Abstract：
:To understand the mechanism of aging at the cellular level, cellular senescence has been extensively studied as an experimental model of aging in vitro. Although several hypotheses have been proposed for the mechanism of cellular senescence, none of them could give a comprehensive framework to the mechanism. In this study, we showed our results of extensive computer simulation designed to identify possible molecular models of cellular senescence. By examining representative cases of various molecular models, we elucidated the requirements for the plausible mechanism of cellular senescence. Based on these simulation results, we proposed a new molecular model of cellular senescence--the two-process model. In this model, we assumed that two independent, but time-aligned regulatory processes functioned in individual cells. We defined these two processes as S- and C-processes. The S-process mainly determines the rate of decline in the proliferative potential of the cell population. The simulation results suggested that the growth-inhibitory cell-to-cell interaction was required to drive the S-process. The C-process determines the latent proliferative potential of individual cells. The effector genes for the C-process are suggested to be regulated by a certain threshold-type mechanism. Both growth kinetics and senescence-associated gene expression were generated with high accuracy by the combined effect of these two processes. We also succeeded in simulating the effects of simian virus 40 large T antigen and its inducible variant on cellular senescence. From these theoretical considerations, we discuss the validity of the two-process model and the possible involvement of the heterochromatin structure as a determinant of the replicative lifespan of cells.
journal_name
Exp Gerontoljournal_title
Experimental gerontologyauthors
Kitano H,Imai Sdoi
10.1016/s0531-5565(98)00008-4subject
Has Abstractpub_date
1998-08-01 00:00:00pages
393-419issue
5eissn
0531-5565issn
1873-6815pii
S0531556598000084journal_volume
33pub_type
杂志文章abstract：:Aging has a profound effect on the immune system, and both innate and adaptive arms of the immune system show functional decline with age. In response to infection with intracellular microorganisms, old animals mobilize decreased numbers of antigen-specific CD8+ T cells with reduced production of effector molecules an...
journal_title：Experimental gerontology
pub_type： 杂志文章,评审
doi：10.1016/j.exger.2018.01.011
更新日期：2018-05-01 00:00:00
abstract：:Estrogens are potent and efficacious neuroprotectants both in vitro and in vivo in a variety of models of neurotoxicity. We determined the structural requirements for neuroprotection in an in vitro assay using a panel of >70 novel estratrienes, synthesized to reduce or eliminate estrogen receptor (ER) binding. We obse...
journal_title：Experimental gerontology
pub_type： 杂志文章,评审
doi：10.1016/j.exger.2016.10.013
更新日期：2017-08-01 00:00:00
abstract：:Numerous trials have shown that physical activity and exercise training have beneficial effects in general older populations. However, few have studied its effectiveness among people with dementia. The aim of this systematic review is to examine the efficacy of trials using a rigorous randomised, controlled design and...
journal_title：Experimental gerontology
pub_type： 杂志文章,评审
doi：10.1016/j.exger.2012.08.008
更新日期：2013-01-01 00:00:00
abstract：:Fetal and placental weights and peripheral blood progestagen concentrations were examined on days 13, 16 and 22 of gestation in young (3-5 month) nulliparous and old (9-12 month) multiparous, albino Wistar rats. There was no difference in fetal weights at any stage examined whereas placental weights were significantly...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/0531-5565(87)90004-0
更新日期：1987-01-01 00:00:00
abstract：:Telomerase plays an important role in cellular proliferation capacity and survival under conditions of stress. A large part of this protective function is due to telomere capping and maintenance. Thus it contributes to cellular immortality in stem cells and cancer. Recently, evidence has accumulated that telomerase ca...
journal_title：Experimental gerontology
pub_type： 杂志文章,评审
doi：10.1016/j.exger.2009.05.004
更新日期：2009-08-01 00:00:00
abstract：:Telomeres are specialised structures located at the end of eukaryotic chromosomes, that get short during progressive cell divisions. Therefore, telomere may be an indicator of the mitotic history of a cell and it is also a determining factor for the residual cell life span. One mechanism, compensating for the telomere...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/s0531-5565(03)00058-5
更新日期：2003-06-01 00:00:00
abstract：:In the present study, using RNA gel-blot analysis, we characterized the developmental changes in the prevalence of mRNA coding for fibronectin (FN), glial fibrillary acidic protein (GFAP), neurotrophic protein S100 beta, and beta-actin mRNA in rat hippocampus and forebrain from 1 to 720 days of age. We found that the ...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/0531-5565(93)90003-v
更新日期：1993-03-01 00:00:00
abstract：:Aging is associated with increased cellular levels of lipid peroxides and reactive oxygen species. This increase in the radical species may affect membrane fluidity and consequently membrane functions. We attempted to determine whether age-related increases in lipid peroxide and reactive oxygen species levels affect t...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/s0531-5565(01)00164-4
更新日期：2001-12-01 00:00:00
abstract：:Reactive oxygen species (ROS) are formed in all living organisms as a by-product of normal metabolism (endogenous sources) and as a consequence of exposure to environmental compounds (exogenous sources). Endogenous ROS are largely formed during oxidative phosphorylation in the mitochondria and, therefore, mitochondria...
journal_title：Experimental gerontology
pub_type： 杂志文章,评审
doi：10.1016/s0531-5565(02)00142-0
更新日期：2002-10-01 00:00:00
abstract：:Muscle wasting diseases are gradually increasing with the increase in global life expectancy. This study was designed to evaluate the efficacy of HIM-CHX, a herbal combination of Boswellia serrata, Cissus quadrangularis, and Withania somnifera, on Sarcopenia. The effects of HIM-CHX on parameters such as muscle mass, g...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2019.110663
更新日期：2019-10-01 00:00:00
abstract：:Fish provide enormous spectrum of longevity and thus present the possibility of multiple mechanisms of senescence. Oxidative stress as a causative agent of senescence and the protective role of antioxidant enzymes were tested in the teleost, Channa punctatus taking peroxidase (POD) (EC 1.1 1.1.7) as the representative...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/s0531-5565(99)00021-2
更新日期：1999-06-01 00:00:00
abstract：:Mouse models have been widely used in the research of human diseases. Aging, just as cancer, is influenced by the interaction of various genetic and environmental factors. Currently, aging could be induced by many mechanism, including telomere dysfunction, oxidase stress, DNA damage and epigenetic changes. Many of the...
journal_title：Experimental gerontology
pub_type： 杂志文章,评审
doi：10.1016/j.exger.2019.03.002
更新日期：2019-06-01 00:00:00
abstract：:Given the increased concerns about the degenerative decline in the physical performance of the elderly, there is a need for developing effective strategies to suppress the age-related loss of skeletal muscle mass and functional capacity through a lifestyle intervention. This randomized controlled trial examined whethe...
journal_title：Experimental gerontology
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.exger.2016.11.003
更新日期：2017-01-01 00:00:00
abstract：:Delirium is an acute-onset syndrome that exacerbates patients' condition and significantly increases consequential morbidity and mortality. There is no comprehensive, cellular and tissue-level, pathophysiological theory. The melatonin hormone imbalance has been shown to be linked to circadian rhythms, sleep-wake cycle...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2015.09.007
更新日期：2015-12-01 00:00:00
abstract：OBJECTIVE:Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs). METHODS:Alzheimer's Disease Neuroimaging Initiative cohort (ADNI...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2017.01.025
更新日期：2017-04-01 00:00:00
abstract：:We have isolated a senescence-specific clone (pSEN) from a cDNA library constructed from late passage WI-38 human diploid fibroblast that accounts for approximately 1% of the recombinants. Nucleotide sequence analysis of the partial cDNA clone has led to the identification of pSEN as elongation factor I alpha. Norther...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/0531-5565(89)90056-9
更新日期：1989-01-01 00:00:00
abstract：BACKGROUND/OBJECTIVES:Geriatric patients are highly susceptible to infections. While reduced lymphocyte count has been associated with age, other studies found no change in WBC counts with age. Increased circulating white blood cell (WBC) count has been associated with cardiovascular (CV) diseases and frailty but there...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2014.11.016
更新日期：2015-01-01 00:00:00
abstract：:The purpose of this study was to examine the effect of a mentally fatiguing task on postural responses to unexpected backward perturbations in sixteen young and sixteen older women. Postural responses were characterized by center of pressure (COP) displacement, corrective COP peak velocity, and electromyography (EMG) ...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2020.110840
更新日期：2020-04-01 00:00:00
abstract：:Aging is characterized by the progressive decline in mass and function of the skeletal muscle along with increased susceptibility to inflammation, oxidative stress, and atrophy. In this study, we investigate the effect of intermittent bout and single bout exercise training on inflammatory molecules in young (3 months)...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2015.11.001
更新日期：2015-12-01 00:00:00
abstract：:Life table aging rate (LAR) is defined as the age-specific rate of mortality change with age and corresponds to the first derivative or slope of the mortality schedule at each age. We computed the sex-specific LARs for 167 Medfly cohorts, containing a total of approximately 600,000 individuals of each sex. We found th...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/0531-5565(94)00041-z
更新日期：1995-05-01 00:00:00
abstract：:There is currently no test to directly and easily measure dynamic balance during walking in old adults. We examined the idea that distance of beam walking with and without cognitive dual-tasking could detect age differences in dynamic balance. Healthy old (n = 16, 71.2 y) and young (n = 20, 22.0 y) volunteers walked 3...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2018.10.016
更新日期：2018-12-01 00:00:00
abstract：:Primary cultures of hepatocytes are widely used to investigate liver function, but this technology has not been exploited fully in the study of ageing and caloric restriction (CR). Hepatocytes were isolated from adult and aged, fully fed, and calorie restricted male Sprague-Dawley rats and their viability and biochemi...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/s0531-5565(00)00101-7
更新日期：2000-08-01 00:00:00
abstract：:Several factors involved in regulation of bone mineral metabolism were compared in male and female Fischer 344 rats of different ages (1, 2.5, 6, and 18 months). Plasma 1,25-(OH)2D3 concentrations decreased with age in rats of both genders. Abundance of calbindin-D28K and its mRNA in kidney and calbindin-D9K and its m...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/0531-5565(95)00014-3
更新日期：1995-11-01 00:00:00
abstract：:The alterations of the lipid composition and fluidity of liver plasma membranes as well as the activity of membrane-bound phospholipase A2 (EC 3.1.1.4) in male and female rats of different ages are investigated. An age-induced increase of the protein/phospholipid and cholesterol/phospholipid ratios is observed, as wel...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/0531-5565(86)90072-0
更新日期：1986-01-01 00:00:00
abstract：:The Senescence-Accelerated Mouse (SAM) strains are unique and appropriate models for genetic studies on aging because the SAMP strains have an "accelerated senescence" phenotype for which the SAMR strains are controls, and each SAMP strain has a strain-specific age-associated disorder. Furthermore, because they have g...
journal_title：Experimental gerontology
pub_type： 杂志文章,评审
doi：10.1016/s0531-5565(96)00060-5
更新日期：1997-01-01 00:00:00
abstract：:Female mammals undergo natural fluctuations in sex steroid hormone levels throughout life. These fluctuations span from early development, to cyclic changes associated with the menstrual or estrous cycle and pregnancy, to marked hormone flux during perimenopause, and a final decline at reproductive senescence. While t...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2016.12.011
更新日期：2017-08-01 00:00:00
abstract：:Non-insulin dependent diabetes mellitus (NIDDM) has been associated with a number of physiological consequences including neuropathy, retinopathy and incidence of vascular disease. Recently, several authors reviewed studies that suggested that NIDDM is associated with cognitive impairments leading to a higher incidenc...
journal_title：Experimental gerontology
pub_type： 杂志文章,评审
doi：10.1016/s0531-5565(03)00153-0
更新日期：2003-09-01 00:00:00
abstract：:Young rhesus monkey females (Macaca mulatta) demonstrate the well-defined circadian rhythm in activity of erythrocyte SOD with maximum at 10.00 h and minimum at 22.00 h. However, neither GSH-Px nor GR demonstrated any significant circadian changes, contrastingly to SOD. The diurnal changes in the SOD activity tightly ...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/j.exger.2006.04.006
更新日期：2006-08-01 00:00:00
abstract：:Working from the hypothesis that modest deviations from physiological oxygen tension will influence cell characteristics important for infections/immunity and tumor development, cells were studied at three oxygen tensions during in vitro aging. Primary mouse embryo fibroblasts were established and subsequently passage...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/0531-5565(93)90046-g
更新日期：1993-11-01 00:00:00
abstract：:Histological surveys of the hearts of guppies Poecilia reticulatus throughout their lifespan showed no aging changes until the fish were three years old. In younger fishes the hearts were healthy, even in three individuals with "wasting" disease, where there was considerable loss of muscle throughout the body. There w...
journal_title：Experimental gerontology
pub_type： 杂志文章
doi：10.1016/0531-5565(84)90048-2
更新日期：1984-01-01 00:00:00
