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. 2021 May 30;12(9):695–716. doi: 10.1007/s13238-021-00852-9

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

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Aging-related loss of genomic and epigenomic stability in the monkey hippocampus. (A) Immunohistochemical staining of γH2A.X in the indicated regions of the hippocampus from young and old monkeys. Representative images are shown on the left; γH2A.X-positive cells are quantified as fold changes of their numbers in the old DG, CA1 and CA3 regions vs. in young counterparts, shown as means ± SEM on the right. Black arrows indicate the γH2A.X-positive cells. Scale bars, 20 μm and 10 μm (zoomed-in image). Young, n = 8; old, n = 8 monkeys. ***P < 0.001; **P < 0.01. (B) Immunofluorescence staining of dsDNA in the indicated regions of the hippocampus from young and old monkeys. Representative images are shown on the left; cytoplasmic dsDNA-positive cells are quantified as fold changes of their numbers in the old DG, CA1 and CA3 regions vs. in young counterparts, shown as means ± SEM on the right. Red arrows indicate the cytoplasm-localized dsDNA. Scale bars, 20 μm and 10 μm (zoomed-in image). Young, n = 8; old, n = 8 monkeys. ****P < 0.0001; ***P < 0.001. (C) Immunofluorescence staining of H3K9me3 in the indicated regions of the hippocampus from young and old monkeys. Representative images are shown on the left; H3K9me3-positive cells are quantified as fold changes of their numbers in the old DG, CA1 and CA3 regions vs. in young counterparts, shown as means ± SEM on the right. Red arrows indicate the H3K9me3-negative cells. Scale bars, 20 μm and 10 μm (zoomed-in image). Young, n = 8; old, n = 8 monkeys. **P < 0.01. (D) Immunofluorescence staining of HP1γ in the indicated regions of the hippocampus from young and old monkeys. Representative images are shown on the left, arrows indicate HP1γ -negative cells; while HP1γ-positive cells in the old DG, CA1 and CA3 regions vs. young regions are quantified as fold changes (means ± SEM) on the right. Black arrows indicate the HP1γ-negative cells. Scale bars, 20 μm and 10 μm (zoomed-in image). Young, n = 8; old, n = 8 monkeys. **P < 0.01. (E) Immunofluorescence staining of LINE-1 ORF2p in the indicated regions of the hippocampus from young and old monkeys. Representative images are shown on the left; LINE-1 ORF2p-positive cells are quantified as fold changes of their numbers in the old DG, CA1 and CA3 regions vs. in young counterparts, shown as means ± SEM on the right. Red arrows indicate the LINE-1 ORF2p-positive cells. Scale bars, 50 μm and 10 μm (Zoomed in image). Young, n = 8; old, n = 8 monkeys. ****P < 0.0001