The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index; none of the 23 sources its claims cite is checked for support yet.
Age‐associated increase in heterochromatic marks in murine and primate tissues
Open accessAbstract
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.
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48 Own result · 17 Not checked yet · 16 Own method · 16 Own interpretation · 2 No basis given
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“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”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Abstract
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“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.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in cultured fibroblasts
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In the paper
“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.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Abstract
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- Also stated in: § Discussion · plain
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“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.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in cultured fibroblasts
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In the paper
“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.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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.
- Also stated in: § Expression of heterochromatic marks in murine tissues · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“for the first time, an age-associated increase in these heterochromatin marks in several tissues of mice and primates.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Abstract
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“our late passage cells contained 3–5-fold more total protein than early passage cells.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in cultured fibroblasts
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“and are prominently found in terminally differentiated, post mitotic tissues that are not conventionally thought to be susceptible to senescence.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Abstract
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“In skeletal muscle we found two populations of cells with either low or high mH2A levels.”
- Also stated in: § Expression of heterochromatic marks in murine tissues · plain
“Both age groups showed two distinct populations of nuclei with either low or high levels of mH2A”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Abstract
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- Also stated in: § Expression of heterochromatic marks in murine tissues · plain
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“and HP1β was increased 2-fold.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in cultured fibroblasts
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- Probably not a substantial claim. 19
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In the paper
“We found that mH2A expression was increased 3-fold in late passage cells”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in cultured fibroblasts
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in cultured fibroblasts
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In the paper
“We observed the same relationship in LF1 HDF using the quantitative mH2A assay (data not shown).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in cultured fibroblasts
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The overall mean intensity in the old specimens increased, but fell just below statistical significance (p = 0.065).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in primate tissues
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“we have recently been able to obtain quantitative information on H3K9Me3 and H3K27Me3.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
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In the paper
“a finding that we confirmed in baboon muscle (Jeyapalan et al., 2007).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
What the sources say
- Not checked yetcites Jeyapalan et al., 2007
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in murine tissues
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- 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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“while young nuclei stain relatively uniformly with mH2A, old nuclei typically display prominent mH2A foci that colocalize with the DAPI foci.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in murine tissues
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- 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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: Polyploidization occurs with age in liver tissue.
In the paper
“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).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
What the sources say
- Not checked yetcites Jeyapalan et al., 2007
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“mouse skeletal muscle contains very few SA-β-Gal positive cells (<1%) and their frequency does not increase with age (our observations).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In old animals the histograms were broadened, shifted to higher intensities, and often displayed high intensity shoulders.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in murine tissues
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in murine tissues
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Introduction
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“Both results were statistically significant across three separate experiments and correlate well with the increases observed with the microscopic assay.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in cultured fibroblasts
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In the paper
“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).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Introduction
What the sources say
- Not checked yetcites Wilson et al., 1987
- Not checked yetcites Sedivy et al., 2008
- Not checked yetcites Calvanese et al., 2009
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“The underlying cause of senescence due to replicative exhaustion is telomere shortening (Bodnar et al., 1998; Wright & Shay, 2002).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Introduction
What the sources say
- Not checked yetcites Bodnar et al., 1998
- Not checked yetcites Wright & Shay, 2002
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that cell number, DNA content, and H2B or H3 expression were very closely correlated and constant across all replicative ages.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in cultured fibroblasts
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in cultured fibroblasts
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In the paper
“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.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in cultured fibroblasts
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In the paper
“but whether SAHF form in an organismal context is not known.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Introduction
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Probably not a substantial claim.
In the paper
“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).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Introduction
What the sources say
- Not checked yetcites Narita et al., 2003
hedgeddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“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.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
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In the paper
“(very similar findings have recently been reported in mouse liver using an antibody to H3K9Me3 (Jin et al., 2010)).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
What the sources say
- Not checked yetcites Jin et al., 2010
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In immunoblots, both antibodies visualize a single major band for mH2A1.1 or mH2A1.2, depending on the tissue.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Experimental procedures > Antibodies
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
What the sources say
- Not checked yetcites Sarg et al., 2002
- Not checked yetcites Jin et al., 2010
- Not checked yetcites Wood et al., 2010
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: mH2A and HP1β are constituents of heterochromatin.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The independently raised mH2A1.1. and mH2A1.2 antibodies behaved equivalently in all the assays presented in this communication.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Experimental procedures > Antibodies
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“but the principles of the assay are generalizable to any nuclear antigen of interest.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Not surprisingly, the resulting antisera react with both the mH2A1.1 and mH2A1.2 proteins.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Experimental procedures > Antibodies
plain- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results are consistent with our findings and indicative an increase in transcriptionally repressive heterochromatin, particularly at gene coding regions.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: mH2A and HP1β are constituents of heterochromatin.
In the paper
“Similarly, mouse muscle shows very low frequencies of DDR-positive cells which do not increase with age (Wang et al., 2009)”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
What the sources say
- Not checked yetcites Wang et al., 2009
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Of relevance to our findings, the levels of H3K9Me3 and HP1 increased with age, hinting at strong conservation in these processes.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
What the sources say
- Not checked yetcites Wood et al., 2010
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The most likely explanation is that the skin is subject to environmental exposure, which could obscure an underlying age-associated pattern.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in primate tissues
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, in addition to an overall increase in mH2A levels in certain tissues, mH2A can also undergo a profound age-associated redistribution.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in murine tissues
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“another important marker of senescence (Krishnamurthy et al., 2004)”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
What the sources say
- Not checked yetcites Krishnamurthy et al., 2004
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Control immunofluorescence experiments using mH2A1 knockout mouse MEF and tissues to assess nonspecific background are shown in Fig. S5.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Experimental procedures > Antibodies
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we have focused on mH2A and HP1β, two known constituents of heterochromatin against which we were able to locate very good antibodies”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: mH2A and HP1β are constituents of heterochromatin.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All microscope settings and exposure times were set to collect images below saturation and were kept constant for all images taken in one experiment.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Experimental procedures > Quantitative immunofluorescence
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: mH2A and HP1β are constituents of heterochromatin.
In the paper
“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).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
What the sources say
- Not checked yetcites Fraga et al., 2005
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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”
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?
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in murine tissues
“In old animals the histograms were broadened, shifted to higher intensities, and often displayed high intensity shoulders.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
“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.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
“Wang et al. (2009) reported frequencies of DNA damage foci in lung, liver and skeletal muscle of 6.7%, 8.4% and 0.3% in young mice, and 19%, 17% and 1.5% in old animals.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
“Similarly, mouse muscle shows very low frequencies of DDR-positive cells which do not increase with age (Wang et al., 2009), a finding that we confirmed in baboon muscle (Jeyapalan et al., 2007).”
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Metadata
- 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.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2010-12-30
- Volume
- 10
- Issue
- 2
- Pages
- 292-304
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- 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
- green
- www.ncbi.nlm.nih.gov
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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