Abstract:
:This study attempts to elucidate the molecular mechanisms underlying the ageing-dependent cAMP profiles in human diploid fibroblasts stimulated by lysophosphatidic acid (LPA). In senescent cells, LPA-dependent Gialpha activation was reduced, with a consequent reduction in Gi-suppressed cAMP levels, without alterations in the levels of Gialpha proteins. In young cells, when Gialpha activity was inhibited by pertussis toxin pretreatment, or when its expression was blocked by siRNA, the pattern of changes in cAMP levels in response to LPA was similar to that seen in senescent cells. An increase in protein kinase C (PKC)-dependent isoforms of adenylyl cyclase (AC) types II, IV, and VI was also observed in these senescent fibroblasts. In senescent cells treated with PKC-specific inhibitors, bis-indolylmaleimide, Gö6976, rottlerin, and PKCvarepsilonV1, LPA-induced cAMP accumulation was inhibited, indicating that increased ACs in response to LPA occur via the activation of protein kinase Cs. When the expression of AC II, IV, and VI was blocked by siRNA in senescent fibroblasts, LPA-induced cAMP accumulation was also blocked. These results suggest that the senescence-associated increase of cAMP levels after LPA treatment is associated with reduced Gialpha, increased AC II, IV, and VI proteins, and PKC-dependent stimulation of their activities and provide an explanation for the age-dependent differences in cAMP-related physiological responses.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Jang IS,Rhim JH,Kim KT,Cho KA,Yeo EJ,Park SCdoi
10.1016/j.mad.2006.01.004subject
Has Abstractpub_date
2006-05-01 00:00:00pages
481-9issue
5eissn
0047-6374issn
1872-6216pii
S0047-6374(06)00015-7journal_volume
127pub_type
杂志文章abstract::Experimental studies have not shown that the 'common' clinical experience, which suggests that wound healing is impaired in an old organism, is valid for healthy old experimental animals. We have developed a model in the rat for ischemic wound healing by using an H-shaped double skin flap, where the test wound is the ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(91)90094-g
更新日期:1991-05-01 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
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::A comparison was made of the resting membrane potential (MP) as well as the MP responses to K+, ACTH and gamma-MSH of superfused adrenocortical, zona fasciculata cells from young (Y) and old (O) male rats. The resting MP of these cells did not vary with age. However, the MP responses to altered extracellular [K+] vari...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(88)90036-x
更新日期:1988-06-01 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::It strikes me that among our relatively small community of gerontologists concerned with genetic approaches to our science, there is somewhat of a dichotomization. On the one hand, there are those of us, like myself, who tend to be dour 'complificationists'. Journalists talk to us, but are usually disappointed by the ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/s0047-6374(01)00335-9
更新日期:2002-01-01 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::Werner syndrome (WS) is a premature aging and cancer-prone disease caused by loss of the RecQ helicase WRN protein. Cultured WS fibroblasts display high genomic instability and senesce prematurely. Epigenetic inactivation of the WRN gene occurs in numerous tumor types, in which WRN demonstrates tumor suppressor-like a...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2007.05.009
更新日期:2007-07-01 00:00:00
abstract::In agreement with previous studies we show an age-related increase in serum levels of hyaluronic acid in healthy individuals. Levels in Down's syndrome persons were slightly higher, especially in those with hypothyroidism. This provides further evidence that the normal ageing process is accelerated in Down's syndrome....
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(98)00112-2
更新日期:1998-12-01 00:00:00
abstract::The effects of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and lipopolysaccharide (LPS) on the productions of nitric oxide (NO) and cGMP by cultured articular chondrocyte (AC) monolayers from 1-, 8- and 18-month old male Wistar rats were studied. It was found that basal NO and cGMP productions decre...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(97)00150-4
更新日期:1998-03-16 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 process of epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) after cataract surgery contributes to tissue fibrosis, wound healing and lens regeneration via a mechanism not yet fully understood. Here, we show that tropomyosin 2 (Tpm2) plays a critical role in wound healing and lens aging. Post...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2018.03.001
更新日期:2018-04-01 00:00:00
abstract::The binding of the lectin Concanavalin-A (Con-A) to crystallins was investigated. For this purpose, human fetal and juvenile lens crystallins were isofocused and specifically stained brown for glycoproteins by the lectin Con-A, and purple by the periodic acid Schiff's reagent (PAS). In reference experiments protein ba...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(97)00097-3
更新日期:1997-12-30 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::The oral health of older people is changing with reducing numbers of people relying on complete dentures for function, and retaining some natural teeth. Despite this there are substantial numbers of older people whose ability to chew foods is compromised by their oral health status, either because they have few or no ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/j.mad.2004.07.011
更新日期:2004-12-01 00:00:00
abstract::Rats of two age groups (6 weeks and 30 months) received (1) a single dose of 600 mg D-galactosamine (GalN)/kg body weight by intraperitoneal (i.p.) injection, (2) a single dose of 600 mg GalN/kg body weight i.p. combined with 20 mg prednisolone/kg body weight subcutaneously at the beginning of the experiment. The kine...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(78)90064-7
更新日期:1978-03-01 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::Previous studies have suggested a possible relationship between the ubiquitin-proteasome pathway and some pathological manifestations of Alzheimer's disease (AD). This study investigated the possibility that the Abeta peptides interact with the ubiquitin-proteasome pathway inside neuronal cells. The ubiquitin-proteaso...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2005.07.006
更新日期:2005-12-01 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::Chronic oxidative stress is generally believed to be a major etiologic factor in the aging process. In addition to modulation of signaling processes and oxidation of cellular proteins and lipids, reactive oxygen species (ROS) induce multiple damages in both nuclear and mitochondrial genomes, most of which are repaired...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2004.07.005
更新日期:2004-10-01 00:00:00
abstract::Age-related variations in the stromal cell population of human bone marrow were studied by means of a cloning assay. It was found that these cells are heterogeneous both in division capacity and in morphology. Fibroblast-like progenitor cells could be distinguished from epithelial-like cells, having only a very limite...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(81)90006-3
更新日期:1981-01-01 00:00:00
abstract::Age-specific mortality rates from breast cancer (BC) in Japan from 1950 through 1993 were subjected to longitudinal Gompertzian and Weibull analyses. Age-specific BC mortality rate distributions between the ages of 30 and 75 years were Gompertzian in each year. Between 1950 and 1993, age-adjusted BC mortality rates in...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(96)01735-6
更新日期:1996-07-17 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::Morphometric comparison of freeze-fractured mitochondria in flight muscles of adult (37-day-old) and old (68-day-old) houseflies revealed a 28% decrease of cristae in the old flies. The major membrane change with age was an increase in the 90-120-A particles in the inner membrane external face concomitant with a loss ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(81)90095-6
更新日期:1981-06-01 00:00:00
abstract::A subset of 43 [35S]methionine labeled mitochondrial proteins, identified on two dimensional electrophoresis gels of whole body extracts of adult Drosophila, were compared between two age groups. These flies, which except for their spermatocytes consist entirely of postmitotic cells, were 6 days old and 38 days old, w...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(86)90105-3
更新日期:1986-03-01 00:00:00
abstract::The present study examined the effect of repeated vaccination and of dehydroepiandrosterone (DHEA) treatment on the immune response to influenza vaccine in elderly subjects. Seventy-one elderly volunteers, aged 61-89 years, enrolled in a prospective randomized, double-blind study to receive either DHEA (50 mg qd p.o. ...
journal_title:Mechanisms of ageing and development
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0047-6374(98)00017-7
更新日期:1998-05-15 00:00:00
abstract::Lipid peroxidation, one of the most common expressions of oxidative stress, may be altered during normal physiological states including development. We have examined the changes in lipid peroxidation in rat brain, a tissue highly susceptible to oxidative damage, during this physiological state. In vivo lipid peroxidat...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(94)90052-3
更新日期:1994-03-01 00:00:00
abstract::We have examined newly synthesized proteins in the young adult and in older populations of the nematode Caenorhabditis elegans using two-dimensional polyacrylamide gel electrophoresis (2D PAGE). A temperature-sensitive mutant strain, DH26, with a mean life span of about 15 days, under our conditions, was used to block...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(85)90118-6
更新日期:1985-05-31 00:00:00
abstract::The basic genetic defect in the Hutchinson-Gilford Progeria Syndrome (progeria), a premature aging syndrome, is unknown. To investigate possible defects in hyaluronic acid (HA) metabolism in this disease, the urinary excretion of HA was studied. Urine specimens from 11 patients with this disorder were examined for HA ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(86)90064-3
更新日期:1986-06-01 00:00:00
abstract::A pronounced suppression of the humoral, hemolytic, primary immune response in old (22 months) mice was demonstrated as compared with this response in young (10 weeks) mice. The suppression is associated with a lower thymus weight:body weight ratio. In contrast, the ratios spleen weight:body weight and liver weight:bo...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(78)90065-9
更新日期:1978-03-01 00:00:00