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Cited by 152Genomics and Chromatin DynamicsNuclear Structure and FunctionTelomeres, Telomerase, and Senescence

Age‐associated increase in heterochromatic marks in murine and primate tissues

Open access
Kreiling, Jill A., Tamamori‐Adachi, Mimi, Sexton, Alec N., Jeyapalan, Jessie C., Munoz‐Najar, Ursula, Peterson, Abigail L., Manivannan, Jayameenakshi, Rogers, Elizabeth S. +3 more·2011·Aging Cell
DOI 10.1111/j.1474-9726.2010.00666.xPMC PMC3079313
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Abstract

Summary: Chromatin is highly dynamic and subject to extensive remodeling under many physiologic conditions. Changes in chromatin that occur during the aging process are poorly documented and understood in higher organisms, such as mammals. We developed an immunofluorescence assay to quantitatively detect, at the single cell level, changes in the nuclear content of chromatin‐associated proteins. We found increased levels of the heterochromatin‐associated proteins histone macro H2A (mH2A) and heterochromatin protein 1 beta (HP1β) in human fibroblasts during replicative senescence in culture, and for the first time, an age‐associated increase in these heterochromatin marks in several tissues of mice and primates. Mouse lung was characterized by monophasic mH2A expression histograms at both ages, and an increase in mean staining intensity at old age. In the mouse liver, we observed increased age‐associated localization of mH2A to regions of pericentromeric heterochromatin. In the skeletal muscle, we found two populations of cells with either low or high mH2A levels. This pattern of expression was similar in mouse and baboon, and showed a clear increase in the proportion of nuclei with high mH2A levels in older animals. The frequencies of cells displaying evidence of increased heterochromatinization are too high to be readily accounted for by replicative or oncogene‐induced cellular senescence, and are prominently found in terminally differentiated, postmitotic tissues that are not conventionally thought to be susceptible to senescence. Our findings distinguish specific chromatin states in individual cells of mammalian tissues, and provide a foundation to investigate further the progressive epigenetic changes that occur during aging.

Integrity signals

Registry

Crossref · 10.1111/j.1474-9726.2010.00666.x

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 23 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    mH2A and HP1β levels increase in human fibroblasts during replicative senescence in culture.

    “We find increased levels of the heterochromatin-associated proteins histone macro H2A (mH2A) and heterochromatin protein 1 beta (HP1β) in human fibroblasts during replicative senescence in culture”
    Quote in the paperSubstantial claim
  • Findingown data

    In cultured fibroblasts, mH2A and HP1β nuclear content correlate strongly within individual cells across every replicative age.

    “Double staining of cultures with antibodies against both mH2A and HP1β showed a high level of correlation at the single-cell level at all replicative ages.”
    Quote in the paperSubstantial claim
  • Findingown data

    The biphasic pattern of mH2A expression in skeletal muscle is similar in mouse and baboon.

    “This pattern of expression was similar in mouse and baboon”
    • Also stated in: § Discussion · plain
      “The pattern of expression was very similar in mouse and baboon.”
    Quote in the paperSubstantial claim
  • Findingown data

    mH2A and HP1β nuclear staining intensity increases with passage in cultured human fibroblasts.

    “Images acquired under these conditions for mH2A and HP1β (Fig. 1), two known components of SAHF, showed a clear passage-associated increase in nuclear staining intensity.”
    Quote in the paperSubstantial claim
  • Findingown data

    In mouse liver, mH2A localization to pericentromeric heterochromatin regions increases with age.

    “In the mouse liver we observed increased age-associated localization of mH2A to regions of pericentromeric heterochromatin.”
    • Also stated in: § Expression of heterochromatic marks in murine tissues · plain
      “old nuclei typically display prominent mH2A foci that colocalize with the DAPI foci.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Age-related differences in mH2A immunofluorescence intensity reflect differences in target protein amount rather than differences in antibody access, epitope availability, or tissue processing between young and old samples.
    • Rests on an assumption: The young and old animals compared differ in age but not in other factors that would alter mH2A levels.
  • The quote only partly states this claim. 3
  • May combine two claims. 26
  • Classified as probably not a substantial claim. 19

  • The quote only partly states this claim.

    Findingown data

    mH2A protein expression is increased 3-fold in late passage human fibroblasts.

    “We found that mH2A expression was increased 3-fold in late passage cells”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In human fibroblasts approaching senescence, mH2A upregulation correlates with p16 upregulation, while γH2AX or 53BP1 upregulation does not correlate with p16.

    “We have also observed no correlation between the upregulation of γ H2AX or 53BP1 and p16, but we did observe a correlation between the upregulation of mH2A and p16 (data not shown).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    In LF1 human diploid fibroblasts, mH2A increase occurs with essentially the same kinetics as SA-β-Gal and SAHF as cells approach senescence.

    “We observed the same relationship in LF1 HDF using the quantitative mH2A assay (data not shown).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The overall mean mH2A intensity in old baboon skin specimens increased but fell just below statistical significance (p = 0.065).

    “The overall mean intensity in the old specimens increased, but fell just below statistical significance (p = 0.065).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Findingown data

    The authors have recently been able to obtain quantitative information on H3K9Me3 and H3K27Me3.

    “we have recently been able to obtain quantitative information on H3K9Me3 and H3K27Me3.”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingcitation

    The authors confirmed in baboon muscle that DDR-positive cell frequency is very low and does not increase with age.

    “a finding that we confirmed in baboon muscle (Jeyapalan et al., 2007).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Jeyapalan et al., 2007

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Total mH2A intensity in mouse liver increases with age, but normalized mH2A intensity does not increase significantly because old liver nuclei are larger and more polyploid.

    “Examination of liver tissue showed that total mH2A intensity increased with age; however, because of a significant increase in the size and volume of the liver nuclei in old animals (due to the age-associated polyploidization seen in this tissue) the normalized mH2A intensity did not increase significantly.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Age-related differences in mH2A immunofluorescence intensity reflect differences in target protein amount rather than differences in antibody access, epitope availability, or tissue processing between young and old samples.
    • Rests on an assumption: The young and old animals compared differ in age but not in other factors that would alter mH2A levels.

  • May combine two claims.

    Findingown data

    In young mouse liver nuclei, mH2A staining is fairly uniform, while old nuclei show prominent mH2A foci overlapping DAPI foci.

    “while young nuclei stain relatively uniformly with mH2A, old nuclei typically display prominent mH2A foci that colocalize with the DAPI foci.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Age-related differences in mH2A immunofluorescence intensity reflect differences in target protein amount rather than differences in antibody access, epitope availability, or tissue processing between young and old samples.
    • Rests on an assumption: The young and old animals compared differ in age but not in other factors that would alter mH2A levels.

  • May combine two claims.

    Findingown data

    In liver, overall mH2A levels increase with age, but age-related polyploidization obscures this increase, so the ratio of mH2A to DAPI changes little.

    “In the liver, while we saw an overall increase in mH2A levels, this was obscured by the polyploidization that occurs with age in this tissue, so the ratios of mH2A to DAPI did not change much.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Polyploidization occurs with age in liver tissue.

  • May combine two claims.

    Findingcitation

    Fewer than 2% of baboon skeletal muscle cells show telomeric damage, and this proportion stays constant with age.

    “we observed very low levels (<2%) of cells with telomeric damage, and their number did not increase with age in the baboon (Jeyapalan et al., 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Jeyapalan et al., 2007

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    In mouse skeletal muscle, SA-β-Gal-positive cells are rare (<1%) and do not become more frequent with age.

    “mouse skeletal muscle contains very few SA-β-Gal positive cells (<1%) and their frequency does not increase with age (our observations).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In old mice, lung mH2A histograms are broadened, shifted to higher intensities, and often have high-intensity shoulders.

    “In old animals the histograms were broadened, shifted to higher intensities, and often displayed high intensity shoulders.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In young mouse lung and liver, about 30% of nuclei have at least one mH2A-positive pericentromeric focus, and this number doubles in older animals.

    “In both lung and liver, approximately 30% of nuclei had at least one mH2A-postive pericentromeric focus in young animals, while the number of nuclei containing mH2A-positive foci doubled in older animals (Fig. 5C).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Age-related differences in mH2A immunofluorescence intensity reflect differences in target protein amount rather than differences in antibody access, epitope availability, or tissue processing between young and old samples.
    • Rests on an assumption: The young and old animals compared differ in age but not in other factors that would alter mH2A levels.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    SAHF contain HP1, mH2A, and H3K9Me3.

    “SAHF contain heterochromatin protein 1 (HP1), the histone variant macro H2A (mH2A) and repressive histone marks such as histone H3 trimethylated on lysine 9 (H3K9Me3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The increases in mH2A and HP1β in late passage cells are statistically significant across three separate experiments and correlate with microscopic assay results.

    “Both results were statistically significant across three separate experiments and correlate well with the increases observed with the microscopic assay.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Global DNA methylation decreases in aging cells and organisms.

    “Global decreases in DNA methylation have been documented in aging cells and organisms (Wilson et al., 1987; Sedivy et al., 2008; Calvanese et al., 2009).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Wilson et al., 1987

      Not checked in the free run.

    • cites Sedivy et al., 2008

      Not checked in the free run.

    • cites Calvanese et al., 2009

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Replicative senescence due to replicative exhaustion is caused by telomere shortening.

    “The underlying cause of senescence due to replicative exhaustion is telomere shortening (Bodnar et al., 1998; Wright & Shay, 2002).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Bodnar et al., 1998

      Not checked in the free run.

    • cites Wright & Shay, 2002

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    In human fibroblasts, counts of cells, DNA amounts, and H2B or H3 levels remain tightly correlated and unchanged at every replicative age.

    “We found that cell number, DNA content, and H2B or H3 expression were very closely correlated and constant across all replicative ages.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The results support placing γH2AX, 53BP1, and p21 together in one pathway, and HIRA, mH2A, and p16 together in a separate pathway.

    “These data are consistent with γ H2AX, 53BP1 and p21 being in one pathway, and with HIRA, mH2A and p16 being in a distinct pathway.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    For abundant chromatin proteins, the dilutions usually advised do not fall within the linear response range; one must titrate to saturating concentrations for accurate quantification.

    “for abundant proteins, such as chromatin components, recommended antibody dilutions are not in the linear response range. It is first necessary to titrate the antibody concentration such that using either more antibody or longer incubation times does not result in increased signal.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    Whether SAHF form in an organismal context is not known.

    “but whether SAHF form in an organismal context is not known.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A terminal step of senescence induced by telomere exhaustion, oncogenes, and genotoxic stress is extensive heterochromatinization and formation of SAHF.

    “A terminal step of senescence frequently induced by telomere exhaustion, oncogenes and genotoxic stress is extensive heterochromatinization and formation of nuclear structures designated senescence-associated heterochromatin foci (SAHF) (Narita et al., 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Narita et al., 2003

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Because mouse lung mH2A histograms lack separate peaks, the authors infer that every lung cell type shows the age-related mH2A rise.

    “The absence of distinct subpopulations in our immunofluorescence data (which would appear as shoulders or multiple peaks in the histograms) indicate that all cell types are affected by increased mH2A levels, although it remains possible that some cell types may be affected more than others.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Similar findings to the liver mH2A localization increase have been reported in mouse liver using an H3K9Me3 antibody.

    “(very similar findings have recently been reported in mouse liver using an antibody to H3K9Me3 (Jin et al., 2010)).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Jin et al., 2010

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    Another advantage is that only a small amount of biological material is needed, at the limit a handful of 6-8 μm tissue sections, allowing examination of microscopic structures such as stem cells in their niches or limited archival material.

    “Another important advantage is the small amount of biological material that is needed (at the limit, a handful of 6–8 μm tissue sections) allowing the examination of microscopic structures, such as stem cells in their native niches, or limited and valuable archival material.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    In immunoblots, both antibodies visualize a single major band for mH2A1.1 or mH2A1.2, depending on the tissue.

    “In immunoblots, both antibodies visualize a single major band for mH2A1.1 or mH2A1.2, depending on the tissue.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    The age-associated increase in heterochromatin marks found here and in other studies contrasts with the well-documented age-associated decrease in DNA methylation.

    “The age-associated increase of heterochromatin marks documented here and in other recent studies (Sarg et al., 2002; Jin et al., 2010; Wood et al., 2010) contrasts with the well documented decrease in DNA methylation (Sedivy et al., 2008; Calvanese et al., 2009).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Sarg et al., 2002

      Not checked in the free run.

    • cites Jin et al., 2010

      Not checked in the free run.

    • cites Wood et al., 2010

      Not checked in the free run.

    • Rests on an assumption: mH2A and HP1β are constituents of heterochromatin.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The independently raised mH2A1.1 and mH2A1.2 antibodies behaved equivalently in all assays presented.

    “The independently raised mH2A1.1. and mH2A1.2 antibodies behaved equivalently in all the assays presented in this communication.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The principles of the assay can be generalized to any nuclear antigen of interest.

    “but the principles of the assay are generalizable to any nuclear antigen of interest.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The resulting antisera react with both mH2A1.1 and mH2A1.2 proteins.

    “Not surprisingly, the resulting antisera react with both the mH2A1.1 and mH2A1.2 proteins.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    These results together are consistent with the authors' findings and indicate an increase in transcriptionally repressive heterochromatin, especially at gene coding regions.

    “Together, these results are consistent with our findings and indicative an increase in transcriptionally repressive heterochromatin, particularly at gene coding regions.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: mH2A and HP1β are constituents of heterochromatin.

  • May combine two claims.

    Premisecitation

    In mouse muscle, DDR-positive cells occur at very low frequencies and their frequency does not increase with age.

    “Similarly, mouse muscle shows very low frequencies of DDR-positive cells which do not increase with age (Wang et al., 2009)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wang et al., 2009

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Like any immunofluorescence-based assay, it can be limited by the availability of antibodies with adequate affinity and limited cross-reactivity.

    “As is the case for any immunofluorescence-based assay, it can be limited by the availability of antibodies of adequate affinity and limited cross-reactivity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    H3K9Me3 and HP1 levels increase with age, suggesting strong conservation of these processes.

    “Of relevance to our findings, the levels of H3K9Me3 and HP1 increased with age, hinting at strong conservation in these processes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wood et al., 2010

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The most likely explanation for the weaker skin mH2A age trend is environmental exposure obscuring an underlying age-associated pattern.

    “The most likely explanation is that the skin is subject to environmental exposure, which could obscure an underlying age-associated pattern.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The assay was extensively developed and validated by immunoblotting and can accurately assess differences of 1.5-fold, or lower with sufficiently large numbers of cells scored.

    “The assay has undergone extensive development and validation by immunoblotting, and is capable of accurately assessing differences of 1.5-fold (and even lower if sufficiently large numbers of cells are scored).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    In addition to overall increases in mH2A in some tissues, mH2A undergoes profound age-associated redistribution.

    “Thus, in addition to an overall increase in mH2A levels in certain tissues, mH2A can also undergo a profound age-associated redistribution.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    p16 is an important marker of cellular senescence.

    “another important marker of senescence (Krishnamurthy et al., 2004)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Krishnamurthy et al., 2004

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Control immunofluorescence experiments using mH2A1 knockout mouse MEF and tissues assessed nonspecific background.

    “Control immunofluorescence experiments using mH2A1 knockout mouse MEF and tissues to assess nonspecific background are shown in Fig. S5.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The authors focused on mH2A and HP1β, known heterochromatin constituents, because they could obtain very good antibodies against them.

    “Here we have focused on mH2A and HP1β, two known constituents of heterochromatin against which we were able to locate very good antibodies”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: mH2A and HP1β are constituents of heterochromatin.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    All microscope settings and exposure times were set below saturation and kept constant for all images in one experiment.

    “All microscope settings and exposure times were set to collect images below saturation and were kept constant for all images taken in one experiment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The additional mH2A in old cells is targeted, at least partly, to constitutive heterochromatin, though this does not explain the overall increase, and higher signal is seen throughout the nucleus.

    “It thus appears that the additional mH2A in old cells is targeted, at least in part, to constitutive heterochromatin, although this does not account for the overall increase, and higher signal is evident throughout the nucleus.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: mH2A and HP1β are constituents of heterochromatin.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Little is known about the epigenetics of aging, but chromatin is subject to profound age-associated changes.

    “We still know very little about the epigenetics of aging, but it is rapidly coming to light that chromatin is subject to profound age-associated changes (Fraga et al., 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Fraga et al., 2005

      Not checked in the free run.

43 of 43

  • The paper relies on this without support.

    The anti-centromere autoantibody used to verify pericentromeric localization recognizes mouse centromeres specifically.

    “The pericentromeric localization of the mH2A foci was verified using a human anti-centromere autoantibody.”

  • The paper relies on this without support.

    Age-related differences in mH2A immunofluorescence intensity reflect differences in target protein amount rather than differences in antibody access, epitope availability, or tissue processing between young and old samples.

    “Elevated levels of mH2A were readily apparent in lung nuclei of 24 month old C57BL/6 females (Fig. 4A).”

  • The paper relies on this without support.

    The young and old animals compared differ in age but not in other factors that would alter mH2A levels.

    “the mean levels of mH2A calculated for groups of five young (5 month) and old (36 month) male animals showed a highly significant 1.9-fold increase in the old group (Fig. 4D).”

  • The paper relies on this without support.

    mH2A and HP1β are constituents of heterochromatin.

    “two known constituents of heterochromatin”

  • The paper relies on this without support.

    Polyploidization occurs with age in liver tissue.

    “the polyploidization that occurs with age in this tissue”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The same changes documented in ageing cells, such as demethylation of retrotransposons and satellite DNA and high levels of their transcription, are also observed in human cancer.

    “Of note, the same changes documented in ageing cells, such as demethylation of retrotransposons and satellite DNA and high levels of their transcription, are also observed in human cancer 73-75 .”

    From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [74]

  • Demethylation of retrotransposons and satellites and high levels of their transcription are observed in ageing cells and in human cancer.

    “Demethylation of retrotransposons and satellites and high levels of their transcription are observed in ageing cells 47 and in human cancer 73-75 .”

    From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [74]

  • SAHF contain silent heterochromatin domains consisting of H3K9Me2/3, macroH2A, and HP1 proteins.

    “Structurally, SAHF contain silent hetero-chromatin domains consisting of a di-or tri-methylated lysine 9 of histone H3 (H3K9Me2/3), a histone H2A variant (macroH2A), and heterochromatin protein 1 (HP1) proteins [74, 76, 77].”

    From Markers of cellular senescence. Telomere shortening as a marker of cellular senescence (2016) · cites this paper as [77]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Old lung histograms both have and lack shoulders

    Major

    The results say old mouse lung histograms often have high-intensity shoulders. The discussion instead treats shoulders as absent when inferring that there are no distinct cell subpopulations.

  • Mouse muscle DNA-damage frequency is described as unchanged despite rising fivefold

    Minor

    The paper reports DDR-positive cells in mouse skeletal muscle increasing from 0.3% in young animals to 1.5% in old animals, but later says their frequency does not increase with age.

2 of 2

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Authors
Kreiling, J. A., Tamamori‐Adachi, M., Sexton, A. N., Jeyapalan, J. C., Munoz‐Najar, U., Peterson, A. L., Manivannan, J., Rogers, E. S., Pchelintsev, N. A., Adams, P. D., & Sedivy, J. M.
Affiliations
  • Brown University (US)
  • Cancer Research UK Scotland Institute (GB)
Corresponding author
  • Kreiling, Jill A.
  • Sedivy, John M.
ORCID
Venue
Aging Cell
Publisher
Wiley
Published
2010-12-30
Volume
10
Issue
2
Pages
292-304
ISSN
  • 1474-9718 (ISSN-L)
  • 1474-9726
DOI
10.1111/j.1474-9726.2010.00666.x
PMC
PMC3079313
OpenAlex
W1918957812
Cited by
152
References
62
Citations by year
2026: 2 · 2025: 3 · 2024: 10 · 2023: 7 · 2022: 6 · 2021: 12 · 2020: 6 · 2019: 14 · 2018: 14 · 2017: 13 · 2016: 10 · 2015: 13 · 2014: 8 · 2013: 16 · 2012: 13
FWCI
4.43
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Aging Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion)
Funders
  • Brown University
  • University of Pennsylvania
  • National Institutes of Health
  • Biotechnology and Biological Sciences Research Council (BB/H021019/1)
  • National Institute on Aging (P01AG031862, R37AG016694)
  • National Center for Research Resources (P20RR015578)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Keywords
aging, heterochromatin, HP1β, chromatin remodeling, replicative senescence, pericentromeric heterochromatin, skeletal muscle, lung, liver, postmitotic tissues, epigenetic modifications, baboons
MeSH terms
Chromobox Protein Homolog 5, Aging, Animals, Fibroblasts, Fluorescent Antibody Technique, Heterochromatin, Humans, Liver, Lung, Primates, Muscle, Skeletal, Epigenesis, Genetic, Mice

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