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 a dynamic profile that is consistent with them playing a causative role. We describe the development of in silico models that can be used to explore the role of somatic mutations in ageing and which form a part of a growing effort to build predictive mathematical and computer models that can help unravel the complexity of the functional genomics of ageing. Our models address, in particular, how mutations affect populations of dividing cells like human fibroblasts, in which the challenge to the somatic mutation theory is greatest, since selection at the cellular level will tend to suppress the accumulation of mutations.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Kirkwood TB,Proctor CJdoi
10.1016/s0047-6374(02)00177-xsubject
Has Abstractpub_date
2003-01-01 00:00:00pages
85-92issue
1eissn
0047-6374issn
1872-6216pii
S004763740200177Xjournal_volume
124pub_type
杂志文章,评审abstract：:Older adults who are at risk of developing influenza illness, have a low level of influenza virus-stimulated cytotoxic T lymphocyte (CTL) activity as measured by an assay of granzyme B (GrB). The purpose of this study was to determine whether aging affected memory CTL populations identified by GrB expression in influe...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2007.05.001
更新日期：2007-05-01 00:00:00
abstract：OBJECTIVES:To investigate whether systemic inflammation in acutely admitted older medical patients (age >65 years) is associated with physical performance and organ dysfunction. Organ dysfunction´s association with physical performance, and whether these associations are mediated by systemic inflammation, was also inve...
journal_title：Mechanisms of ageing and development
pub_type： 临床试验,杂志文章
doi：10.1016/j.mad.2017.04.005
更新日期：2017-06-01 00:00:00
abstract：:Overproduction of oxidants and free radicals in ageing tissues induces nitro-oxidative stress, which has recently been implicated in the pathogenesis of cardiovascular dysfunction associated with ageing. Peroxynitrite, a strong cytotoxic oxidant damages proteins and DNA and activates several pathways causing tissue in...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2006.09.005
更新日期：2007-02-01 00:00:00
abstract：:Long-term cultures of human umbilical endothelial cells were examined for changes in cell growth, cell density, cell volume, occurrence of multinucleated cells, prostacyclin production and negative charge of the cell surface during in vitro cellular ageing. The changes observed were consistent with the previously desc...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(88)90119-4
更新日期：1988-12-01 00:00:00
abstract：:The hypothesis that aging is associated with the accumulation of oxidative damage was tested in the adult male housefly by monitoring the loss of membrane protein -SH groups, and activities of glucose-6-phosphate dehydrogenase and alcohol dehydrogenase, the cytosolic enzymes that are particularly susceptible to oxidat...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(94)90024-8
更新日期：1994-07-01 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：:Gut microbiota is among the factors that may be involved in healthy aging. Broader and geographically spread studies on gut microbiota of centenarians can help in identifying a common signature of longevity. We identified an endogamous Indian population with high centenarian prevalence. Here, we compared the gut micro...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2019.02.001
更新日期：2019-04-01 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：:Tumor cells express NADPH oxidase-1 (NOX1) in their membrane and control NOX1-based intercellular reactive oxygen and nitrogen species (ROS/RNS)-dependent apoptosis-inducing signaling through membrane-associated catalase and superoxide dismutase. TREATMENT:of tumor cells with high concentrations of H2O2, peroxnitrite...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2017.11.005
更新日期：2018-06-01 00:00:00
abstract：:One to 24 month old rats were anesthetized with alpha-chloralose, their cerebral cortices exposed surgically and subjected in vivo to stimulation by norepinephrine (1.0mM for 5 minutes) or electrical pulses (100 pulses/s for 10 s). After microwave fixation, cortical samples were analyzed for cyclic-AMP by the Gilman m...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(75)90038-x
更新日期：1975-09-01 00:00:00
abstract：:Chronic health conditions are commonplace in older populations. The process of aging impacts many of the world's top health concerns. With the average life expectancy continuing to climb, understanding patterns of morbidity in aging populations has become progressively more important. Cancer is an age-related disease,...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2017.05.002
更新日期：2017-06-01 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：:Multimorbidity and depression are complex multifactorial conditions with major implications for older individuals, their families, and healthcare providers. In this scoping review, we aimed to 1) review findings from longitudinal epidemiological studies investigating the association between multimorbidity and depressi...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2020.111383
更新日期：2020-12-01 00:00:00
abstract：:Caloric restriction (CR) is the most effective intervention to improve health span and extend lifespan in preclinical models. This anti-aging effect of CR is related to attenuation of oxidative damage in various tissues, with divergent results in the brain. We addressed how brain oxidoreductive balance would be modula...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2019.01.002
更新日期：2019-04-01 00:00:00
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：: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：: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...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2006.01.004
更新日期：2006-05-01 00:00:00
abstract：:In yeast, increasing the copy number of the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase Sir2 extends lifespan, which can be inhibited by nicotinamide (Nam), the end-product of Sir2-mediated NAD-breakdown. Furthermore, the yeast pyrazinamidase/nicotinamidase PNC-1 can extend yeast lifespan by converti...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2007.01.004
更新日期：2007-04-01 00:00:00
abstract：:Although myocardial actomyosin ATPase specific activity determined at Ca2+ levels of 1 x 10(-3) to 1 x 10(-2) M is consistently higher in two-month old male Fischer rats than in twelve-month old individuals, this difference can be eliminated if the enzyme is assayed at lower calcium concentrations. This suggests that ...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(78)90040-4
更新日期：1978-12-01 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：:We examined physiological changes in CD5(+) B lymphocytes in mice associated with aging (from 1 or 5 to 50 weeks of age). The most predominant populations of lymphocytes among these mice were mainly CD5(-) B cells in the spleen and peritoneal cavity, and T cells in the thymus. However, in the spleen, CD5(+) B cells in...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/s0047-6374(01)00302-5
更新日期：2001-10-01 00:00:00
abstract：:The steroid hormone ecdysone influences Drosophila lifespan. Longevity is extended in mutants deficient for ecdysone synthesis or mutants of the ecdysone receptor (EcR). However, the underlying mechanisms remain unclear. Here we conditionally inactivated EcR by RNA interference or expression of dominant negative forms...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/j.mad.2009.05.004
更新日期：2009-08-01 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：: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：: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：:Amyloidosis refers to a group of protein folding diseases. Various innocuous and soluble proteins in physiological conditions polymerize to insoluble amyloid fibrils in several serious diseases, including Alzheimer's disease (AD) and prion diseases. In addition, senile amyloidosis is a form of amyloidosis in which the...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/s0047-6374(02)00098-2
更新日期：2002-11-01 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：:Hematopoietic stem cell performance and identity, crucial for homeostasis of the blood-forming system, is governed by extrinsic factors found in the bone marrow microenvironment. Communication within hematopoietic stem cell niches occurs via soluble factors or cell-to-cell contacts between niche and blood-forming cell...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章,评审
doi：10.1016/j.mad.2020.111329
更新日期：2020-10-01 00:00:00
abstract：:Previous studies from this laboratory have documented a progressive age-related decline in trophic hormone (or second messenger cAMP) stimulated corticosterone production in isolated adrenocortical cells. In the current study, we examined the possibility that the aging process exerts this effect by interfering with an...
journal_title：Mechanisms of ageing and development
pub_type： 杂志文章
doi：10.1016/0047-6374(94)90043-4
更新日期：1994-11-25 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
