Investigation on the protective action of androgen on aging and age-related diseases : from cellular senescence to frailty

• Project/Area Number: 21390220
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General internal medicine (including Psychosomatic medicine)
• Research Institution: The University of Tokyo
• Principal Investigator: AKISHITA Masahiro 東京大学, 医学部附属病院, 准教授 (00261975)
• Co-Investigator(Kenkyū-buntansha): ETO Masato 東京大学, 医学部附属病院, 特任准教授 (80282630) ; OGAWA Sumito 東京大学, 医学部附属病院, 講師 (20323579) ; OTA Hidetaka 東京大学, 医学部附属病院, 助教 (20431869)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2011: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2009: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
• Keywords: 長寿 / 老年病 / 男性ホルモン / アンドロゲン / テストステロン / DHEA

Research Abstract

This project was conducted to investigate the protective action of androgen on aging and age-related diseases. Clinical studies showed that low plasma androgen levels were associated with metabolic syndrome and atherosclerosis in middle-aged men as well as cognitive impairment, dependence and high mortality in frail elderly men and women. Basic research using cultured cells and animal models revealed the protective action of androgen on aging and the important role of NO and SIRT1 in its process.

Research Products

• [Journal Article] Hormonal effects on blood vessels (2012)
  • Author(s): Akishita M, Yu J.
  • Journal Title: Hypertens Res Volume: 35 Pages: 363-9
  • NAID: 10030644707
  • Peer Reviewed
• [Journal Article] Testosterone deficiency accelerates neuronal and vascular aging of SAMP8 mice : protective role of eNOS and SIRT1 (2012)
  • Author(s): Ota H, Akishita M, Akiyoshi T, Kahyo T, Setou M, Ogawa S, Iijima K, Eto M, Ouchi Y.
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] Testosterone deficiency accelerates neuronal and vascular aging of SAMP8 mice : protective role of eNOS and STRT1 (2012)
  • Author(s): Ota H, Akishita M, Akiyoshi T, Kahyo T, Setou M, Ogawa S, Iijima K, Eto M, Ouchi Y
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] Hormonal effects on blood vessels (2012)
  • Author(s): Akishita M, Yu J
  • Journal Title: Hypertens Res Volume: (E-pub) Issue: 4 Pages: 363-369
  • DOI: 10.1038/hr.2012.4
  • NAID: 10030644707
  • Peer Reviewed
• [Journal Article] Plasma sex hormone levels and mortality in disabled older men and women (2011)
  • Author(s): Fukai S, Akishita M, Yamada S, Ogawa S, Yamaguchi K, Kozaki K, Toba K, Ouchi Y.
  • Journal Title: Geriatr Gerontol Int Volume: 11 Pages: 196-203
  • NAID: 10029333495
  • Peer Reviewed
• [Journal Article] Association of low testosterone with metabolic syndrome and its components in middle-aged Japanese men (2010)
  • Author(s): Akishita M, Fukai S, Hashimoto M, Kameyama Y, Nomura K, Nakamura T, Ogawa S, Iijima K, Eto M, Ouchi Y.
  • Journal Title: Hypertens Res Volume: 33 Pages: 587-91
  • NAID: 10026397148
  • Peer Reviewed
• [Journal Article] Low testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors (2010)
  • Author(s): Akishita M, Hashimoto M, Ohike Y, Ogawa S, Iijima K, Eto M, Ouchi Y.
  • Journal Title: Atherosclerosis Volume: 210 Pages: 232-236
  • Peer Reviewed
• [Journal Article] Effects of testosterone in older men with mild-to-moderate cognitive impairment (2010)
  • Author(s): Fukai S, Akishita M, Yamada S, Toba K, Ouchi Y.
  • Journal Title: J Am Geriatr Soc Volume: 58 Pages: 1419-21
  • Peer Reviewed
• [Journal Article] Age-related changes in plasma androgen levels and their association with cardiovascular risk factors in male Japanese office workers (2010)
  • Author(s): Fukai S, Akishita M, Miyao M, Ishida K, Toba K, Ouchi Y.
  • Journal Title: Geriatr Gerontol Int Volume: 10 Pages: 32-9
  • NAID: 10027271554
  • Peer Reviewed
• [Journal Article] Effects of dehydroepiandrosterone supplementation on cognitive function and activities of daily living in older women with mild to moderate cognitive impairment (2010)
  • Author(s): Yamada S, Akishita M, Fukai S, Ogawa S, Yamaguchi K, Matsuyama J, Kozaki K, Toba K, Ouchi Y.
  • Journal Title: Geriatr Gerontol Int Volume: 10 Pages: 280-7
  • NAID: 10027755257
  • Peer Reviewed
• [Journal Article] Androgen receptor-dependent activation of endothelial nitric oxide synthase in vascular endothelial cells : Role of PI3-kinase/Akt pathway (2010)
  • Author(s): Yu J, Akishita M, Eto M, Ogawa S, Son BK, Kato S, Ouchi Y, Okabe T.
  • Journal Title: Endocrinology Volume: 151 Pages: 1822-8
  • Peer Reviewed
• [Journal Article] Androgen receptor-dependent transactivation of growth arrest-specific gene 6 mediates inhibitory effects of testosterone on vascular calcification (2010)
  • Author(s): Son BK, Akishita M, Iijima K, Ogawa S, Maemura K, Yu J, Takeyama K, Kato S, Eto M, Ouchi Y.
  • Journal Title: J Biol Chem Volume: 285 Pages: 7537-44
  • Peer Reviewed
• [Journal Article] Low testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors. (2010)
  • Author(s): Akishita M, Hashimoto M, Ohike Y, Ogawa S, Iijima K, Eto M, Ouchi Y.
  • Journal Title: Atherosclerosis Volume: 210 Pages: 232-236
  • Peer Reviewed
• [Journal Article] Association of low testosterone with metabolic syndrome and its components in middle-aged Japanese men. (2010)
  • Author(s): Akishita M, Fukai S, Hashimoto M, Kameyama Y, Nomura K, Nakamura T, Ogawa S, Iijima K, Eto M, Ouchi Y.
  • Journal Title: Hypertens Res Volume: 33 Pages: 587-591
  • NAID: 10026397148
  • Peer Reviewed
• [Journal Article] Effects of dehydroepiandrosterone supplementation on cognitive function and activities of daily living in older women with mild to moderate cognitive impairment. (2010)
  • Author(s): Yamada S, Akishita M, Fukai S, Ogawa S, Yamaguchi K, Matsuyama J, Kozaki K Toba K, Ouchi Y.
  • Journal Title: Geriatr Gerontol Int Volume: 10 Pages: 280-287
  • NAID: 10027755257
  • Peer Reviewed
• [Journal Article] Androgen receptor-dependent transactivation of growth arrest-specific gene 6 mediates inhibitory effects of testosterone on vascular calcification. (2010)
  • Author(s): Son BK, Akishita M, Iijima K, Ogawa S, Maemura K, Yu J, Takeyama K, Kato S, Eto M, Ouchi Y.
  • Journal Title: Journal of Biological Chemistry 285 Pages: 7537-7544
  • Peer Reviewed
• [Journal Article] Androgen receptor-dependent activation of endothelial nitric oxide synthase in vascular endothelial cells : Role of PI3-kinase/Akt pathway. (2010)
  • Author(s): Yu J, Akishita M, Eto M, Ogawa S, Son BK, Kato S, Ouchi Y, Okabe T.
  • Journal Title: Endocrinology 151 Pages: 1822-1828
  • Peer Reviewed
• [Journal Article] Association of plasma sex hormone levels with functional decline in elderly men and women (2009)
  • Author(s): Fukai S, Akishita M, Yamada S, Hama T, Ogawa S, Iijima K, Eto M, Kozaki K, Toba K, Ouchi Y.
  • Journal Title: Geriatr Gerontol Int Volume: 9 Pages: 282-9
  • NAID: 10025637981
  • Peer Reviewed
• [Journal Article] Low testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors. (2009)
  • Author(s): Akishita M, Hashimoto M, Ohike Y, Ogawa S, Iijima K, Eto M, Ouchi Y.
  • Journal Title: Atherosclerosis (Epub ahead of print)
  • Peer Reviewed
• [Presentation] ホルモンと認知症.アンドロゲンの認知機能改善作用 (2011)
  • Author(s): 秋下雅弘
  • Organizer: 日本認知症学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-12
• [Presentation] 高齢社会/アンチエイジング性ホルモンと抗老化 (2011)
  • Author(s): 秋下雅弘
  • Organizer: 日本医学会総会
  • Place of Presentation: 東京(招待講演)(Web開催)
  • Year and Date: 2011-07-19
• [Presentation] Men's Heath and Metabolism : Androgen action on vascular metabolism (2011)
  • Author(s): Akishita M
  • Organizer: 6^<th> Japan-ASEAN Conference on Men0's Health & Aging
  • Place of Presentation: Kamakura, Japan
  • Year and Date: 2011-07-01
• [Presentation] Men's Heath and Metabolism : Androgen action on vascular metabolism (2011)
  • Author(s): Akishita M
  • Organizer: 6th Japan-ASEAN Conference on Men's Health & Aging
  • Place of Presentation: Kamakura, Japan(招待講演)
  • Year and Date: 2011-07-01
• [Presentation] テストステロン医学の最前線.テストステロンと虚弱 (2011)
  • Author(s): 秋下雅弘
  • Organizer: 日本抗加齢医学会総会
  • Place of Presentation: 京都
  • Year and Date: 2011-05-29
• [Presentation] テストステロン医学の最前線.テストステロンと虚弱 (2011)
  • Author(s): 秋下雅弘
  • Organizer: 日本抗加齢医学会総会
  • Place of Presentation: 京都(招待講演)
  • Year and Date: 2011-05-29
• [Presentation] 生活習慣病におけるアンチエイジング医療:メタボ時代に最適なアンチエイジングとは?性ホルモンとメタボリックシンドローム (2011)
  • Author(s): 秋下雅弘
  • Organizer: 日本抗加齢医学会総会
  • Place of Presentation: 京都
  • Year and Date: 2011-05-27
• [Presentation] アンドロゲンの血管作用とその性差 (2011)
  • Author(s): 秋下雅弘
  • Organizer: 日本性差医学・医療学会
  • Place of Presentation: 下関
  • Year and Date: 2011-02-06
• [Presentation] 高齢社会/アンチエイジング性ホルモンと抗老化 (2011)
  • Author(s): 秋下雅弘
  • Organizer: 日本医学会総会
  • Place of Presentation: 東京
• [Presentation] 性ホルモン; Vasoprotective action of androgen and the role of androgen receptor (2010)
  • Author(s): 秋下雅弘
  • Organizer: 日本血管生物医学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-12-01
• [Presentation] テストステロンと生活習慣病;テストステロンは寿命を規定する? (2010)
  • Author(s): 秋下雅弘
  • Organizer: 日本Men's Health医学会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-27
• [Presentation] Frailty in older men-testosterone is the key for care (2010)
  • Author(s): Akishita M
  • Organizer: Men's Health World Congress
  • Place of Presentation: Nice, France
  • Year and Date: 2010-10-30
• [Presentation] Frailty in older men-testosterone is the key for care. (2010)
  • Author(s): Akishita M.
  • Organizer: Men's Health World Congress
  • Place of Presentation: Nice, France
  • Year and Date: 2010-10-30
• [Presentation] Sex hormones and atherosclerosis (2010)
  • Author(s): 秋下雅弘
  • Organizer: 日本動脈硬化学会総会・学術集会
  • Place of Presentation: 岐阜
  • Year and Date: 2010-07-16
• [Presentation] 男性ホルモン研究最前線今年の話題.アンドロゲンによるeNOS活性化機構 (2010)
  • Author(s): 秋下雅弘
  • Organizer: 日本抗加齢医学会総会
  • Place of Presentation: 京都
  • Year and Date: 2010-06-12
• [Presentation] Vasoprotective action of testosterone and the role of androgen receptor (2010)
  • Author(s): Akishita M
  • Organizer: Official Satellite Symposium of 14^<th> International Congress of Endcrinology(ICE2010): New aspects of steroids : stem cells biosynthesis and versatile actions
  • Place of Presentation: Kyoto
  • Year and Date: 2010-03-30
• [Presentation] Sex Hormone and Geriatric Medicine. (2009)
  • Author(s): 秋下雅弘(Akishita M)
  • Organizer: The 3rd International Symposium for Aging
  • Place of Presentation: Gwangju, Korea
  • Year and Date: 2009-11-28
• [Presentation] Sex Hormone and Geriatric Medicine (2009)
  • Author(s): Akishita M
  • Organizer: The 3^<rd> International Symposium for Aging
  • Place of Presentation: Gwangju, Korea
  • Year and Date: 2009-11-27
• [Presentation] 性ホルモンと老年疾患 (2009)
  • Author(s): 秋下雅弘
  • Organizer: 日本健康医学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-11-07
• [Presentation] メンズヘルス・ウィメンズヘルス男女の性ホルモンの血管保護作用 (2009)
  • Author(s): 秋下雅弘
  • Organizer: 日本抗加齢医学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-05-29
• [Book] 第2章サルコぺニアの基礎的理解第2節サルコぺニア発生のメカニズムV.アンドロゲンとサルコぺニア (2011)
  • Author(s): 江頭正人,秋下雅弘
  • Publisher: 真興交易(株)医書出版部・東京