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 endocytosis in the membrane might be emphasized as a responsible mechanism for functional decay, since the endocytosis is in charge of many important biological phenomena: nutrient uptake, growth factor sensitivity, immune response, protection from environment and pathogen uptake, etc. We found that two major endocytotic pathways, i.e. clathrin-mediated and caveolae-dependent endocytosis, are down regulated in senescent cells. For the down regulation of the clathrin dependent receptor-mediated endocytosis, the reduction of amphiphysin-1 was found responsible, which was confirmed by Western blot analysis, dominant negative mutant transfection and restoration of gene activity by microinjection. With respect to the hypo-responsiveness of senescent cells to growth factors, the upregulation of caveolins has been suggested to be a causal factor. The overexpression of caveolins caused senescent-like changes in epidermal growth factor (EGF) response of the young cells, while down regulation of caveolins by use of antisense-oligonucleotides restored the EGF response in old cells, suggesting that caveolin system would be one of the major mechanisms responsible for decreased responses to growth factors in the senescent cells. Based on these results, it can be suggested that the functional deterioration of the senescent cells may be explained in terms of the down regulation of receptor mediated endocytosis, at least in part, and that the restoration of endocytosis apparatus either with amphiphysin supplementation or with reduction of caveolins might lead to functional recovery of the senescent cells.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Park SCdoi
10.1016/s0047-6374(02)00029-5subject
Has Abstractpub_date
2002-04-30 00:00:00pages
917-26issue
8eissn
0047-6374issn
1872-6216pii
S0047637402000295journal_volume
123pub_type
杂志文章,评审abstract::To understand the effect of calorie restriction on genome maintenance systems, the age-dependent accumulation of mutations in animals maintained on high and low calorie diets was examined using lacZ-transgenic mice. Mice were fed a diet of 95 kcal/w or 65 kcal/w from 2 to 17 months of age. The mutation frequencies in ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2011.01.004
更新日期:2011-03-01 00:00:00
abstract::An increase in natural (innate) immunity with age (through 65 weeks) of NBR rats to a syngeneic methylcholanthrene-induced fibrosarcoma (MCA) is described. This increase is characterized by the appearance of spontaneous tumor regressor animals and an increase in the incidence of tumor non-takes by rats 45 weeks of age...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(81)90129-9
更新日期:1981-09-01 00:00:00
abstract::We have studied effects of long-term, low-dose growth hormone therapy on the immune function and life expectancy of Balb/c mice. Sixty male Balb/c mice were aged up to the time when they started showing signs of senescence and causal death (deaths started when they became 17 months old). The aged mice were divided int...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(91)90026-v
更新日期:1991-01-01 00:00:00
abstract::Endogenous retroelements, transposons that mobilize through RNA intermediates, include some of the most abundant repetitive sequences of the human genome, such as Alu and LINE-1 sequences, and human endogenous retroviruses. Recent discoveries demonstrate that these mobile genetic elements not only act as intragenomic ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/j.mad.2018.02.002
更新日期:2018-09-01 00:00:00
abstract::In this paper, we approach the problem of attempting to understand senescence by understanding the complexity and hierarchical structure of mammalian organisms. To do this, we make use of some concepts from abstract relational biology; in particular, graph theory. We subsequently utilize these concepts to develop the ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(84)90056-3
更新日期:1984-10-31 00:00:00
abstract::Pituitary adenomas were the most common grossly visible naturally occurring neoplasms found in over 27% of rats surviving beyond 17 months of age. Twenty-three pituitary adenomas, fixed in buffered neutral formalin and embedded in paraffin, were tested for the presence of prolactin (PRL), growth hormone (GH) and thyro...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(82)90065-3
更新日期:1982-10-01 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::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::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::The growing proportion of older people, especially the very old, is often thought of in negative terms such as the need for more health care. But the implications are wider and affect the future of family care as well as issues of intergenerational relations, employment, living arrangements and attitudes. This paper l...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/s0047-6374(01)00418-3
更新日期:2002-04-01 00:00:00
abstract::Iron deficiency anaemia is prevalent in older age, particularly after the age of 80. Serum ferritin concentrations also decline, although there is no evidence to suggest that changes in iron stores are an inevitable consequence of ageing. Chronic inflammation is a common condition in older people, making the measureme...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/j.mad.2013.11.005
更新日期:2014-03-01 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 effect of the oral administration of 0.150 mg/m2 clonidine on the plasma level of human growth hormone (hGH) was studied in 53 adults (25 males and 28 females) aged from 28 to 68 years, of which 15 were healthy volunteers and 38 were hypertensive. Both the normal and hypertensive subjects of both sexes showed an a...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(84)90086-1
更新日期:1984-09-01 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
abstract::In most species, females live longer than males. An understanding of this female longevity advantage will likely uncover novel anti-aging therapeutic targets. Here we investigated the transcriptomic responses in the hypothalamus - a key organ for somatic aging control - to the introduction of a simple aging-related mo...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2019.111150
更新日期:2019-12-01 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::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 investiga...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2011.12.003
更新日期:2012-02-01 00:00:00
abstract::Considerable evidence points to an accumulation of somatic mutations in older cells and organisms but the causal role of mutations in the ageing process is still unclear. In addition to demonstrating that mutations accumulate, it is important to address the question of whether they do so at a sufficient rate and with ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/s0047-6374(02)00177-x
更新日期:2003-01-01 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::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::Classical evolutionary theory predicts the existence of genes with antagonistic effects on longevity and various components of early-life fitness. Quantitative genetic studies have provided convincing evidence that such genes exist. However, antagonistic pleiotropic effects have rarely been attributed to individual lo...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/j.mad.2004.07.012
更新日期:2005-03-01 00:00:00
abstract::Metabolite concentrations in gastrocnemius and soleus muscles were compared in young-adult (4 months), mature (12 months) and senescent (24 months) rats after continuous (72 consecutive hours) exposure to normobaric hypoxia or normoxia with the intraperitoneal administration of the vasodilator naftidrofuryl or saline ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(90)90051-g
更新日期:1990-06-01 00:00:00
abstract::It has been previously well documented that partial pressure of oxygen (PO2) and weight-specific rate of O2 consumption in chick embryo (Gallus gallus domesticus) transiently increase midway through the 21-day in ovo incubation period. The present study found that these oxidative changes were paralleled by the concent...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(92)90125-w
更新日期:1992-08-01 00:00:00
abstract::The effect of various immunosuppressive treatments on mean life-span and disease incidence have been studied. Significant life shortening was seen only in mice which recieved X-irradiation early in life and can be ascribed primarily to an increased incidence of certain malignancies. Marginal life shortening was seen i...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(75)90027-5
更新日期:1975-05-01 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 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::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::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::We investigated mitochondrial ageing in a temperate (Mya arenaria) and an Antarctic (Laternula elliptica) mud clam, with similar lifestyle (benthic filter feeders) but different maximum life spans (MLSP), 13 and 36 years, respectively. The short-lived temperate M. arenaria showed a more pronounced decrease in mitochon...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2005.02.002
更新日期:2005-05-01 00:00:00
abstract::In this paper, some of the key findings of the last decade will briefly be surveyed and, where possible, be related to two separate computer simulation models which have been designed to determine the validity of certain widely accepted dogmas and to define the limits and restrictions imposed by attrition of or ambigu...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(80)90103-7
更新日期:1980-09-01 00:00:00