-11-01 00:00:00
abstract：:Food restriction (FR) may increase longevity by increasing the efficiency of energy utilization by some organs. We tested whether any effect of FR on the energy efficiency of isolated, isovolumically beating hearts could be observed, by studying four groups of rats: (1). AL fed (AL) 10-13-month-old rats, (2). age matc...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(02)00078-7
更新日期：2002-07-01 00:00:00
