1998 Fiscal Year Annual Research Report

老化過程の促進機構の分子細胞生物学的基盤-モデル動物を用いた研究-

Research Project

Project/Area Number	09835005
Research Institution	KYOTO UNIVERSITY
Principal Investigator	細川昌則京都大学, 再生医科学研究所, 助教授 (00127135)
Co-Investigator(Kenkyū-buntansha)	樋口京一信州大学, 医学部, 教授 (20173156)
Keywords	老化促進 / モデル動物 / マウス / 酸化ストレス / 培養細胞 / ミトコンドリア
Research Abstract	老化促進を示し短寿命のSAMP11マウス、及び遺伝的に近縁で寿命の長いSAMR1マウスの新生仔皮膚より線維芽細胞をトリプシンで単離し、10%牛胎仔血清添加DMEM培地にて週1回定期的に継代培養した。さらにジアミンオキシダーゼ阻害剤のアミノグアニジンを添加群(2,4mM)を作製した。試験管内加齢のパラメターとして細胞形態、分裂細胞の染色体数、定常期細胞の核DNA量を測定した。試験管内加齢に伴い、2倍体細胞が減少し、多倍体細胞が増加した。細胞の不死化に伴い、低4倍体細胞が主要細胞になった。この変化はSAMP11マウス、SAMR1マウス由来細胞に共に認められたが、SAMP11マウス由来細胞では急速に、少ない分裂回数で起こり、試験管内加齢が促進していることが示された。マウス細胞の培養系でアミノアルデヒドや過酸化水素を産生するアミンオキシダーゼの阻害剤であるアミノグアニジンの添加はSAMP11マウス初代培養細胞の過酸化脂質を減少させ、上記の試験管内加齢変化を遅延させた。加齢に伴い脳機能障害をきたすSAMP8マウスでは若齢より脳組織ミトコンドリア画分において、複合体2より下流での酸化的リン酸化機能の亢進、呼吸調節率の低下、高還元状態が示され、ミトコンドリア機能の非効率的機能亢進状態にあると考えられた。これらの事実はSAMPマウスの老化の促進の機構として、高酸化ストレスによる細胞機能低下が重要な役割を果たしていることを示している。

Research Products
(15 results)

All Other

All Publications (15 results)

[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)
[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)
[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)
[Publications] Xia,C.: "Genetic typing of the Senescence-Accelerated Mouse (SAM) strains with micro sate llite markers" Mammalian Genome. (発行予定). (1999)
[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)
[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)
[Publications] Ueno,M.: "Ultrastructural and permeability Peatures of microvesselis in the oltactory bulbs of SAM mice" Acta Neuropathologica. 96. 261-270 (1998)
[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)
[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)
[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)
[Publications] Shoji,M.: "A morphological and morpohmetrical study of the retina in aging SAM mice" Ophthalmic Research. 30. 172-179 (1998)
[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)
[Publications] Hosokawa,M.: "Interventions of senescence in SAM mice." Journal of Anti-Aging Medicine. 1. 27-37 (1998)
[Publications] Higuchi,K.: "Fibrilization in mouse senile amyloidosis is fibril conformation-dependust" Labratory Investigation. 78. 1535-1542 (1998)
[Publications] Odagiri,Y.: "Accelevated accumulation of somatic mutations in the senescence accele rated mouse" Nature Genetics. 19. 116-117 (1998)

1998 Fiscal Year Annual Research Report

老化過程の促進機構の分子細胞生物学的基盤-モデル動物を用いた研究-

Principal Investigator

細川 昌則 京都大学, 再生医科学研究所, 助教授 (00127135)

Research Products

[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)

[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)

[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)

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

[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)

[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)

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

[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)

[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)

[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)

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

[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)

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

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

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

細川昌則京都大学, 再生医科学研究所, 助教授 (00127135)