Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging

Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transi...
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Autor*in:	Jonathan B. Lin [verfasserIn] Abdoulaye Sene [verfasserIn] Andrea Santeford [verfasserIn] Hideji Fujiwara [verfasserIn] Rohini Sidhu [verfasserIn] Marianne M. Ligon [verfasserIn] Vikram A. Shankar [verfasserIn] Norimitsu Ban [verfasserIn] Indira U. Mysorekar [verfasserIn] Daniel S. Ory [verfasserIn] Rajendra S. Apte [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Übergeordnetes Werk:	In: EBioMedicine - Elsevier, 2015, 32(2018), Seite 9-20
Übergeordnetes Werk:	volume:32 ; year:2018 ; pages:9-20

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.ebiom.2018.05.035

Katalog-ID:	DOAJ040202143

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allfields	10.1016/j.ebiom.2018.05.035 doi (DE-627)DOAJ040202143 (DE-599)DOAJaffa62f8204a49bdbf413e70b5b10010 DE-627 ger DE-627 rakwb eng R5-920 Jonathan B. Lin verfasserin aut Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. Here, we show that despite their frequent self-renewal, macrophages from old mice exhibited numerous signs of aging, such as impaired oxidative respiration. Transcriptomic profiling of aged murine macrophages revealed dysregulation of diverse cellular pathways, especially in cholesterol homeostasis, that manifested in altered oxysterol signatures. Although the levels of numerous oxysterols in human peripheral blood mononuclear cells and plasma exhibited age-associated changes, plasma 24-hydroxycholesterol levels were specifically associated with AMD. These novel findings demonstrate that oxysterol levels can discriminate disease from physiologic aging. Furthermore, modulation of cholesterol homeostasis may be a novel strategy for treating age-associated diseases in which macrophage aging is pathogenic. Keywords: Age-related macular degeneration, Aging, Lipids, Cholesterol Medicine R Medicine (General) Abdoulaye Sene verfasserin aut Andrea Santeford verfasserin aut Hideji Fujiwara verfasserin aut Rohini Sidhu verfasserin aut Marianne M. Ligon verfasserin aut Vikram A. Shankar verfasserin aut Norimitsu Ban verfasserin aut Indira U. Mysorekar verfasserin aut Daniel S. Ory verfasserin aut Rajendra S. Apte verfasserin aut In EBioMedicine Elsevier, 2015 32(2018), Seite 9-20 (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:32 year:2018 pages:9-20 https://doi.org/10.1016/j.ebiom.2018.05.035 kostenfrei https://doaj.org/article/affa62f8204a49bdbf413e70b5b10010 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352396418302007 kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 32 2018 9-20
spelling	10.1016/j.ebiom.2018.05.035 doi (DE-627)DOAJ040202143 (DE-599)DOAJaffa62f8204a49bdbf413e70b5b10010 DE-627 ger DE-627 rakwb eng R5-920 Jonathan B. Lin verfasserin aut Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. Here, we show that despite their frequent self-renewal, macrophages from old mice exhibited numerous signs of aging, such as impaired oxidative respiration. Transcriptomic profiling of aged murine macrophages revealed dysregulation of diverse cellular pathways, especially in cholesterol homeostasis, that manifested in altered oxysterol signatures. Although the levels of numerous oxysterols in human peripheral blood mononuclear cells and plasma exhibited age-associated changes, plasma 24-hydroxycholesterol levels were specifically associated with AMD. These novel findings demonstrate that oxysterol levels can discriminate disease from physiologic aging. Furthermore, modulation of cholesterol homeostasis may be a novel strategy for treating age-associated diseases in which macrophage aging is pathogenic. Keywords: Age-related macular degeneration, Aging, Lipids, Cholesterol Medicine R Medicine (General) Abdoulaye Sene verfasserin aut Andrea Santeford verfasserin aut Hideji Fujiwara verfasserin aut Rohini Sidhu verfasserin aut Marianne M. Ligon verfasserin aut Vikram A. Shankar verfasserin aut Norimitsu Ban verfasserin aut Indira U. Mysorekar verfasserin aut Daniel S. Ory verfasserin aut Rajendra S. Apte verfasserin aut In EBioMedicine Elsevier, 2015 32(2018), Seite 9-20 (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:32 year:2018 pages:9-20 https://doi.org/10.1016/j.ebiom.2018.05.035 kostenfrei https://doaj.org/article/affa62f8204a49bdbf413e70b5b10010 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352396418302007 kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 32 2018 9-20
allfields_unstemmed	10.1016/j.ebiom.2018.05.035 doi (DE-627)DOAJ040202143 (DE-599)DOAJaffa62f8204a49bdbf413e70b5b10010 DE-627 ger DE-627 rakwb eng R5-920 Jonathan B. Lin verfasserin aut Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. Here, we show that despite their frequent self-renewal, macrophages from old mice exhibited numerous signs of aging, such as impaired oxidative respiration. Transcriptomic profiling of aged murine macrophages revealed dysregulation of diverse cellular pathways, especially in cholesterol homeostasis, that manifested in altered oxysterol signatures. Although the levels of numerous oxysterols in human peripheral blood mononuclear cells and plasma exhibited age-associated changes, plasma 24-hydroxycholesterol levels were specifically associated with AMD. These novel findings demonstrate that oxysterol levels can discriminate disease from physiologic aging. Furthermore, modulation of cholesterol homeostasis may be a novel strategy for treating age-associated diseases in which macrophage aging is pathogenic. Keywords: Age-related macular degeneration, Aging, Lipids, Cholesterol Medicine R Medicine (General) Abdoulaye Sene verfasserin aut Andrea Santeford verfasserin aut Hideji Fujiwara verfasserin aut Rohini Sidhu verfasserin aut Marianne M. Ligon verfasserin aut Vikram A. Shankar verfasserin aut Norimitsu Ban verfasserin aut Indira U. Mysorekar verfasserin aut Daniel S. Ory verfasserin aut Rajendra S. Apte verfasserin aut In EBioMedicine Elsevier, 2015 32(2018), Seite 9-20 (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:32 year:2018 pages:9-20 https://doi.org/10.1016/j.ebiom.2018.05.035 kostenfrei https://doaj.org/article/affa62f8204a49bdbf413e70b5b10010 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352396418302007 kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 32 2018 9-20
allfieldsGer	10.1016/j.ebiom.2018.05.035 doi (DE-627)DOAJ040202143 (DE-599)DOAJaffa62f8204a49bdbf413e70b5b10010 DE-627 ger DE-627 rakwb eng R5-920 Jonathan B. Lin verfasserin aut Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. Here, we show that despite their frequent self-renewal, macrophages from old mice exhibited numerous signs of aging, such as impaired oxidative respiration. Transcriptomic profiling of aged murine macrophages revealed dysregulation of diverse cellular pathways, especially in cholesterol homeostasis, that manifested in altered oxysterol signatures. Although the levels of numerous oxysterols in human peripheral blood mononuclear cells and plasma exhibited age-associated changes, plasma 24-hydroxycholesterol levels were specifically associated with AMD. These novel findings demonstrate that oxysterol levels can discriminate disease from physiologic aging. Furthermore, modulation of cholesterol homeostasis may be a novel strategy for treating age-associated diseases in which macrophage aging is pathogenic. Keywords: Age-related macular degeneration, Aging, Lipids, Cholesterol Medicine R Medicine (General) Abdoulaye Sene verfasserin aut Andrea Santeford verfasserin aut Hideji Fujiwara verfasserin aut Rohini Sidhu verfasserin aut Marianne M. Ligon verfasserin aut Vikram A. Shankar verfasserin aut Norimitsu Ban verfasserin aut Indira U. Mysorekar verfasserin aut Daniel S. Ory verfasserin aut Rajendra S. Apte verfasserin aut In EBioMedicine Elsevier, 2015 32(2018), Seite 9-20 (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:32 year:2018 pages:9-20 https://doi.org/10.1016/j.ebiom.2018.05.035 kostenfrei https://doaj.org/article/affa62f8204a49bdbf413e70b5b10010 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352396418302007 kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 32 2018 9-20
allfieldsSound	10.1016/j.ebiom.2018.05.035 doi (DE-627)DOAJ040202143 (DE-599)DOAJaffa62f8204a49bdbf413e70b5b10010 DE-627 ger DE-627 rakwb eng R5-920 Jonathan B. Lin verfasserin aut Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. Here, we show that despite their frequent self-renewal, macrophages from old mice exhibited numerous signs of aging, such as impaired oxidative respiration. Transcriptomic profiling of aged murine macrophages revealed dysregulation of diverse cellular pathways, especially in cholesterol homeostasis, that manifested in altered oxysterol signatures. Although the levels of numerous oxysterols in human peripheral blood mononuclear cells and plasma exhibited age-associated changes, plasma 24-hydroxycholesterol levels were specifically associated with AMD. These novel findings demonstrate that oxysterol levels can discriminate disease from physiologic aging. Furthermore, modulation of cholesterol homeostasis may be a novel strategy for treating age-associated diseases in which macrophage aging is pathogenic. Keywords: Age-related macular degeneration, Aging, Lipids, Cholesterol Medicine R Medicine (General) Abdoulaye Sene verfasserin aut Andrea Santeford verfasserin aut Hideji Fujiwara verfasserin aut Rohini Sidhu verfasserin aut Marianne M. Ligon verfasserin aut Vikram A. Shankar verfasserin aut Norimitsu Ban verfasserin aut Indira U. Mysorekar verfasserin aut Daniel S. Ory verfasserin aut Rajendra S. Apte verfasserin aut In EBioMedicine Elsevier, 2015 32(2018), Seite 9-20 (DE-627)802540074 (DE-600)2799017-5 23523964 nnns volume:32 year:2018 pages:9-20 https://doi.org/10.1016/j.ebiom.2018.05.035 kostenfrei https://doaj.org/article/affa62f8204a49bdbf413e70b5b10010 kostenfrei http://www.sciencedirect.com/science/article/pii/S2352396418302007 kostenfrei https://doaj.org/toc/2352-3964 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 32 2018 9-20
language	English
source	In EBioMedicine 32(2018), Seite 9-20 volume:32 year:2018 pages:9-20
sourceStr	In EBioMedicine 32(2018), Seite 9-20 volume:32 year:2018 pages:9-20
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Medicine R Medicine (General)
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container_title	EBioMedicine
authorswithroles_txt_mv	Jonathan B. Lin @@aut@@ Abdoulaye Sene @@aut@@ Andrea Santeford @@aut@@ Hideji Fujiwara @@aut@@ Rohini Sidhu @@aut@@ Marianne M. Ligon @@aut@@ Vikram A. Shankar @@aut@@ Norimitsu Ban @@aut@@ Indira U. Mysorekar @@aut@@ Daniel S. Ory @@aut@@ Rajendra S. Apte @@aut@@
publishDateDaySort_date	2018-01-01T00:00:00Z
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language_de	englisch
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callnumber-first	R - Medicine
author	Jonathan B. Lin
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topic_title	R5-920 Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging
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title	Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging
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title_full	Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging
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author_browse	Jonathan B. Lin Abdoulaye Sene Andrea Santeford Hideji Fujiwara Rohini Sidhu Marianne M. Ligon Vikram A. Shankar Norimitsu Ban Indira U. Mysorekar Daniel S. Ory Rajendra S. Apte
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title_sort	oxysterol signatures distinguish age-related macular degeneration from physiologic aging
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title_auth	Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging
abstract	Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. Here, we show that despite their frequent self-renewal, macrophages from old mice exhibited numerous signs of aging, such as impaired oxidative respiration. Transcriptomic profiling of aged murine macrophages revealed dysregulation of diverse cellular pathways, especially in cholesterol homeostasis, that manifested in altered oxysterol signatures. Although the levels of numerous oxysterols in human peripheral blood mononuclear cells and plasma exhibited age-associated changes, plasma 24-hydroxycholesterol levels were specifically associated with AMD. These novel findings demonstrate that oxysterol levels can discriminate disease from physiologic aging. Furthermore, modulation of cholesterol homeostasis may be a novel strategy for treating age-associated diseases in which macrophage aging is pathogenic. Keywords: Age-related macular degeneration, Aging, Lipids, Cholesterol
abstractGer	Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. Here, we show that despite their frequent self-renewal, macrophages from old mice exhibited numerous signs of aging, such as impaired oxidative respiration. Transcriptomic profiling of aged murine macrophages revealed dysregulation of diverse cellular pathways, especially in cholesterol homeostasis, that manifested in altered oxysterol signatures. Although the levels of numerous oxysterols in human peripheral blood mononuclear cells and plasma exhibited age-associated changes, plasma 24-hydroxycholesterol levels were specifically associated with AMD. These novel findings demonstrate that oxysterol levels can discriminate disease from physiologic aging. Furthermore, modulation of cholesterol homeostasis may be a novel strategy for treating age-associated diseases in which macrophage aging is pathogenic. Keywords: Age-related macular degeneration, Aging, Lipids, Cholesterol
abstract_unstemmed	Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. Here, we show that despite their frequent self-renewal, macrophages from old mice exhibited numerous signs of aging, such as impaired oxidative respiration. Transcriptomic profiling of aged murine macrophages revealed dysregulation of diverse cellular pathways, especially in cholesterol homeostasis, that manifested in altered oxysterol signatures. Although the levels of numerous oxysterols in human peripheral blood mononuclear cells and plasma exhibited age-associated changes, plasma 24-hydroxycholesterol levels were specifically associated with AMD. These novel findings demonstrate that oxysterol levels can discriminate disease from physiologic aging. Furthermore, modulation of cholesterol homeostasis may be a novel strategy for treating age-associated diseases in which macrophage aging is pathogenic. Keywords: Age-related macular degeneration, Aging, Lipids, Cholesterol
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title_short	Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging
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Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging

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