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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
plain- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Discussion · plain
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In the paper
“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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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“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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In the paper
“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 the paper
“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
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Also stated in: § Expression of heterochromatic marks in murine tissues · plain
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In the paper
“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
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“showed a clear increase in the proportion of nuclei with high mH2A levels in older animals.”
- Also stated in: § Expression of heterochromatic marks in murine tissues · plain
“the proportion of nuclei in the low and high expression groups changed with age, with an increased fraction of cells displaying higher levels of mH2A in the old animals”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
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- 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
“In contrast, only minimal changes in mH2A or HP1β mRNA levels were seen under any condition (Fig. S3).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in cultured fibroblasts
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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
“and an increase in mean staining intensity at old age.”
- Also stated in: § Expression of heterochromatic marks in murine tissues · plain
“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).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Abstract
plaindirect- 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.
- 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
“Mouse lung was characterized by monophasic mH2A expression histograms at both ages”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Abstract
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“Careful examination of several human, primate and murine tissues failed to demonstrate SAHF-like foci”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in cultured fibroblasts
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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
“Age-associated increases in mH2A levels were also readily apparent in skeletal muscle (Fig. 6A).”
§ 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.
- 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.
- 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
“Examination of additional samples from 27 month old males confirmed that the increase in mH2A levels affects animals near their median lifespan as well as very old animals of both sexes.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in murine tissues
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In the paper
“As was the case with murine skeletal muscle, the distributions were clearly biphasic with distinct high and low intensity nuclei (Fig. 7B).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in primate tissues
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Similarly, mouse muscle shows very low frequencies of DDR-positive cells”
§ 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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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
“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).”
§ 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.
- Based: passes — The paper gives a reason why it holds.
- 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
“Examination of baboon skeletal muscle revealed strong age-associated trends (Fig. 7A).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in primate tissues
boostedcorrelational- 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.
- 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 contrast, we observe in old animals 60–100% of the cells (depending on the tissue) to display elevated mH2A levels.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“a finding that we subsequently extended to lung and skeletal muscle tissue”
§ 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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- Load-bearing: passes — The paper’s conclusions depend on it.
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- Rests on an assumption: mH2A and HP1β are constituents of heterochromatin.
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
“Elevated levels of mH2A were readily apparent in lung nuclei of 24 month old C57BL/6 females (Fig. 4A).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in murine tissues
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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.
None of the sources cited for this claim have been checked yet.
In the paper
“When stained for the senescence-associated β-galactosidase (SA-β-Gal) marker, the tissues examined here (lung, liver, dermis, skeletal muscle) show positive cells in the range of 2–5% (Dimri et al., 1995; Wang et al., 2009) (our data).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
What the sources say
- Not checked yetcites Dimri et al., 1995
- Not checked yetcites Wang et al., 2009
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Examination of lung nuclei, which are smaller and do not undergo polyploidization revealed the same phenomenon (Fig. 5B).”
§ 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.
- Based: passes — The paper gives a reason why it holds.
- 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
“Likewise, mH2A levels did not increase when assessed by immunoblotting and normalized to either DNA or H2B.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in murine tissues
plain- Asserted: passes — The authors put it forward as true.
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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
“the proportion of nuclei in the low and high expression groups changed with age, with an increased fraction of cells displaying higher levels of mH2A in the old animals (Fig. 6C).”
§ 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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In the paper
“The prominent pericentromeric heterochromatin found in these cells allowed us, however, to detect a clear increase of mH2A localization to this compartment”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: mH2A and HP1β are constituents of heterochromatin.
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
“Finally, using HP1β antibody in the immunofluorescence and imunoblotting assays showed the same trends and patterns for this antigen as seen with mH2A.”
§ 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
“the shift in the ratio of low to high intensity nuclei was very pronounced, changing more than 3-fold from 1.45 in the young animals to 0.44 in the old animals (Fig. 7C).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in primate tissues
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Immunoblotting analysis of total lung tissue extracts confirmed the age-associated increase of mH2A levels (Fig. 4C).”
§ 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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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
“Higher levels of mH2A in old animals were also confirmed by immunoblotting (data not shown).”
§ 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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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
“and 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 > Discussion
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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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
“A significant number of nuclei (approximately 40% in both mouse and baboon) displayed high mH2A levels even in young animals.”
§ 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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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“analysis of dermal fibroblasts in skin biopsies revealed a more subtle increase in mH2A levels (Fig. S4).”
§ 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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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Both age groups showed two distinct populations of nuclei with either low or high levels of mH2A, with relatively few nuclei falling in between, giving rise to biphasic histogram distributions (Fig. 6B).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in murine tissues
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“We did however observe a significant redistribution of mH2A within the nuclei of old animals (Fig 5A).”
§ 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.
- Based: passes — The paper gives a reason why it holds.
- 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
“We use the assay to demonstrate increased levels of the heterochromatin-associated proteins mH2A and HP1β in human fibroblasts during replicative senescence in culture”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“it is rapidly becoming apparent that it may be subject to extensive age-associated remodeling (Fraga et al., 2005; Sedivy et al., 2008).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Introduction
What the sources say
- Not checked yetcites Fraga et al., 2005
- Not checked yetcites Sedivy et al., 2008
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.
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 developed an immunofluorescence assay to quantitatively detect, at the single cell level, changes in the nuclear content of chromatin-associated proteins.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Abstract
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“No increase was seen in early passage cells rendered quiescent by contact inhibition and serum deprivation, indicating that the effect is not a general consequence of cell cycle arrest.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in cultured fibroblasts
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“our work, as well as other studies on single cells (Bahar et al., 2006), indicate that aging tissues are mosaics of normal cells with interspersed senescent (or otherwise age-compromised) cells.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Introduction
What the sources say
- Not checked yetcites Bahar et al., 2006
hedged- 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.
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
“These saturating concentrations were found to be at least 10-fold higher (Table S1) than typically recommended in standard immunofluorescence assays.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in cultured fibroblasts
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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 frequencies of cells displaying evidence of increased heterochromatinization are too high to be readily accounted for by replicative or oncogene-induced cellular senescence”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Abstract
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“skeletal muscle also displays very marginal age-asssociated upregulation of p16 (Edwards et al., 2007)”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
What the sources say
- Not checked yetcites Edwards et al., 2007
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“Our data are indicative of increasing concentrations of mH2A in regions of constitutive heterochromatin”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in murine tissues
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.
- Rests on an assumption: The anti-centromere autoantibody used to verify pericentromeric localization recognizes mouse centromeres specifically.
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 pericentromeric localization of the mH2A foci was verified using a human anti-centromere autoantibody.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in murine tissues
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The anti-centromere autoantibody used to verify pericentromeric localization recognizes mouse centromeres specifically.
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
“we believe it is reasonable to conclude that SAHF do not accumulate with aging in vivo, at least as morphologically distinct structures that can be visualized by microscopy in mouse or baboon.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Several lines of evidence suggest that this is unlikely to be the whole story.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
hedged- 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.
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 is thus unlikely that the mature myocytes with high mH2A levels are senescent, at least using our current definitions and understanding of cellular senescence.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
hedged- 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.
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 this communication we describe the development of an assay, based on immunofluorescence microscopy, capable of quantitatively detecting, at the single cell level, changes in the nuclear content of chromatin associated proteins.”
§ 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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In the paper
“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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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“While the DDR-positive cells may be senescent, we consider it unlikely that all of the mH2A-positive cells are senescent.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
hedged- 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.
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 is also evident that the majority of normal cells in the lung without any evidence of DDR display elevated mH2A levels with age.”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Discussion
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.
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 correlation between the fold-change increase observed by the immunoblotting and immunofluorescence methods was excellent (Fig. 4D).”
§ Age-associated increase in heterochromatic marks in murine and primate tissues > Results > Expression of heterochromatic marks in murine tissues
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The quote only partly states this claim. 3
- It may state two separate claims as one. 26
- Probably not a substantial claim. 19
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
“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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- Load-bearing: passes — The paper’s conclusions depend on it.
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The quote only partly states this claim.
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
“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
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.
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
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
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
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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 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
“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
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.
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.
- 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. The quote only partly states this claim.
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
“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.
- 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: 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.
- 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: 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.
- 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: 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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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 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
“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.
- 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 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.
- 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 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 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.
- 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: 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
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. 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
“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
boostedcorrelational- 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.
None of the sources cited for this claim have been checked yet.
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.
- 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.
None of the sources cited for this claim have been checked yet.
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.
- 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
“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.
- 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
“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
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.
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
“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
plaindirect- 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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
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
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.
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.
- 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.
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 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
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.
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.
- 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.
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
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. 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
“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.
- 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.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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.
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.
- 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.
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.
- 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
“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.
- 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.
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.
- Based: passes — The paper gives a reason why it holds.
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.
- Based: passes — The paper gives a reason why it holds.
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).”
Citations
Cites
Jenuwein, T., & Allis, C. D. (2001) · Science · doi:10.1126/science.1063127 · Cited by 9,756
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
Extension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975
Epigenetic differences arise during the lifetime of monozygotic twins
Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., Heine-Suñer, D., Cigudosa, J. C., Urioste, M., Benitez, J., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500398102 · Cited by 3,602
The complex language of chromatin regulation during transcription
Berger, S. L. (2007) · Nature · doi:10.1038/nature05915 · Cited by 2,768
Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
Narita, M., Nuñez, S., Heard, E., Narita, M., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., & Lowe, S. W. (2003) · Cell · doi:10.1016/s0092-8674(03)00401-x · Cited by 2,278 · cited 4×
“…high intensity staining with general DNA dyes such as DAPI, and subsequently as foci of immunofluorescent staining with a variety of antibodies against components or marks of heterochromatin, such as HP1a, b or c, mH2A, H3K9Me2, etc. (Narita et al., 2003; Zhang et al., 2005; Funayama et al., 2006).”
BackgroundInfluentialOncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
Bartkova, J., Rezaei, N., Liontos, M., Karakaidos, P., Kletsas, D., Issaeva, N., Vassiliou, L.-V. F., Kolettas, E., Niforou, K., Zoumpourlis, V. C., et al. (2006) · Nature · doi:10.1038/nature05268 · Cited by 1,986
Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication
Di Micco, R., Fumagalli, M., Cicalese, A., Piccinin, S., Gasparini, P., Luise, C., Schurra, C., Garre’, M., Giovanni Nuciforo, P., Bensimon, A., et al. (2006) · Nature · doi:10.1038/nature05327 · Cited by 1,821
Cellular senescence in cancer and aging.
Collado, M., Blasco, M. A., & Serrano, M. (2007) · Cell · doi:10.1016/j.cell.2007.07.003 · Cited by 1,708
Cited by
Sorted by citations
L1 drives IFN in senescent cells and promotes age-associated inflammation
De Cecco, M., Ito, T., Petrashen, A. P., Elias, A. E., Skvir, N. J., Criscione, S. W., Caligiana, A., Brocculi, G., Adney, E. M., Boeke, J. D., et al. (2019) · Nature · doi:10.1038/s41586-018-0784-9 · Cited by 1,255
“All microscope settings were set to collect images below saturation and were kept constant for all images taken in one experiment, as previously described 61 .”
Self-citationEpigenetic mechanisms of longevity and aging
Sen, P., Shah, P. P., Nativio, R., & Berger, S. L. (2016) · Cell · doi:10.1016/j.cell.2016.07.050 · Cited by 956
Pal, S., & Tyler, J. K. (2016) · Science Advances · doi:10.1126/sciadv.1600584 · Cited by 860
Jurk, D., Wang, C., Miwa, S., Maddick, M., Korolchuk, V., Tsolou, A., Gonos, E. S., Thrasivoulou, C., Jill Saffrey, M., Cameron, K., et al. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00870.x · Cited by 598
Lysosome-mediated processing of chromatin in senescence
Ivanov, A., Pawlikowski, J., Manoharan, I., van Tuyn, J., Nelson, D. M., Rai, T. S., Shah, P. P., Hewitt, G., Korolchuk, V. I., Passos, J. F., et al. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201212110 · Cited by 539
Self-citation
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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