Astrocyte expression of aging-associated markers positively correlates with neurodegeneration in the frontal lobe of the rhesus macaque brain
IntroductionAs the population over the age of 65 increases, rates of neurodegenerative disorders and dementias will rise – necessitating further research into the cellular and molecular mechanisms that contribute to brain aging. With the critical importance of astrocytes to neuronal health and funct...
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| Format: | Article |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2024.1368517/full |
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| author | Miranda D. Horn Sophia C. Forest Ahmad A. Saied Andrew G. MacLean Andrew G. MacLean Andrew G. MacLean Andrew G. MacLean |
| author_facet | Miranda D. Horn Sophia C. Forest Ahmad A. Saied Andrew G. MacLean Andrew G. MacLean Andrew G. MacLean Andrew G. MacLean |
| author_sort | Miranda D. Horn |
| collection | DOAJ |
| description | IntroductionAs the population over the age of 65 increases, rates of neurodegenerative disorders and dementias will rise – necessitating further research into the cellular and molecular mechanisms that contribute to brain aging. With the critical importance of astrocytes to neuronal health and functioning, we hypothesized that alterations in astrocyte expression of aging-associated markers p16INK4a (p16) and sirtuin 1 (SIRT1) with age would correlate with increased rates of neurodegeneration, as measured by FluoroJade C (FJC) staining.MethodsTo test this hypothesis, 19 rhesus macaques at the Tulane National Primate Research Center were selected based on the following criteria: archival FFPE CNS tissue available to use, no noted neuropathology, and an age range of 5–30 years. Tissues were cut at 5 μm and stained for GFAP, p16, SIRT1, and FJC, followed by whole-slide imaging and HALO® image analysis for percentage of marker-positive cells and relative intensity of each stain.ResultsWe found the percentage of p16+ cells increases with age in total cells and astrocytes of the frontal (p = 0.0021, p = 0.0012 respectively) and temporal (p = 0.0226, p = 0.0203 respectively) lobes, as well as the relative intensity of p16 staining (frontal lobe: p = 0.0060; temporal lobe: p = 0.0269). For SIRT1, we found no correlation with age except for an increase in the relative intensity of SIRT1 in the temporal lobe (p = 0.0033). There was an increase in neurodegeneration, as measured by the percentage of FJC+ cells in the frontal lobe with age (p = 0.0057), as well as in the relative intensity of FJC staining in the frontal (p = 0.0030) and parietal (p = 0.0481) lobes. Importantly, increased p16 and SIRT1 expression in astrocytes correlated with increasing neurodegeneration in the frontal lobe (p = 0.0009, p = 0.0095 respectively).DiscussionTogether, these data suggest that age-associated alterations in astrocytes contribute to neurodegeneration and provide a target for mechanistic studies in the future. |
| first_indexed | 2024-04-24T22:23:55Z |
| format | Article |
| id | doaj.art-a63901b354be480ebbeb0947e4ed7d92 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-24T22:23:55Z |
| publishDate | 2024-03-01 |
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| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-a63901b354be480ebbeb0947e4ed7d922024-03-20T04:32:43ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652024-03-011610.3389/fnagi.2024.13685171368517Astrocyte expression of aging-associated markers positively correlates with neurodegeneration in the frontal lobe of the rhesus macaque brainMiranda D. Horn0Sophia C. Forest1Ahmad A. Saied2Andrew G. MacLean3Andrew G. MacLean4Andrew G. MacLean5Andrew G. MacLean6Brain Institute, Tulane University, New Orleans, LA, United StatesUniversity of Texas, Austin, TX, United StatesTulane National Primate Research Center, Covington, LA, United StatesBrain Institute, Tulane University, New Orleans, LA, United StatesTulane National Primate Research Center, Covington, LA, United StatesTulane Center for Aging, New Orleans, LA, United StatesDepartment of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, United StatesIntroductionAs the population over the age of 65 increases, rates of neurodegenerative disorders and dementias will rise – necessitating further research into the cellular and molecular mechanisms that contribute to brain aging. With the critical importance of astrocytes to neuronal health and functioning, we hypothesized that alterations in astrocyte expression of aging-associated markers p16INK4a (p16) and sirtuin 1 (SIRT1) with age would correlate with increased rates of neurodegeneration, as measured by FluoroJade C (FJC) staining.MethodsTo test this hypothesis, 19 rhesus macaques at the Tulane National Primate Research Center were selected based on the following criteria: archival FFPE CNS tissue available to use, no noted neuropathology, and an age range of 5–30 years. Tissues were cut at 5 μm and stained for GFAP, p16, SIRT1, and FJC, followed by whole-slide imaging and HALO® image analysis for percentage of marker-positive cells and relative intensity of each stain.ResultsWe found the percentage of p16+ cells increases with age in total cells and astrocytes of the frontal (p = 0.0021, p = 0.0012 respectively) and temporal (p = 0.0226, p = 0.0203 respectively) lobes, as well as the relative intensity of p16 staining (frontal lobe: p = 0.0060; temporal lobe: p = 0.0269). For SIRT1, we found no correlation with age except for an increase in the relative intensity of SIRT1 in the temporal lobe (p = 0.0033). There was an increase in neurodegeneration, as measured by the percentage of FJC+ cells in the frontal lobe with age (p = 0.0057), as well as in the relative intensity of FJC staining in the frontal (p = 0.0030) and parietal (p = 0.0481) lobes. Importantly, increased p16 and SIRT1 expression in astrocytes correlated with increasing neurodegeneration in the frontal lobe (p = 0.0009, p = 0.0095 respectively).DiscussionTogether, these data suggest that age-associated alterations in astrocytes contribute to neurodegeneration and provide a target for mechanistic studies in the future.https://www.frontiersin.org/articles/10.3389/fnagi.2024.1368517/fullneurodegenerationnon-human primatehealthspaneugeric agingcellular senescenceinflammaging |
| spellingShingle | Miranda D. Horn Sophia C. Forest Ahmad A. Saied Andrew G. MacLean Andrew G. MacLean Andrew G. MacLean Andrew G. MacLean Astrocyte expression of aging-associated markers positively correlates with neurodegeneration in the frontal lobe of the rhesus macaque brain Frontiers in Aging Neuroscience neurodegeneration non-human primate healthspan eugeric aging cellular senescence inflammaging |
| title | Astrocyte expression of aging-associated markers positively correlates with neurodegeneration in the frontal lobe of the rhesus macaque brain |
| title_full | Astrocyte expression of aging-associated markers positively correlates with neurodegeneration in the frontal lobe of the rhesus macaque brain |
| title_fullStr | Astrocyte expression of aging-associated markers positively correlates with neurodegeneration in the frontal lobe of the rhesus macaque brain |
| title_full_unstemmed | Astrocyte expression of aging-associated markers positively correlates with neurodegeneration in the frontal lobe of the rhesus macaque brain |
| title_short | Astrocyte expression of aging-associated markers positively correlates with neurodegeneration in the frontal lobe of the rhesus macaque brain |
| title_sort | astrocyte expression of aging associated markers positively correlates with neurodegeneration in the frontal lobe of the rhesus macaque brain |
| topic | neurodegeneration non-human primate healthspan eugeric aging cellular senescence inflammaging |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2024.1368517/full |
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