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Molecular and Cellular Basis of Senescence Acceleration

Research Project

Project/Area Number 09835005
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 老化(加齢)
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

HOSOKAWA Masanori  Kyoto Univ, Inst.for Frontier Med.Sci.Assoc.Prof., 再生医科学研究所, 助教授 (00127135)

Co-Investigator(Kenkyū-buntansha) HIGUCHI Keiichi  Shinshu Univ.Faculty of Med.Professor, 信州大学・医学部, 教授 (20173156)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsSenescence Acceleration / Genome Typing / Animal Model / Mice / Senile Osteopsrosis / Cell Culture / Oxidative Stress / Mitochondria / 大動脈 / 多倍体化
Research Abstract

The chromosomes of accelerated senescence-prone, short lived, 9 strains of SAMP and accelerated senescence-resistant, long lived, 3 strains of SAMR were typed with microsatellite markers. Comparison of the distribution of loci in the SAMP and SAMR strains revealed notable differences in the Chrs 4, 14, 16 and 17. This indicted that some of these chromosomal sites might contain the genes responsible for senescence acceleration.
The whole genome scan for quantitative trait Ioci (QTLs) specifying peak bone mass was performed with the F2 intercrosses of SAMP6, senile osteoporosis model and SAMP2 with high peak bone mass. QTLs were identified on Chrs 11, 13 and X.
Accelerated changes of in vitro aging were examined in fibroblast-like cells isolated from the dorsal dermis of newborn SAMP11 (accelerated senescence-prone, short lived) mice and were compared to the cell lines from SAMR1 (accelerated senescence-resistant, long lived) mice. The changes occurred more rapidly and at earlier population doublings in the cell lines from the SAMP11 mice. Aminoguanidine supplementation in this culture reduced the lipid peroxidation and delayed the senescence/crisis.
The redox state and oxidative phosphorylation of the brain mitochondria from 2-month-old SAMP8 mice, an age-associated neurodegenerative model were investigated. The SAMP8 brain mitochondria demonstrated higher redox state and a higher activity of mitochondrial respiration with lower respiration control ratio. This indicated that an inefficient hyperactive state can exist in the mitochondrial electron transport system before the age-associated mitochondrial dysfunction develops.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (53 results)

All Other

All Publications (53 results)

  • [Publications] Hosokawa, M.: "In vitro study of the mechanisms of senescence acceleration" Expenmental Gerontology. 32. 197-204 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.: "Age-related changes in the brain transfer of blood-borne horse radish Peroxidase in the hippocampus of Senescence-accelerated Mouse(SAM)" Acta Neuro pathologica. 93. 233-240 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi, K.: "Accurculation of pro-apolipoprotein A-II in mouse senile amyloidosis" Biochemical Journal. 325. 653-659 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.: "Cell death in the inner ear associated with aging is apoptosis?" Brain Research. 747. 147-150 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosono, M.: "Interventions of senescence in SAM mice" Journal of Anti-Aging Medicine. 1. 27-37 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi, K.: "Fibrilization in mouse senile amyloidosis is fibril conformation-dependent" Laboratory Investigation. 78. 1535-1542 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.: "Accelerated accumulation of somatic mutations in the Senescence-accelerated mouse" Nature Genetics. 19. 116-117 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.: "Accelerated aging of dermal fibroblast-like cells from the Senescence-Accelerated Mouse(SAM):Acceleration of changes in DNA ploidy" Journal of Gerontology. 53A. B11-B17 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.: "A morphological and morphometrical study of the retina in aging SAM mice" Ophthalmic Research. 30. 172-179 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.: "Age-related changes in blood pressure in Senescence-accelerated mouse(SAM). Aged SAMPL mice manifested hypertensive vascular diseases" Laboratory Animal Sciences. 48. 97-104 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.: "Spontaneous and artificial lesions of magno cellular reticular formation of brain stem deteriorate avoidance learning in senescence-accelerated mouse, SAM" Brain Research. 791. 90-98 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.: "An early stage mechanism of the age-associated mitochondrial dysfunction in the brain of SAM98 mice : an age-associated neurodegeneration animal model" Neuroscience Letters. 254. 69-72 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.: "Ultrastructural and permeability features of microvessels in the olfactory bulbs of SAM mice" Acta Neuropathologica. 96. 261-270 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.: "Identification of quantitative trait loci that control low peak bone mass using a spontaneously osteo porotic mouse strain SAM96" Mammalian Genome. 10. 81-87 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi, K.: "Genetic typing of the Senescence-accelerated Mouse(SMA) strains with microsatellite markers" Mammalian Genome. (印刷中). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.: "Aminoguanidine supplementation delays the onset of senescence in vitro in dermal fibroblast-like cells form Senescence-accelerated mice" Journal of Gerontology. (印刷中). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M., et al.: "In vitro study of the mechanisms of senescence acceleration" Exp.Gerontol. 32. 197-204 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.et al.: "Age-related chenges in the brain transfer of blood borne horseradish peroxidase in the hippocampus of Senescence-accelerated mouse (SAM)" Acta Neuropathol.93. 233-240 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi, K., et al.: "Accumulation of pro-apolipoprotein A-II in mouse senile amyloidosis" Biochemical Journal. 325. 653-659 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.et al.: "Cell death in the inner ear associated with aging is apoptosis?" Brain Research. 747. 147-150 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi, K.et al.: "Fibrilization in mouse senile amyloidosis is fibril conformation-dependent" Lab.Invest.78. 1535-1542

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.et al.: "Accelertaed accumulation of somatic mutations in the Senescence-accelerated mouse" Nature Genetics. 19. 116-117 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.et al.: "Accelerated aging of dermal fibroblast-like cells from the Senescence-accelerated Mouse (SAM) : Acceleration of changes in DNA ploidy associated with in vitro aging" J.Gerontology. 53A. B11-B17 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.et al.: "Interventions of senescence in SAM mice" J.Anti-Aging Med.1. 27-37 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.et al.: "A morphological and morphometrical study of the retina in aging SAM mice" Ophthalmic Res.30. 172-179 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.et al.: "Age-related changes in blood pressure in Senescence-accelertaed mouse(SAM). Aged SAMP1 mice manifested hypertensive vascular disease" Lab.Animal Sci.48. 97-104 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.et al.: "Spontaneous and arti-ficial lesions of magnocellular reticular formation of brain stem deteriolate avoidance learning in senescence-accelerated mouse SAM" Brain Res.791. 90-98 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.et al.: "An early stage mechanisms of the age-associated mitochondrial dysfunction in the brain of SAMP8 mice : an age-associated neurodegeneration animal model" Neurosci.Letters. 254. 69-72 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.et al.: "Ultrastructural and permeability features of microvessels in the olfactoty bulbs of SAM mice" Acta Neuropatho1.96. 261-270 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.et al.: "Identification of quanti-tative trait loci that control low peak bone mass using a spontaneously osteoporotic mouse strain SAMP6" Mammalian Genome. 10. 81-87 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi, K.et al.: "Genetic typing of the Senescence-accelerated Mouse (SAM) strains with microsatellite markers" Mammalian Genome. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa, M.et al.: "Aminoguanidine supple-mentation delays the onset of senescence in vitro in dermal fibroblast-like cells from Senescence-accelerated mice" J.Gerontology. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fujisawa,H.: "Aminoguanidine supplementation delays the onset of senescence in vitro in dermal fibroblast-like cells from senescence-accelerated mice." Journal of Gerontology. (発行予定). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takubo,Y.: "Age-associated changes in elastin and collaqeu content and the proportion of type I and III collagen in the lungs of mice" Experimental Gerontology. (発行予定). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takeda,S.: "Expression of c-fos gene induced by parathyroid hormone in bones of SAMP6 mice,a murine model for scnile osteonorosis" Mechanisms of Ageing and Development. (発行予定). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Xia,C.: "Genetic typing of the Senescence-Accelerated Mouse (SAM) strains with micro sate llite markers" Mammalian Genome. (発行予定). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimizu,M.: "Identification of quantitative trait loci that control low peak bone mass using a spontaneously ostoporotic mouse strain SAM6." Mammalian Genome. 10. 81-87 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Umezawa,M.: "High-linoleate and high-α-linolenate diet aflect learning ability and natural hebavior in SAMRI mice" Journal of Nutrition. 129. 431-437 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ueno,M.: "Ultrastructural and permeability Peatures of microvesselis in the oltactory bulbs of SAM mice" Acta Neuropathologica. 96. 261-270 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishikawa,T.: "An early stage mecharism of the age-associated mitochondrial disfunction in the brain of SAMP8 mice : on age-associated neuro degeneration anisal model" Neurosience Letters. 254. 69-72 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yagi,H.: "Spantaneous and artificial ksions of magno cellular reticular formation of brain stem deteriorate avoidance learning in serescence-accelerated mouce SAM" Brain Research. 791. 90-98 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Han,J.X.: "Age-related changes in blood pressure in Senescence-Accelerated Mouse (SAM) Ased SAMP1 mice nonifested hyper tensive rescular disease" Laboratory Animal Sciences. 48. 97-104 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shoji,M.: "A morphological and morpohmetrical study of the retina in aging SAM mice" Ophthalmic Research. 30. 172-179 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fujisawa,H.: "Accelerated aging of dermal fibroblast-like cells from the Seneccence-Acceleratal Mouce (SAM) : Acceleration of changes in DNA aloidy associated with in vitro aging" Journal of Gerontology. 53A. B11-B17 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hosokawa,M.: "Interventions of senescence in SAM mice." Journal of Anti-Aging Medicine. 1. 27-37 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Higuchi,K.: "Fibrilization in mouse senile amyloidosis is fibril conformation-dependust" Labratory Investigation. 78. 1535-1542 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Odagiri,Y.: "Accelevated accumulation of somatic mutations in the senescence accele rated mouse" Nature Genetics. 19. 116-117 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hosokawa,M.: "Interventions of senescencein SAM Mice" Journal of Anti-Aging Medicine. 1. 27-37 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujisawa,H.: "Accelerated aging of dermal fibroblast-like cells from Senescece-Accderated Mouse(SAM):Acceloation of changes in DNA ploidy asseciated with in vitra ceyulan aging" Journal of Gerontology. 53A. B11-B17 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hosokawa,M.: "In vitro study of the mechanisms of senescence acceleration" Experimental Gerontology. 32. 197-204 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ueno,M.: "Age-related changes in the brain transfer of blood-borne horseradish goroxidase in the hippocampus of Senescence-Acceleated Mouse(SAM)" Acta Neuropathologica. 93. 233-240 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Higuchi,K.: "Accumulation of pro:apol:poprotein A-II in mouse senile amyloid fibrils" Biochemical Journal. 325. 653-659 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Usami,S.: "Cell death in the inner ear associated with aging is apoptosis?" Brain Research. 747. 147-150 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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