Age-related focal loss of contractile vascular smooth muscle cells in retinal arterioles is accelerated by caveolin-1 deficiency

Cerebral microcirculation is critical for the preservation of brain health, and vascular impairment is associated with age-related neurodegenerative diseases. Because the retina is a component of the central nervous system, cellular changes that occur in the aging retina are likely relevant to the a...

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Published in	Neurobiology of aging Vol. 71; pp. 1 - 12
Main Authors	Reagan, Alaina M., Gu, Xiaowu, Paudel, Sijalu, Ashpole, Nicole M., Zalles, Michelle, Sonntag, William E., Ungvari, Zoltan, Csiszar, Anna, Otalora, Laura, Freeman, Willard M., Stout, Michael B., Elliott, Michael H.
Format	Journal Article
Language	English
Published	United States Elsevier Inc 01.11.2018
Subjects	Aging Alpha smooth muscle actin Animals Apoptosis Arterioles - physiology Caveolin 1 - genetics Caveolin 1 - physiology Caveolin-1 Insulin-Like Growth Factor I - genetics Insulin-Like Growth Factor I - physiology Insulin-like growth factor-1 Male Mice, Inbred C57BL Mice, Knockout Muscle Contraction Muscle, Smooth, Vascular - physiology Retina Retinal Artery - physiology Vasculature Caveolin-1 Aging Insulin-like growth factor-1 Alpha smooth muscle actin Retina Vasculature
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ISSN	0197-4580 1558-1497 1558-1497
DOI	10.1016/j.neurobiolaging.2018.06.039

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Abstract	Cerebral microcirculation is critical for the preservation of brain health, and vascular impairment is associated with age-related neurodegenerative diseases. Because the retina is a component of the central nervous system, cellular changes that occur in the aging retina are likely relevant to the aging brain, and the retina provides the advantage that the entire vascular bed is visible, en face. In this study, we tested the hypothesis that normal, healthy aging alters the contractile vascular smooth muscle cell (VSMC) coverage of retinal arterioles. We found that aging results in a significant reduction of contractile VSMCs in focal patches along arterioles. Focal loss of contractile VSMCs occurs at a younger age in mice deficient in the senescence-associated protein, caveolin-1. Age-related contractile VSMC loss is not exacerbated by genetic depletion of insulin-like growth factor-1. The patchy loss of contractile VSMCs provides a cellular explanation for previous clinical studies showing focal microirregularities in retinal arteriolar responsiveness in healthy aged human subjects and is likely to contribute to age-related retinal vascular complications.
AbstractList	Cerebral microcirculation is critical for the preservation of brain health, and vascular impairment is associated with age-related neurodegenerative diseases. Because the retina is a component of the central nervous system, cellular changes that occur in the aging retina are likely relevant to the aging brain, and the retina provides the advantage that the entire vascular bed is visible, en face. In this study, we tested the hypothesis that normal, healthy aging alters the contractile vascular smooth muscle cell (VSMC) coverage of retinal arterioles. We found that aging results in a significant reduction of contractile VSMCs in focal patches along arterioles. Focal loss of contractile VSMCs occurs at a younger age in mice deficient in the senescence-associated protein, caveolin-1. Age-related contractile VSMC loss is not exacerbated by genetic depletion of insulin-like growth factor-1. The patchy loss of contractile VSMCs provides a cellular explanation for previous clinical studies showing focal microirregularities in retinal arteriolar responsiveness in healthy aged human subjects and is likely to contribute to age-related retinal vascular complications. Cerebral microcirculation is critical for the preservation of brain health and vascular impairment is associated with age-related neurodegenerative diseases. Because the retina is a component of the central nervous system, cellular changes that occur in the aging retina are likely relevant to the aging brain and the retina provides the advantage that the entire vascular bed is visible, en face . In this study, we tested the hypothesis that normal, healthy aging alters the contractile vascular smooth muscle cell (VSMC) coverage of retinal arterioles. We found that aging results in a significant reduction of contractile VSMCs in focal patches along arterioles. Focal loss of contractile VSMCs occurs at a younger age in mice deficient in the senescence-associated protein, caveolin-1 (Cav-1). Age-related contractile VSMC loss is not exacerbated by genetic depletion of insulin-like growth factor-1 (IGF-1). The patchy loss of contractile VSMCs provides a cellular explanation for previous clinical studies showing focal microirregularities in retinal arteriolar responsiveness in healthy aged human subjects and is likely to contribute to age-related retinal vascular complications. Cerebral microcirculation is critical for the preservation of brain health, and vascular impairment is associated with age-related neurodegenerative diseases. Because the retina is a component of the central nervous system, cellular changes that occur in the aging retina are likely relevant to the aging brain, and the retina provides the advantage that the entire vascular bed is visible, en face. In this study, we tested the hypothesis that normal, healthy aging alters the contractile vascular smooth muscle cell (VSMC) coverage of retinal arterioles. We found that aging results in a significant reduction of contractile VSMCs in focal patches along arterioles. Focal loss of contractile VSMCs occurs at a younger age in mice deficient in the senescence-associated protein, caveolin-1. Age-related contractile VSMC loss is not exacerbated by genetic depletion of insulin-like growth factor-1. The patchy loss of contractile VSMCs provides a cellular explanation for previous clinical studies showing focal microirregularities in retinal arteriolar responsiveness in healthy aged human subjects and is likely to contribute to age-related retinal vascular complications.Cerebral microcirculation is critical for the preservation of brain health, and vascular impairment is associated with age-related neurodegenerative diseases. Because the retina is a component of the central nervous system, cellular changes that occur in the aging retina are likely relevant to the aging brain, and the retina provides the advantage that the entire vascular bed is visible, en face. In this study, we tested the hypothesis that normal, healthy aging alters the contractile vascular smooth muscle cell (VSMC) coverage of retinal arterioles. We found that aging results in a significant reduction of contractile VSMCs in focal patches along arterioles. Focal loss of contractile VSMCs occurs at a younger age in mice deficient in the senescence-associated protein, caveolin-1. Age-related contractile VSMC loss is not exacerbated by genetic depletion of insulin-like growth factor-1. The patchy loss of contractile VSMCs provides a cellular explanation for previous clinical studies showing focal microirregularities in retinal arteriolar responsiveness in healthy aged human subjects and is likely to contribute to age-related retinal vascular complications.
Author	Ungvari, Zoltan Freeman, Willard M. Stout, Michael B. Otalora, Laura Paudel, Sijalu Ashpole, Nicole M. Sonntag, William E. Csiszar, Anna Reagan, Alaina M. Zalles, Michelle Gu, Xiaowu Elliott, Michael H.
AuthorAffiliation	a Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA c Department of Cell Biology, Cameron University, Lawton, OK, USA d Department of BioMolecular Sciences, University of Mississippi, Oxford, MS, USA h Department of Nutritional Sciences, University of Oklahoma Health Sciences Center, Oklahoma city, OK, USA f Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA g Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA b Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA e Reynolds Oklahoma Center on Aging & Nathan Shock Center of Excellence in the Biology of Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
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Keywords	Caveolin-1 Aging Insulin-like growth factor-1 Alpha smooth muscle actin Retina Vasculature
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Snippet	Cerebral microcirculation is critical for the preservation of brain health, and vascular impairment is associated with age-related neurodegenerative diseases.... Cerebral microcirculation is critical for the preservation of brain health and vascular impairment is associated with age-related neurodegenerative diseases....
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SubjectTerms	Aging Alpha smooth muscle actin Animals Apoptosis Arterioles - physiology Caveolin 1 - genetics Caveolin 1 - physiology Caveolin-1 Insulin-Like Growth Factor I - genetics Insulin-Like Growth Factor I - physiology Insulin-like growth factor-1 Male Mice, Inbred C57BL Mice, Knockout Muscle Contraction Muscle, Smooth, Vascular - physiology Retina Retinal Artery - physiology Vasculature
Title	Age-related focal loss of contractile vascular smooth muscle cells in retinal arterioles is accelerated by caveolin-1 deficiency
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