Abstract:
:The current increase in life expectancy observed in industrialized societies underscores the need to achieve a better understanding of the aging process that could help the development of effective strategies to achieve healthy aging. This will require not only identifying genes involved in the aging process, but also understanding how their effects are modulated by environmental factors, such as dietary intake and life style. Although the human genome has been sequenced, it may be impractical to study humans or other long-lived organisms to gain a mechanistic understanding about the aging process. Thus, short-lived animal models are essential to identifying the mechanisms and genes that affect the rate and quality of aging as a first step towards identifying genetic variants in humans. In this study, we investigated gene expression changes between two strains of Drosophila (Oregon and 2b) for which quantitative trait loci (QTLs) affecting life span were identified previously. We collected males and females from both strains at young and old ages, and assessed whole genome variation in transcript abundance using Affymetrix GeneChips. We observed 8217 probe sets with detectable transcripts. A total of 2371 probe sets, representing 2220 genes, exhibited significant changes in transcript abundance with age; and 839 probe sets were differentially expressed between Oregon and 2b. We focused on the 359 probe sets (representing 354 genes) that exhibited significant changes in gene expression both with age and between strains. We used these genes to integrate the analysis of microarray gene expression data, bioinformatics, and the results of genetic mapping studies reported previously, to identify 49 candidate genes and four pathways that could potentially be responsible for regulating life span and involved in the process of aging in Drosophila and humans.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Lai CQ,Parnell LD,Lyman RF,Ordovas JM,Mackay TFdoi
10.1016/j.mad.2006.12.003subject
Has Abstractpub_date
2007-03-01 00:00:00pages
237-49issue
3eissn
0047-6374issn
1872-6216pii
S0047-6374(06)00280-6journal_volume
128pub_type
杂志文章abstract::The purpose of these studies was to analyze the role of different immune cell populations in the immune response against Trypanosoma cruzi antigens in aged mice. Mice of different ages (3 and 12 months old) were immunized i.d. with S-105 plus Bordetella pertussis as adjuvant and we compared the activities of the lymph...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(96)01719-8
更新日期:1996-07-05 00:00:00
abstract::Changes in activity of some hepatic enzymes related to UDP-glucuronic acid conjugation (UDP-glucose dehydrogenase and UDP-glucuronyl transferase) and glutathione-related enzymes (glutathione reductase and glutathione peroxidase) were investigated in male and female Wistar rats as a function of age. UDP-glucose dehydro...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(88)90084-x
更新日期:1988-08-01 00:00:00
abstract::Quantitative methods for the study of aging in single organisms of the suctorian protozoan Tokophrya infusionum are described. New cell lines are initiated by metamorphosis of a ciliated embryo to form a sessile adult. The life history of adult cells consists of a sequence of age-related stages, culminating in cessati...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(84)90095-2
更新日期:1984-08-01 00:00:00
abstract::Protein synthetic activity was determined in postmitochondrial preparations from heart, brain, kidney, liver and skeletal muscle of 5-26-month-old female C57B1/6J mice. An age-dependent decrease in the rate of protein synthesis was exhibited by all preparations except heart muscle. A 65% decrease in translational rate...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(83)90051-9
更新日期:1983-03-01 00:00:00
abstract::The observations of the loss of cholinergic function in neocortex and hippocampus in Alzheimer's disease (AD) developed the hypothesis that replacement of cholinergic function may be of therapeutic benefit to AD patients. The different approaches proposed or tested included intervention with acetylcholine (ACh) precur...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/s0047-6374(01)00310-4
更新日期:2001-11-01 00:00:00
abstract::Mortality trends in industrialized countries are characterized by declines in vascular disease (ischemic heart disease and stroke) and rises in cancers and degenerative diseases. These trends are typically analyzed by examining each disorder in isolation using the perspective of genetic and environmental influences. H...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(92)90037-e
更新日期:1992-09-01 00:00:00
abstract::Several alternative mortality models fit Swedish old-age mortality data equally well. The models build on two different concepts of the heterogeneity of individuals in a population. The first concept concerns fixed, genetic differences among individuals in their risk of death. The second concept involves acquired susc...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(94)90094-9
更新日期:1994-05-01 00:00:00
abstract::Two types of age-related cell surface changes could be demonstrated in human diploid fibroblasts with the two methods of the lectin-mediated red blood cell (RBC) adsorption assay: the fibroblast coating method (in which RBCs are adsorbed to lectin-coated fibroblasts) and the RBC coating method (in which lectin-coated ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(79)90004-6
更新日期:1979-11-01 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
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journal_title:Mechanisms of ageing and development
pub_type: 临床试验,杂志文章
doi:10.1016/0047-6374(80)90125-6
更新日期:1980-09-01 00:00:00
abstract::Formalinized Mycoplasma pulmonis was used to immunize 3 different age groups of Fischer 344 rats. A specific antibody to this antigen was detected in both saliva and lung lavage fluids and differences were noted in the elicitation of secretory antibody between the different ages of the animals. Few statistical differe...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(92)90131-v
更新日期:1992-11-01 00:00:00
abstract::With recent sequencing of the genome and development of high-density array technology, it is now possible to assess global gene expression in cells/tissues by a technique that is sensitive, quantitative, and rapid. Gene expression array technology is extremely useful in studying a complex, multigenetic process, such a...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(01)00215-9
更新日期:2001-07-31 00:00:00
abstract::The purpose of this research is to determine possible causes and mechanisms involved in the age-associated decline in mitochondrial activity. We have focused on cytochrome c oxidase because it is comprised of both nuclear and mitochondrial-encoded subunits and may provide some insight into the coordination of the two ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/s0047-6374(98)00043-8
更新日期:1998-06-15 00:00:00
abstract::There is now strong evidence implicating the generation of reactive oxygen species (ROS) and the corresponding response to oxidative stress as key factors in the pathogenesis of several human diseases including cancer, atherosclerosis, and neurodegenerative disorders, and in ageing. The carcinogenicity of oxidative st...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/j.mad.2006.01.021
更新日期:2006-05-01 00:00:00
abstract::A quantitative ultrastructural study of the posterior pituitary was undertaken. The posterior pituitary is the storage of the hormones vasopressin and oxytocin. Female C57BL/Icrfat mice which were under conditions of normal hydration were sampled at 8 and 32 months of age. There was a slight age-related decline in the...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(81)90069-5
更新日期:1981-02-01 00:00:00
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journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2015.07.001
更新日期:2015-11-01 00:00:00
abstract::A morphometric investigation has been carried out on the synaptic junctions in the cerebellar glomeruli of young-adult rats chronically deprived of vitamin E for 10 months and control animals of the same age. The following parameters were evaluated: the average length of the synapses (L), the numerical (NV) as well as...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(84)90073-3
更新日期:1984-02-01 00:00:00
abstract::Ageing of WI-38 fibroblasts in culture was used as a model in order to investigate the evolution and the alteration of the key antioxidant enzyme glutathione peroxidase. The activity of glutathione peroxidase is influenced by the presence of selenium in the culture medium and we have also shown that the specific activ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(91)90123-h
更新日期:1991-04-01 00:00:00
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journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(83)90026-x
更新日期:1983-11-01 00:00:00
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journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/j.mad.2007.10.013
更新日期:2007-11-01 00:00:00
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journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
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更新日期:2011-03-01 00:00:00
abstract::Glycosaminoglycan (GAG) distribution has been analyzed in the adhesion sites, left substratum-bound after EGTA-mediated detachment, of various human skin fibroblast populations grown in vitro in the presence (asc+) or absence (asc-) of ascorbate. Examination of these skin fibroblasts during the EGTA treatment by scann...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(85)90015-6
更新日期:1985-02-01 00:00:00
abstract::The effects of age and nutritional conditions on accumulation of autofluorescent granules in various organs and tissues of male Sprague-Dawley rats were compared morphometrically. The relative intensity of the specific fluorescence of these autofluorescent granules was similar in all tissues and cells examined. In alm...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(88)90033-4
更新日期:1988-06-01 00:00:00
abstract::Cellular and organismal decline is, in part, believed to be a consequence of oxygen and nitrogen-based reactants which persistently damage macromolecules throughout a lifetime. The resulting accumulation of damaged molecules eventually seriously compromises essential functions of cells leading to their death. Excessiv...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/s0047-6374(01)00384-0
更新日期:2002-04-30 00:00:00
abstract::DNA synthesis is a remarkably vulnerable phase in the cell cycle. In addition to introduction of errors during semi-conservative replication, the inherently labile structure of the replication fork, as well as numerous pitfalls encountered in the course of fork progression, make the normally stable double stranded mol...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/j.mad.2008.03.009
更新日期:2008-07-01 00:00:00
abstract::The occurrence of inactive enzyme molecules in a variety of tissues and animal species has been shown to be of a general nature. The levels of inactive enzyme molecules found in old animals were produced by amino acid analogs in young animals. These levels have been shown to be initially detrimental but subsequently t...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/0047-6374(79)90098-8
更新日期:1979-02-01 00:00:00
abstract::To test the validity of estimating age-related changes in rat liver nuclear RNA synthesis by following the incorporation of radioactive nucleotides into an acid-insoluble product, age-related changes in endogenous nucleotide concentration were investigated. Both the total nucleotide and the nucleoside monophosphate (N...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(80)90087-1
更新日期:1980-02-01 00:00:00
abstract::Senescence is thought to play an important role in the progressive age-related decline in tissue integrity and concomitant diseases, but not much is known about the complex interplay between upstream regulators and downstream effectors. We profiled whole genome gene expression of non-stressed and rotenone-stressed hum...
journal_title:Mechanisms of ageing and development
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.mad.2012.06.002
更新日期:2012-07-01 00:00:00
abstract::delta-Aminolevulinic acid synthase and heme oxygenase are closely functionally connected with the hepatic microsomal mixed function oxydase system. There is a wide range of changes in microsomal heme oxygenase activity, cytochrome P-450 level and mitochondrial delta-aminolevulinic acid synthase activity in rat livers ...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章
doi:10.1016/0047-6374(94)90100-7
更新日期:1994-05-01 00:00:00
abstract::Semantic distinctions between "normal" aging, "pathological" aging (or age-related disease) and "premature" aging (otherwise known as segmental progeria) potentially confound important insights into the nature of each of the complex processes. Here we review a recent, unexpected discovery: the presence of longevity-as...
journal_title:Mechanisms of ageing and development
pub_type: 杂志文章,评审
doi:10.1016/j.mad.2006.11.011
更新日期:2007-01-01 00:00:00