• Title/Summary/Keyword: longevity gene

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Growth signaling and longevity in mouse models

  • Kim, Seung-Soo;Lee, Cheol-Koo
    • BMB Reports
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    • v.52 no.1
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    • pp.70-85
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    • 2019
  • Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) extends the lifespan of various species. So far, several longevity mouse models have been developed containing mutations related to growth signaling deficiency by targeting growth hormone (GH), IGF1, IGF1 receptor, insulin receptor, and insulin receptor substrate. In addition, p70 ribosomal protein S6 kinase 1 (S6K1) knockout leads to lifespan extension. S6K1 encodes an important kinase in the regulation of cell growth. S6K1 is regulated by mechanistic target of rapamycin (mTOR) complex 1. The v-myc myelocytomatosis viral oncogene homolog (MYC)-deficient mice also exhibits a longevity phenotype. The gene expression profiles of these mice models have been measured to identify their longevity mechanisms. Here, we summarize our knowledge of long-lived mouse models related to growth and discuss phenotypic characteristics, including organ-specific gene expression patterns.

Animal Models for the IGF-1 Signal System in Longevity (장수와 관련된 IGF-1 신호 시스템을 연구하기 위한 동물 모델)

  • Kwak, Inseok
    • Journal of Life Science
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    • v.22 no.10
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    • pp.1428-1433
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    • 2012
  • Longevity is an exciting but difficult subject to study because it is determined by complex processes that require the coordinated action of several genetic factors as well as physiological and environmental influences. Genetic approaches have been applied to animal models to identify the molecular mechanism responsible for longevity. Several experimental model organisms obtained over the last decades suggest that the complete deletion of a single gene by gene targeting has proven to be an invaluable tool for the discovery of the mechanisms underlying longevity. The first discovery of long-lived mutants came from Caenorhabditis elegans research, which identified the insulin/IGF-1 pathway as responsible for longevity in this worm. IGF-1 is a multifunctional polypeptide that has sequence similarity to insulin and is involved in normal growth and development of cells. Several factors in the IGF-1 system have since been studied by gene targeting in the control of longevity in lower species, including nematode and fruit fly. In addition, significant progress has been made using mice models to extend the lifespan by targeted mutations that interfere with growth hormone/IGF-1 and IGF-1 signaling cascades. A recent finding that IGF-1 is involved in aging in mice was achieved by using liver-specific knockout mutant mice, and this clearly demonstrated that the IGF-1 signal pathway can extend the lifespan in both invertebrates and vertebrate models. Although the underlying molecular mechanisms for the control of longevity are not fully understood, it is widely accepted that reduced IGF-1 signaling plays an important role in the control of aging and longevity. Several genes involved in the IGF-1 signaling system are reviewed in relation to longevity in genetically modified mice models.

Multi-level remodeling of transcriptional landscapes in aging and longevity

  • Lai, Rochelle W.;Lu, Ryan;Danthi, Prakroothi S.;Bravo, Juan I.;Goumba, Alexandre;Sampathkumar, Nirmal Kumar;Benayoun, Berenice A.
    • BMB Reports
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    • v.52 no.1
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    • pp.86-108
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    • 2019
  • In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and gene expression has been observed to be deregulated with aging. In this review, we discuss the current knowledge on the transcriptional alterations that have been described to occur with age in metazoans. First, we discuss age-related transcriptional changes in protein-coding genes, the expected functional impact of such changes, and how known pro-longevity interventions impact these changes. Second, we discuss the changes and impact of emerging aspects of transcription in aging, including age-related changes in splicing, lncRNAs and circRNAs. Third, we discuss the changes and potential impact of transcription of transposable elements with aging. Fourth, we highlight small ncRNAs and their potential impact on the regulation of aging phenotypes. Understanding the aging transcriptome will be key to identify important regulatory targets, and ultimately slow-down or reverse aging and extend healthy lifespan in humans.

Longevity Genes: Insights from Calorie Restriction and Genetic Longevity Models

  • Shimokawa, Isao;Chiba, Takuya;Yamaza, Haruyoshi;Komatsu, Toshimitsu
    • Molecules and Cells
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    • v.26 no.5
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    • pp.427-435
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    • 2008
  • In this review, we discuss the genes and the related signal pathways that regulate aging and longevity by reviewing recent findings of genetic longevity models in rodents in reference to findings with lower organisms. We also paid special attention to the genes and signals mediating the effects of calorie restriction (CR), a powerful intervention that slows the aging process and extends the lifespan in a range of organisms. An evolutionary view emphasizes the roles of nutrient-sensing and neuroendocrine adaptation to food shortage as the mechanisms underlying the effects of CR. Genetic and non-genetic interventions without CR suggest a role for single or combined hormonal signals that partly mediate the effect of CR. Longevity genes fall into two categories, genes relevant to nutrient-sensing systems and those associated with mitochondrial function or redox regulation. In mammals, disrupted or reduced growth hormone (GH)-insulin-like growth factor (IGF)-1 signaling robustly favors longevity. CR also suppresses the GH-IGF-1 axis, indicating the importance of this signal pathway. Surprisingly, there are very few longevity models to evaluate the enhanced anti-oxidative mechanism, while there is substantial evidence supporting the oxidative stress and damage theory of aging. Either increased or reduced mitochondrial function may extend the lifespan. The role of redox regulation and mitochondrial function in CR remains to be elucidated.

Anti-Apoptosis Engineering Using a Gene of Bombyx mori

  • Kim, Eun-Jeong;Park, Tae-Hyeon
    • 한국생물공학회:학술대회논문집
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    • 2002.04a
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    • pp.62-65
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    • 2002
  • We have previously shown that the addition of silkworm hemolymph to a culture medium increases the longevity of insect and mammalian cells by inhibiting apoptosis. This indicates that the component which inhibits apoptosis is contained in the silkworm hemolymph, The apoptosis-inhibiting component was isolated from silkwonn hemolymph and characterized in our previous study. A database search using the N-terminal amino acid sequence of this component as a template resulted in a 95% homology with a low molecular weight lipoprotein, the so called ’30K protein' of unknown function. In this study, the 30K protein gene was expressed in mammalian and insect cells to confirm the apoptosis-inhibiting effect. The overexpression of 30K protein in mammalian cell inhibited the staurosporin-induced apoptosis by the prevention of the activation of caspase 3. Using an Autographa californicanuclear polyhedrosis virus (AcNPV) system, the 30K protein was overexpressed also in insect cells. The expression of the 30K protein increased the longevity of baculovirus-infected insect cells by inhibiting apoptosis. These results suggest that the 30K protein is a novel anti-apoptotic protein.

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Pollen-Mediated Gene Flow between Glufosinate Ammonium-Tolerant GM and Non-GM Rice

  • Lee, Seung-Yeob;Kim, Min-Soo;Kim, Hyo-Jin;Ahn, Jeong-Ho;Baek, So-Hyeon;Shin, Woon-Chul;Kim, Hyun-Soon
    • Journal of Plant Biotechnology
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    • v.34 no.1
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    • pp.47-53
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    • 2007
  • To assess the risk of genetically modified (GM) rice on the agricultural ecosystem, agronomic characteristics, pollen longevity and outcrossing rate between GM (Iksan 483 and Milyang 204) and non-GM (their wild types and female parents) varieties were investigated using the bar gene as a tracer marker in paddy field. The agronomic characteristics of two GM rice were similar to their female-parents (non-GM rice) except heading date and 1,000 grain weight of Iksan 483, and they did not show a difference by the introgression of the bar gene as the genetic traits of rice varieties. Pollen viability was more than 90% just after shedding, and it was rapidly decreased below 50% at 5 minutes after shedding both GM and non-GM varieties. The Pollen longevity was lost after 30 minutes of anthesis. When the distance of gene flow from GM to non-GM rice detected to 6 m from the edge of GM rice plant, the maximum distance of pollen dispersal was 4.5m and 3.9m in Iksan 483 and Milyang 204, respectively, and that was increased in order of west, south, east, and north to the dominant wind direction, west-south. Mean outcrossing rate was very low as 0.003 and 0.001% within 1.5 m from the edge of Iksan 483 and Milyang 204, and the GM hybrids by the pollen dispersal did not detected over 4.5 m from the edge of GM rice plant. The results may help to establish the strategy which reduce the risk of pollen-mediated gene flow between GM and non-GM rice.

Dormancy Associated Weedy Risk of the F1 Hybrid Resulted from Gene Flow from Oilseed Rape to Mustard (유채로부터 갓으로 유전자이동에 의한 교잡종의 휴면에 따른 잡초화 가능성)

  • Lim, Yeonhwa;Yook, Min-Jung;Zhang, Chuan-Jie;Nah, Gyoungju;Park, Suhyoung;Kim, Do-Soon
    • Weed & Turfgrass Science
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    • v.4 no.1
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    • pp.35-43
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    • 2015
  • To assess the dormancy associated weedy risk of the F1 hybrid generated by hybridization between Brassica juncea (maternal) and Brassica napus (paternal), seed germination, dormancy and longevity were examined sequentially after seed harvest. The F1 hybrids exhibited the intermediate characteristics of their parents in seed germination and dormancy with relatively high dormancy rate of 41.1%. In summer, F1 hybrid seeds buried in the 3 cm soil exhibited greater viability (52.4%) than those in the soil surface with greater seed longevity (74.6%) than its maternal (63.3%) and paternal (33.7%) parents at 100 days of over-summering in soil. In winter, F1 seeds buried in the soil surface were more viable than those in the 3 cm soil with greater seed longevity (83.5%) than its maternal (39.0%) and paternal (71.7%) parents at 100 days of over-wintering in soil. Therefore, it is concluded that F1 hybrid resulted from gene flow from OSR to mustard has high seed dormancy and longevity during summer and winter, suggesting its weedy risk potential. Further studies are required to examine the reproductivity and fitness cost of F1 hybrid to make a clearer conclusion of its weedy risk.

General Characteristics and Life Span of Silkworm Moth According to Varieties, Bombyx mori. (누에 품종별 누에나방의 수명과 실용형질)

  • 강필돈;류강선;김계명;손봉희;촌상소웅;손흥대
    • Journal of Sericultural and Entomological Science
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    • v.41 no.3
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    • pp.154-166
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    • 1999
  • General characteristics and life span of silkworm moth were investigated amongst 277 gene resources preserved and maintained in Korea. Silkworm varieties were classified according to the commercial characteristics and the viability of tested varieties. There were significant differences among the eight different commercial characteristics of silkworm such as whole larval period, duration of 5th instar, pupal body weight, single cocoon weight, cocoon shell weight, cocoon shell ratio, cocoon yield and longevity, Tropical race showed the longest life span among the other five geographical races, and followed by Japanese, European, Chinese and Korean race in order. In the longevity of each variety, Daizo(sdi) showed the shortest life span with 4.3days, and J037 was the longest as 16.0 days. Average longevity of female was 11.1 days as showed 3.0 days longer than that of male which was 8.2 days. Total average longevity of the whole varieties was 9.7days. In the correlation between the longevity and commercial characteristics, there was a tendency that the commercial characteristics became better when the life span was longer. According to the result of Complete Linkage Cluster Analysis, the genetic resources of 277 silkworm varieties classified into 5 groups such as “Group I”for short life span with low cocoon yielding “Group II”for middle life span with middle cocoon yielding,“Group III”for the shortest life span with low cocoon yielding, “Group IV”for high pupation rate and the highest cocoon yielding with comparatively long life span, and “Group V”for the longest life span with comparatively high cocoon yielding.

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Changes in the Fitness of Brown Planthopper, Nilapawata lugens Stal (Homoptera: Delphacidae) to Several Resistant Rice Varieties after Multi-generational Selection (누대도태에 의한 벼멸구의 품종적응성의 변화)

  • 송유한;황인철;김진호
    • Korean journal of applied entomology
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    • v.41 no.2
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    • pp.113-121
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    • 2002
  • This study investigated the changes in the fitness of brown planthopper, NilapaHata lugens, to several rice varieties with different resistance background, after multi-generational selection on a resistant rice variety. A susceptible strain of brown planthopper (Dongjin-5) had been reared on the Chungchungbyeo with Bph1 resistance gene for three generations (Chungchung-G3) and six generations (Chungchung-G6), then the fitness change was evaluated by measuring their longevity, fecundity, preferences, and survivorships on the varieties with various background of resistance. After being selected three to six generations on Chungchungbyeo, feeding preference, adult longevity, and fecundity increased, where as nymphal period reduced when they were reared on various varieties with Bph1 gene. The egg Periods were not much different among the varieties fed on, except for the Chungchung-G6 on the rice varieties of Milyang63 (bph2 gene) and Gayabyeo (Bph1+bph2 gene). These results suggest that the susecptible Donajin-5 (Biotype-1) can be easily converted to a resistant biotype-2 capable of overcoming the resistant varieties with Bph 1 gene.

Radiation Hormesis: Incredible or Inevitable\ulcorner

  • Ducoff, Howard-S
    • Animal cells and systems
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    • v.6 no.3
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    • pp.187-193
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    • 2002
  • It has long been recognized that exposure to low levels of toxic chemicals could have beneficial effects, such as increased resistance to related chemicals or stimulation of growth or development. The notion of radiation hormesis, that exposure to low levels of ionizing radiation could produce beneficial effects, developed seriously in the late 1950’s, and was, to most radiation scientists, incredible. This was due in pan to the then prevailing ideas of radiobiological mechanisms, in part to the sweeping generalizations made by the leading proponents of the radiation hormesis concept, and in pan to the many failures to confirm reports of beneficial effects. More recent understanding of the mechanisms of radiation damage and repair, and discoveries of induction of gene expression by radiation and other genotoxic agents [the adaptive response] make it seem inevitable that under suitable conditions, irradiation will produce beneficial effects.