Differential Gene Expression and Aging

Seroude, Laurent

doi:10.1100/tsw.2002.135

Cited by 14 publications

(6 citation statements)

References 135 publications

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“…Aging is a fundamental biological process that has distinct phenotypical, physiological and molecular level characteristics. The gene expression level change hypothesis of aging is one of the principal theories of age-associated changes in cellular functions in many tissues, including the brain [ 30 , 56 , 61 ]. Accordingly, the functional genomics approach is one of the useful ways for describing some of the molecular characteristics of neuronal changes underlying normal aging and neurodegeneration [ 30 , 62 - 65 ].…”

Section: Discussionmentioning

confidence: 99%

Age-associated bidirectional modulation of gene expression in single identified R15 neuron of Aplysia

et al. 2013

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BackgroundDespite the advances in our understanding of aging-associated behavioral decline, relatively little is known about how aging affects neural circuits that regulate specific behaviors, particularly the expression of genes in specific neural circuits during aging. We have addressed this by exploring a peptidergic neuron R15, an identified neuron of the marine snail Aplysia californica. R15 is implicated in reproduction and osmoregulation and responds to neurotransmitters such as acetylcholine, serotonin and glutamate and is characterized by its action potential bursts.ResultsWe examined changes in gene expression in R15 neurons during aging by microarray analyses of RNAs from two different age groups, mature and old animals. Specifically we find that 1083 ESTs are differentially regulated in mature and old R15 neurons. Bioinformatics analyses of these genes have identified specific biological pathways that are up or downregulated in mature and old neurons. Comparison with human signaling networks using pathway analyses have identified three major networks [(1) cell signaling, cell morphology, and skeletal muscular system development (2) cell death and survival, cellular function maintenance and embryonic development and (3) neurological diseases, developmental and hereditary disorders] altered in old R15 neurons. Furthermore, qPCR analysis of single R15 neurons to quantify expression levels of candidate regulators involved in transcription (CREB1) and translation (S6K) showed that aging is associated with a decrease in expression of these regulators, and similar analysis in three other neurons (L7, L11 and R2) showed that gene expression change during aging could be bidirectional.ConclusionsWe find that aging is associated with bidirectional changes in gene expression. Detailed bioinformatics analyses and human homolog searches have identified specific biological processes and human-relevant signaling pathways in R15 that are affected during aging. Evaluation of gene expression changes in different neurons suggests specific transcriptomic signature of single neurons during aging.

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Section: Discussionmentioning

confidence: 99%

Age-associated bidirectional modulation of gene expression in single identified R15 neuron of Aplysia

et al. 2013

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“…However, genes impacting TRY–KYN pathways have not been considered among genetic pathways influencing longevity in Drosophila (Seroude 2002). There is only one study evaluating the life span of Drosophila mutants with impaired kynurenine pathway of TRY metabolism (Kamyshev 1980).…”

Section: Introductionmentioning

confidence: 99%

The extended life span of Drosophila melanogaster eye-color (white and vermilion) mutants with impaired formation of kynurenine

Oxenkrug

2009

J Neural Transm

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Animal and human studies suggest that aging is associated with increased formation of kynurenine (KYN) from tryptophan (TRY). The rate-limiting factors of TRY–KYN metabolism are transmembrane transport of TRY, and activity of enzyme, TRY 2,3-dioxygenase (TDO2). Eye-color mutants, white (w1118) (impaired TRY transport) and vermilion (v48a and v2) (deficient TDO activity), were compared with wild-type Oregon-R (Ore-R) strain of Drosophila melanogaster. Female 1-day-old adult flies maintained on a standard medium, and acclimatized to 12-h light:12-h dark cycle were collected, and then regularly transferred to fresh medium every 3–4 days. The number of dead flies was recorded at the time of transfer. Forty flies were studied in each experimental group. The life span of w1118 (mean = 45.5 days), and v48a (mean = 47.6 days) and v2 (mean = 43.8 days), were significantly longer than of wild-type Ore-R flies (27.1 days) (p < 0.001, Logrank test). There were no differences in life span between w1118 and v48a and v2 mutants. Present results suggest that prolongation of life span may be associated with slow rate of KYN formation from TRY.

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“…Genes and environment play roles in aging (Seroude 2002). Identification of genes regulating longevity in yeast (Childress et al 1996;Sun and Tower 1999), Drosophila (Orr et al 2003) and C. elegans (Friedman and Johnson 1988;Felkai et al 1999) have been widely reported.…”

Section: Introductionmentioning

confidence: 99%

Age-dependent differential expression and activity of rat liver cytosolic inorganic pyrophosphatase gene

et al. 2007

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Besides epigenetic factors, the genetic make-up and differential gene expression not only determines aging and disease susceptibility but also the functional activity of cells in an individual. Analysis of a variety of mammalian tissues revealed that the age-associated differentially expressed genes mainly belong to inflammation, stress, and metabolism. Intracellular PPi is a by-product of multiple biosynthetic reactions and its hydrolysis by cytosolic inorganic pyrophosphatase (iPPase) has long been considered as an important homeostatic mechanism favoring biosynthesis. In this paper we report an age-associated increase ( approximately 2-fold) in the expression of rat liver cytosolic iPPase gene by differential display PCR and northern blot analysis. Expression profiling of iPPase by RNA slot blot analysis in several other tissues revealed no significant change with aging. A comparative spectrophotometric and in-gel analysis of iPPase activity in whole cell lysate (WCL) of liver, brain, skeletal muscle, heart, spleen and kidney exhibited that liver of old rats (24 months ) has approximately 2-fold more activity than the adult (4 months) ones and also its activity is highest among the tissues. The specificity of iPPase activity in the spectrophotometric assay and in-gel analysis was confirmed by specific iPPase inhibitors like CaCl(2) and NaF.

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Differential Gene Expression and Aging

Cited by 14 publications

References 135 publications

Age-associated bidirectional modulation of gene expression in single identified R15 neuron of Aplysia

Age-associated bidirectional modulation of gene expression in single identified R15 neuron of Aplysia

The extended life span of Drosophila melanogaster eye-color (white and vermilion) mutants with impaired formation of kynurenine

Age-dependent differential expression and activity of rat liver cytosolic inorganic pyrophosphatase gene

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