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 the affected bcl-2 deficient kidneys on the postnatal development and lifespan of bcl-2 knockout mice we used "the rescue of (n-1) affected tissues" strategy. According to this strategy bcl-2 heterozygous animals were crossed with H2K-hbcl-2 transgenic mice expressing human BCL-2 in most tissues and organs excluding the kidney. Overexpression of hBCL-2 in bcl-2-/- mice rescues growth retardation, normalizes and protects the hematolymphoid system from gamma-radiation. However, the hbcl-2 transgene is not expressed in kidneys and the rescued mice have PKD and a shortened lifespan. Thus, our results indicated that PKD is the main reason of early mortality in bcl-2 deficient mice. Moreover, we have created mouse model, similar to the kidney specific knockout of bcl-2. Such models can be useful to study the influence of bcl-2 or other gene deficiency in individual organs (or tissues) on development and ageing of whole organism.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Fedorov LM,Schmittwolf C,Amann K,Thomas WH,Müller AM,Schubert H,Domen J,Kneitz Bdoi
10.1016/j.mad.2006.02.009subject
Has Abstractpub_date
2006-07-01 00:00:00pages
600-9issue
7eissn
0047-6374issn
1872-6216pii
S0047-6374(06)00068-6journal_volume
127pub_type
杂志文章abstract：:Previous studies on DNA repair in ageing have demonstrated increased frequencies of single and double strand breaks in lymphocytes from elderly subjects and, as a consequence, decreased efficiency in DNA replication. We have investigated the relationship between cell proliferation and the nuclear expression of ku prot...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(97)00137-1
更新日期：1998-01-30 00:00:00
abstract：:Motor neurons and ventral root motor fibres innervating extensor digitorum longus (EDL) muscle in rats of 0.5-3.5 months of age were studied by HRP-retrograde labelling and in vivo muscle tension recording, respectively. EDL nucleus size increased with age but motor neurons number and size did not change. Twitch and t...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(96)01839-8
更新日期：1996-12-20 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
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：:The age-related changes in the distribution of enkephalin-immunoreactive (ENK-IR) nerve fibers in relation to the principal neurons were studied in 23 human sympathetic ganglia from patients aged between 22 and 98 years. There were no age-related changes in the diameter of nerve cells and the packing density of the ne...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(88)90086-3
更新日期：1988-08-01 00:00:00
abstract：:Prostaglandin (PG) synthesis by human embryo lung fibroblasts in culture was determined with increasing population doubling. These cultures synthesized PGE2, PGF2 alpha, PGI2 (prostacyclin) and TXA2 (thromboxane A2) in response to fetal bovine serum or ascorbic acid. Changes in prostaglandin synthesis by these cells d...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(80)90063-9
更新日期：1980-04-01 00:00:00
abstract：:A major cause of ageing is thought to be the accumulation of damage to macromolecules. Accumulation to DNA damage in cells therefore presupposes that aged cells are unable to repair this damage. We have used the in vitro model of cellular ageing to test the idea that senescent cells are deficient in some aspect of DNA...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2004.12.002
更新日期：2005-06-01 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：:To explore whether catecholaminergic lesions produced chemically in the nucleus tractus solitarius (NTS) would alter the baroreflex impairment that normally occurs with age, we compared baroreflex responses in 3- and 14-month-old rats given bilateral microinjections of 6-hydroxydopamine (6-OHDA) or its vehicle into th...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(92)90097-w
更新日期：1992-06-01 00:00:00
abstract：:Human diploid cells, TIG-7, were serially cultivated under 1%, 5% or 21% (air) oxygen. The limit of their cumulative population doublings was extended by 16% or 10% under 1% or 5% oxygen, respectively, as compared with that under 21% oxygen. When TIG-7 cells were serially cultivated in the presence of 10 mM or 20 mM 3...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(95)01584-m
更新日期：1995-07-14 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：: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：:Hormone responsiveness is mediated by signal transduction mechanisms involving second messengers, such as cAMP and Ca2+, which regulate reversible changes in the phosphorylation state of proteins. During senescence individuals frequently exhibit a diminished responsiveness to hormones. We examined changes in enzymes i...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(88)90125-x
更新日期：1988-12-01 00:00:00
abstract：BACKGROUND:It seems to be clear that hepatic age-related HMG-CoA reductase total activation is connected to a rise of reactive oxygen species (ROS). However, the mechanism by which ROS achieve this effect is unknown. Thus, in this work, we have performed a study of HMG-CoAR by analyzing the enzymes involved in its shor...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2007.10.001
更新日期：2007-11-01 00:00:00
abstract：:It has been shown in several studies that 2-mercaptoethanol (2-ME) improves the life span and aspects of life performance of laboratory animals. To obtain further details on the beneficial effects of 2-ME, a long-term study has been performed on male CBA/Ca inbred mice treated with this antioxidant. Four month-old mic...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(88)90021-8
更新日期：1988-10-01 00:00:00
abstract：:The aim of this study was to investigate the effect of physical training on balance, strength, and general well-being in adult people with intellectual disability (ID). This study evaluated how physical training can effect physical and psychological change among 'older' adults with mild ID. Participants consisted of n...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2004.08.021
更新日期：2005-02-01 00:00:00
abstract：:Evolution of longevity of the ungulates, carnivores and primates is reviewed. Special emphasis is focused on recent evolutionary history of longevity along the hominid ancestral-descendant sequence leading to modern man. Maximum life span potential (MLP) or the change in MLP is predicted in extinct species by (1) a ph...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/0047-6374(79)90110-6
更新日期：1979-02-01 00:00:00
abstract：:The effects of aging on the activation of the cytoplasmic tyrosine protein kinase p56(lck) have been investigated in PBL from adult and elderly subjects upon activation with mitogens or different co-stimuli. Results show that the amount and phosphorylation of p56(lck) are reduced in PBL from elderly as compared to adu...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(97)00144-9
更新日期：1998-05-15 00:00:00
abstract：:In this paper, I attempt to address the problem of how to model the survival curve in the early lifespan years; the neonatal years. I present a general model for a two group population in which the first group represents early stage failure and the second group represents the classical Gompertzian failure. After calcu...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(86)90026-6
更新日期：1986-01-01 00:00:00
abstract：:Age-specific mortality from carcinoma of the prostate was analyzed by drawing a line between the value at age 52 years and that at age 87. Slope of the line was relatively constant for the pooled years 1962-1966, 1967-1971 and 1972-1976 (maximum variation from the mean of 4.5%). However, the slope was 17.7% greater fo...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(95)01608-3
更新日期：1995-08-31 00:00:00
abstract：:We have previously reported that two or more different subpopulations of bone marrow stem cells exist in mice as determined by cycling status of day-8 and day-14 CFU-S in long term bromodeoxyuridine (BrdU) infusion studies. In the present report, comparisons between cycling of stem cell subpopulations in old and young...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(89)90069-9
更新日期：1989-07-01 00:00:00
abstract：:The impairment of brown adipose tissue (BAT) thermogenic activity with aging has been well documented. The current study investigated the effect of swimming training on BAT activity in 2-month-old (young) and 26-month-old (old) male mice. The trained mice underwent a 6-week swimming program (1 h/day, 5 days/week) in w...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(96)01727-7
更新日期：1996-08-15 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：:The present report analyzes the suppressor cell system of aged rats in an experimental model of autoimmunity to rat male accessory glands (RAG). A state of specific suppression to RAG was induced when young rats are pretreated with peritoneal cells (PC) obtained from syngeneic young rats i.p. injected 2 h previously w...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(94)90005-1
更新日期：1994-10-01 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：: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：:Alteration of T cell surface marker expression with a decrease of CD3 positive cells relative to the number of CD4 and CD8 positive cells, diminished in vitro proliferative response to mitogenic stimuli like PHA and antibodies to the CD3/Ti complex, and increase in serum IL-2 receptor levels, are among the changes in ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(88)90045-0
更新日期：1988-05-01 00:00:00
abstract：:Rats from one month to 22 months of age were subjected to in vivo brain microdialysis under a free-moving condition. The 3,4-dihydroxyphenylacetic acid level in the striatum reached a maximum at 3 months old. However, both basal and potassium-induced dopamine release were maximal at 1.5 months, which represents sexual...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(95)01680-5
更新日期：1996-02-24 00:00:00
abstract：:The present study investigated whether age-related changes in the production of Th1 and Th2 cytokines by human T cells might be linked to altered frequencies of naive (CD45RA+) and memory (CD45RO+) T cell subsets. T cells from healthy elderly humans (n = 32) stimulated with anti-CD3epsilon monoclonal antibody OKT3 plu...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(99)00030-5
更新日期：1999-08-30 00:00:00
abstract：:The effect of aging on patterns of food intake and nutrient selection was investigated using a longitudinal study. Male (n = 10) and female (n = 10) Wistar-Lou rats from 4 to 28 months of age were repeatedly submitted to a macronutrient self-selection (S-S) regimen while controls were maintained under a standard chow ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(98)00013-x
更新日期：1998-07-15 00:00:00
