The DOI matches its Crossref record; 101 of the 108 references it cites were found in a registry or an index, and 7 are not checked yet; 1 of the 101 sources its claims cite were checked for support.
Aging of hematopoietic stem cells
Open accessAbstract
Hematopoietic stem cells (HSCs) ensure a balanced production of all blood cells throughout life. As they age, HSCs gradually lose their self-renewal and regenerative potential, whereas the occurrence of cellular derailment strongly increases. Here we review our current understanding of the molecular mechanisms that contribute to HSC aging. We argue that most of the causes that underlie HSC aging result from cell-intrinsic pathways, and reflect on which aspects of the aging process may be reversible. Because many hematological pathologies are strongly age-associated, strategies to intervene in aspects of the stem cell aging process may have significant clinical relevance.
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51 Not checked yet · 23 Own interpretation · 1 Partly supported · accuracy not yet measured
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In the paper
“young bone marrow cells, when transplanted into aged recipients, engraft worse than when transplanted into young recipients.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Cell-intrinsic vs cell-extrinsic mechanisms
What the sources say
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In the paper
“the functional heterogeneity of the HSC population increases with age.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Heterogeneity of HSC aging
What the sources say
- Not checked yetcites [10] Dykstra, 2011, Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells, J Exp Med source
- Not checked yetcites [13] Sudo, 2000, Age-associated characteristics of murine hematopoietic stem cells, J Exp Med source
- Not checked yetcites [17] Beerman, 2010, Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion, Proc Natl Acad Sci USA source
- Not checked yetcites [32] Cho, 2008, A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells, Blood source
- Not checked yetcites [33] Ho, 2017, Autophagy maintains the metabolism and function of young and old stem cells, Nature source
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In the paper
“aging (also of the hematopoietic system) is at least qualitatively different in distinct strains of mice.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > HSC self-renewal and aging
What the sources say
- Not checked yetcites [30] De Haan, 1999, Genetic analysis of hemopoietic cell cycling in mice suggests its involvement in organismal life span, FASEB J source
- Not checked yetcites [31] de Haan, 1997, Intrinsic and extrinsic control of hemopoietic stem cell numbers: mapping of a stem cell gene, J Exp Med source
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In the paper
“hematological malignancies can result from a defective bone marrow environment.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Cell-intrinsic vs cell-extrinsic mechanisms
What the sources say
- Not checked yetcites [44] Zambetti, 2016, Mesenchymal inflammation drives genotoxic stress in hematopoietic stem cells and predicts disease evolution in human pre-leukemia, Cell Stem Cell source
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In the paper
“most of the proliferative burden resides with committed progenitors”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > HSC self-renewal and aging
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In the paper
“transplanting aged HSCs in a young environment apparently cannot reverse these changes.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Cell-intrinsic vs cell-extrinsic mechanisms
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In the paper
“in aged mice that display an overall increase in HSC pool size”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Heterogeneity of HSC aging
What the sources say
- Not checked yetcites [10] Dykstra, 2011, Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells, J Exp Med source
- Not checked yetcites [13] Sudo, 2000, Age-associated characteristics of murine hematopoietic stem cells, J Exp Med source
- Not checked yetcites [17] Beerman, 2010, Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion, Proc Natl Acad Sci USA source
- Not checked yetcites [32] Cho, 2008, A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells, Blood source
- Not checked yetcites [33] Ho, 2017, Autophagy maintains the metabolism and function of young and old stem cells, Nature source
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In the paper
“aged HSC accumulate signatures of widespread DNA damage, including g-H2AX foci.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > DNA damage
What the sources say
- Not checked yetcites [49] Walter, 2015, Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells, Nature source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“in healthy elderly individuals, DNA mutations in specific loci are associated with the establishment of clonal hematopoiesis”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > DNA damage
What the sources say
- Not checked yetcites [52] Steensma, 2015, Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes, Blood source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Mice, or patients for that matter, suffering from mutations in genes encoding for proteins involved in DNA repair display many aspects of premature stem cell aging.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > DNA damage
What the sources say
- Not checked yetcites [46] Ju, 2007, Telomere dysfunction induces environmental alterations limiting hematopoietic stem cell function and engraftment, Nat Med source
- Not checked yetcites [47] Rossi, 2007, Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age, Nature source
- Not checked yetcites [48] Alter, 2012, Telomere length is associated with disease severity and declines with age in dyskeratosis congenita, Haematologica source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“in mice with long telomeres, the inability to maintain telomere length is associated with severe HSC malfunctioning.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > DNA damage
What the sources say
- Not checked yetcites [54] Rudolph, 1999, Longevity, stress response, and cancer in aging telomerase-deficient mice, Cell source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Multiple molecular and cell-intrinsic mechanisms have been reported to contribute to the age-associated decline of HSC functioning”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Cell-intrinsic mechanisms that cause HSC aging
What the sources say
- Not checked yetcites [45] Geiger, 2013, The ageing haematopoietic stem cell compartment, Nat Rev Immunol source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“individual HSCs behave very differently.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Heterogeneity of HSC aging
What the sources say
- Not checked yetcites [10] Dykstra, 2011, Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells, J Exp Med source
- Not checked yetcites [13] Sudo, 2000, Age-associated characteristics of murine hematopoietic stem cells, J Exp Med source
- Not checked yetcites [17] Beerman, 2010, Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion, Proc Natl Acad Sci USA source
- Not checked yetcites [32] Cho, 2008, A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells, Blood source
- Not checked yetcites [33] Ho, 2017, Autophagy maintains the metabolism and function of young and old stem cells, Nature source
plain- Asserted: passes — The authors put it forward as true.
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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
“We argue that most of the causes that underlie HSC aging result from cell-intrinsic pathways”
- Also stated in: § Cell-intrinsic vs cell-extrinsic mechanisms · hedged
“That aged HSC are functionally impaired compared with their young counterparts upon transplantation in young mice strongly suggests that HSC aging manifests largely as a consequence of cell-intrinsic molecular changes.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Abstract
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- Also stated in: § Cell-intrinsic vs cell-extrinsic mechanisms · hedged
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In the paper
“That aged HSC are functionally impaired compared with their young counterparts upon transplantation in young mice”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Cell-intrinsic vs cell-extrinsic mechanisms
What the sources say
- Not checked yetcites [5] Harrison, 1982, Loss of stem cell repopulating ability upon transplantation. Effects of donor age, cell number, and transplantation procedure, J Exp Med source
- Not checked yetcites [10] Dykstra, 2011, Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells, J Exp Med source
- Not checked yetcites [11] Van Zant, 1990, Genotype-restricted growth and aging patterns in hematopoietic stem cell populations of allophenic mice, J Exp Med source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“the length of telomeres in HSC can be increased by enforced overexpression of telomerase, in mice this does not rescue functional impairment.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > DNA damage
What the sources say
- Not checked yetcites [55] Allsopp, 2003, Effect of TERT over-expression on the long-term transplantation capacity of hematopoietic stem cells, Nat Med source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“It seems highly likely that not all epigenetic moieties that are required to specify stem cell functioning are properly maintained after a stem cell has divided”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Epigenetic reprogramming
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“this study demonstrates that at least some aspects of the aging process appear to be reversible.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Polarity
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“but they do not show functional decline during normal aging.100”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Is stem cell aging similar in different tissues?
What the sources say
- Not checked yetcites [100] Barker, 2010, Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro, Cell Stem Cell source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The gradual and random erosion of epigenetic marks as stem cells divide and age, provides a conceptual framework which can explain why, at least in the mouse, stem cells can make only a very limited number of true self-renewal divisions.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Epigenetic reprogramming
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“A large fraction of aged HSCs show impaired levels of autophagy.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Impaired autophagy and mitochondrial activity
What the sources say
- Not checked yetcites [33] Ho, 2017, Autophagy maintains the metabolism and function of young and old stem cells, Nature source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“clonal hematopoiesis is a frequent event in elderly people.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Clonal hematopoiesis in human
What the sources say
- Not checked yetcites [74] Zink, 2017, Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly, Blood source
- Not checked yetcites [75] Xie, 2014, Age-related mutations associated with clonal hematopoietic expansion and malignancies, Nat Med source
- Not checked yetcites [76] Jaiswal, 2014, Age-related clonal hematopoiesis associated with adverse outcomes, N Engl J Med source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Epigenetic genes that are relatively frequently affected in these conditions include DNMT3A, EZH2, TET2, and SETDB1.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Epigenetic reprogramming
What the sources say
- Not checked yetcites [74] Zink, 2017, Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly, Blood source
- Not checked yetcites [75] Xie, 2014, Age-related mutations associated with clonal hematopoietic expansion and malignancies, Nat Med source
- Not checked yetcites [76] Jaiswal, 2014, Age-related clonal hematopoiesis associated with adverse outcomes, N Engl J Med source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“in many perfectly healthy very aged individuals, prominent clonal hematopoiesis is present without any signs of disease.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Clonal hematopoiesis in human
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“pharmacological targeting of senescent bone marrow cells has been shown to have beneficial effects.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Senescence
What the sources say
- Not checked yetcites [59] Chang, 2016, Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice, Nat Med source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In many tissues, irreversibly cell cycle-arrested senescent cells accumulate during normal aging.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Senescence
What the sources say
- Not checked yetcites [56] Childs, 2015, Cellular senescence in aging and age-related disease: from mechanisms to therapy, Nat Med source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“mice in which blood cell production is derived from even a single stem cell, are not necessarily prone to develop leukemia.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Clonal hematopoiesis in human
What the sources say
- Not checked yetcites [10] Dykstra, 2011, Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells, J Exp Med source
- Not checked yetcites [13] Sudo, 2000, Age-associated characteristics of murine hematopoietic stem cells, J Exp Med source
- Not checked yetcites [32] Cho, 2008, A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells, Blood source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Because the erosion of epigenetic marks is likely to be different for each stem cell, with age increased functional cell-to-cell variability is expected to develop.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Epigenetic reprogramming
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“it is not difficult to see how an accumulation of aberrant epigenetic marks could readily but gradually lead to loss of stem cell potential.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Epigenetic reprogramming
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, with time, in the bone marrow cells in which these self-renewal-enhancing mutations have occurred are expected to expand clonally.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Molecular reversibility low
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Intestinal stem cells do, as expected, accumulate random DNA damage, 99”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Is stem cell aging similar in different tissues?
What the sources say
- Not checked yetcites [99] Blokzijl, 2016, Tissue-specific mutation accumulation in human adult stem cells during life, Nature source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In fact, in comparing intestinal stem cells with those of the hematopoietic system, it appears as if aging is very different in these 2 tissues.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Is stem cell aging similar in different tissues?
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“cellular metabolism, controlled by mitochondrial status and reactive oxygen species and mTOR signaling, play an important role in maintaining HSC function throughout life”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Impaired autophagy and mitochondrial activity
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“This suggests that putative senescent cells in the bone marrow may secrete factors that negatively affect HSC potential.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Senescence
hedgedconditional- Asserted: passes — The authors put it forward as true.
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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
“that age-dependent clonal hematopoiesis is associated with disease suggests that, at least in these individuals, there may be a causal relationship.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Clonal hematopoiesis in human
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“reducing mitochondrial stress in aged HSCs can reverse loss of stem functioning.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Impaired autophagy and mitochondrial activity
What the sources say
- Not checked yetcites [62] Mohrin, 2015, Stem cell aging. A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging, Science source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“perturbation of a large number of epigenetic writers or erasers severely affects HSC function.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Epigenetic reprogramming
What the sources say
- Not checked yetcites [64] Kamminga, 2006, The polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion, Blood source
- Not checked yetcites [65] Iwama, 2004, Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1, Immunity source
- Not checked yetcites [66] Lessard, 1999, Functional antagonism of the polycomb-group genes eed and Bmi1 in hemopoietic cell proliferation, Genes Dev source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Whereas in the hematopoietic system, stem cell turnover is very low, proliferation rates in the intestine are very high.98”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Is stem cell aging similar in different tissues?
What the sources say
- Not checked yetcites [98] Clevers, 2013, The intestinal crypt, a prototype stem cell compartment, Cell source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“That subjects with clonal hematopoiesis are more susceptible to develop nonhematological, most notably cardiovascular, disease”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Clonal hematopoiesis in human
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“studies in mice have revealed that (enforced) altered expression of wild-type or mutant epigenetic writers affects self-renewal of HSCs.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Molecular reversibility low
What the sources say
- Not checked yetcites [64] Kamminga, 2006, The polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion, Blood source
- Not checked yetcites [68] Klauke, 2013, Polycomb Cbx family members mediate the balance between haematopoietic stem cell self-renewal and differentiation, Nat Cell Biol source
- Not checked yetcites [78] Mayle, 2015, Dnmt3a loss predisposes murine hematopoietic stem cells to malignant transformation, Blood source
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.
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, oligo-or even monoclonality is in and of itself not a (preclinical) sign of pathology.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Clonal hematopoiesis in human
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.
None of the sources cited for this claim have been checked yet.
In the paper
“during aging, blood cells are derived from fewer and fewer stem cells.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Clonal hematopoiesis in human
What the sources say
- Not checked yetcites [79] Busque, 1996, Nonrandom X-inactivation patterns in normal females: lyonization ratios vary with age, Blood source
- Not checked yetcites [80] Champion, 1997, Clonal haemopoiesis in normal elderly women: implications for the myeloproliferative disorders and myelodysplastic syndromes, Br J Haematol source
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.
In the paper
“In the intestine, progenitors have been shown to be able to revert to a stem cell fate, 101”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Is stem cell aging similar in different tissues?
What the sources say
- Not checked yetcites [101] Tetteh, 2016, Replacement of lost Lgr5-positive stem cells through plasticity of their enterocyte-lineage daughters, Cell Stem Cell source
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.
In the paper
“Whereas in the hematopoietic system, stem cell turnover is very low, proliferation rates in the intestine are very high.98”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Is stem cell aging similar in different tissues?
What the sources say
- Not checked yetcites [98] Clevers, 2013, The intestinal crypt, a prototype stem cell compartment, Cell source
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.
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
“suggests that these mutations also affect the functioning of fully differentiated cells, such as monocytes and macrophages.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Clonal hematopoiesis in human
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.
None of the sources cited for this claim have been checked yet.
In the paper
“In young mice, the pool of stem cells is small, but the potency of each stem cell is high.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Future perspectives
What the sources say
- Not checked yetcites Van Zant et al24
- Not checked yetcites Jung et al.25 Jung, 2017, Do hematopoietic stem cells get old?, Leukemia source
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.
In the paper
“In mice, the most primitive HSC are believed to cycle only once every ;4 months.23”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Future perspectives
What the sources say
- Not checked yetcites [23] Bernitz, 2016, Hematopoietic stem cells count and remember self-renewal divisions, Cell source
hedged- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“In young mice, the pool of stem cells is small, but the potency of each stem cell is high.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Future perspectives
What the sources say
- Not checked yetcites Van Zant et al24
- Not checked yetcites Jung et al.25 Jung, 2017, Do hematopoietic stem cells get old?, Leukemia source
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.
None of the sources cited for this claim have been checked yet.
In the paper
“enforced expression of transcription factors or microRNAs has been shown to be able to generate transplantable stem cells from committed cell types.[102][103][104]”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Is stem cell aging similar in different tissues?
What the sources say
- Not checked yetcites [102] Riddell, 2014, Reprogramming committed murine blood cells to induced hematopoietic stem cells with defined factors [published correction appears in Cell. 2014;158(1):226], Cell source
- Not checked yetcites [103] Pereira, 2013, Induction of a hemogenic program in mouse fibroblasts, Cell Stem Cell source
- Not checked yetcites [104] Wojtowicz, 2016, Ectopic miR-125a expression induces long-term repopulating stem cell capacity in mouse and human hematopoietic progenitors, Cell Stem Cell source
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.
In the paper
“In fact, reversal of some aging phenotypes has been achieved by reprogramming old HSCs to pluripotency and subsequently generating definitive hematopoiesis from these induced pluripotent stem cells.107”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Future perspectives
What the sources say
- Not checked yetcites [107] Wahlestedt, 2017, Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate, Nat Commun source
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.
In the paper
“Studies in other tissues have demonstrated that at least delaying components of the aging process can be a viable strategy, 106”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Future perspectives
What the sources say
- Not checked yetcites [106] Goodell, 2015, Stem cells and healthy aging, Science source
boostedconditional- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“In aged mice, the pool of stem cells has expanded, but their functionality is restricted.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Future perspectives
What the sources say
- Not checked yetcites Van Zant et al24
- Not checked yetcites Jung et al.25 Jung, 2017, Do hematopoietic stem cells get old?, Leukemia source
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.
In the paper
“Also, there is some evidence (but not a lot) that the same oncogenic mutation results in a more aggressive disease in aged stem cells compared with young cells.105”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Future perspectives
What the sources say
- Not checked yetcites [105] Signer, 2007, Age-related defects in B lymphopoiesis underlie the myeloid dominance of adult leukemia, Blood source
hedgeddirect- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Cellcycle times decrease with developmental stage.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Future perspectives
What the sources say
- Not checked yetcites Van Zant et al24
- Not checked yetcites Jung et al.25 Jung, 2017, Do hematopoietic stem cells get old?, Leukemia source
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.
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
“In this respect, it is interesting that another important difference between blood and gut is the extent to which plasticity occurs in progenitor cells in these respective tissues.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Is stem cell aging similar in different 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: During steady-state in vivo hematopoiesis, no conversion of hematopoietic progenitors into stem cells has been reported.
None of the sources cited for this claim have been checked yet.
In the paper
“In aged mice, the pool of stem cells has expanded, but their functionality is restricted.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Future perspectives
What the sources say
- Not checked yetcites Van Zant et al24
- Not checked yetcites Jung et al.25 Jung, 2017, Do hematopoietic stem cells get old?, Leukemia source
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.
None of the sources cited for this claim have been checked yet.
In the paper
“With each cell division, daughter cells lose developmental (long-term repopulating) potential, such that each daughter is less potent than its ancestor.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Future perspectives
What the sources say
- Not checked yetcites Van Zant et al24
- Not checked yetcites Jung et al.25 Jung, 2017, Do hematopoietic stem cells get old?, Leukemia source
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. 14
- Probably not a substantial claim. 4
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The genetic or pharmacological depletion of senescent cells in mice has been shown to enhance regenerative potential and extend life span.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Senescence
What the sources say
- Partly supportedcites [57] Baker, 2016, Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan, Nature sourceExperimental — accuracy not yet measured
The Discussion reports that clearing p16Ink4a-positive cells with the INK-ATTAC system extended median lifespan in mice. The fat-progenitor results show preservation of adipogenesis-related measures, but not a general increase in regenerative potential; Extended Data Figure 10 reports that clearance during wound healing delayed wound closure. The study used a drug to activate a genetic clearance system, rather than demonstrating a separate pharmacological depletion method. (LLM, conf=0.88)
boosteddirect- 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.
- Partly supported
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 pool of stem cells with reduced potential increases to compensate for loss of function of individual stem cells”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > HSC self-renewal and aging
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“the involvement of telomere shortening in the functional decline of HSC is particularly evident in human”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > DNA damage
What the sources say
- Not checked yetcites [53] Aubert, 2008, Telomeres and aging, Physiol Rev source
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 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
“Although some of these cell-intrinsic causes of aging are unlikely to be reversible, several others might allow interventions and thus could potentially be explored for pharmacological targeting”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Cell-intrinsic mechanisms that cause HSC aging
hedgedconditional- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“an age-dependent increase in the frequency of putative stem cells, coinciding with impaired functionality and reduced lymphoid potential, has also been in the human system.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > HSC self-renewal and aging
What the sources say
- Not checked yetcites [27] Kuranda, 2011, Age-related changes in human hematopoietic stem/progenitor cells, Aging Cell source
- Not checked yetcites [28] Pang, 2011, Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age, Proc Natl Acad Sci USA source
- Not checked yetcites [29] Rundberg Nilsson, 2016, Human and murine hematopoietic stem cell aging is associated with functional impairments and intrinsic megakaryocytic/erythroid bias, PLoS One source
hedgedcorrelational- 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.
In the paper
“telomeres progressively shorten in human HSCs isolated from fetal liver, cord blood, or adult bone marrow, which is associated with a strongly reduced proliferative potential.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > HSC self-renewal and aging
What the sources say
- Not checked yetcites [26] Vaziri, 1994, Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age, Proc Natl Acad Sci USA source
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.
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
“with each cell division, the potential of a HSC to contribute to blood cell production declines”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > HSC self-renewal and aging
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“during steady-state hematopoiesis the most primitive stem cells are largely inactive.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > HSC self-renewal and aging
What the sources say
- Not checked yetcites [18] Van Zant, 1984, Studies of hematopoietic stem cells spared by 5-fluorouracil, J Exp Med source
- Not checked yetcites [19] Bradford, 1997, Quiescence, cycling, and turnover in the primitive hematopoietic stem cell compartment, Exp Hematol
- Not checked yetcites [20] Cheshier, 1999, In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells, Proc Natl Acad Sci USA source
- Not checked yetcites [21] Dykstra, 2007, Long-term propagation of distinct hematopoietic differentiation programs in vivo, Cell Stem Cell source
- Not checked yetcites [22] Morita, 2010, Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment, J Exp Med source
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
“in effect they are likely to be highly interdependent and interconnected.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Cell-intrinsic mechanisms that cause HSC aging
hedgedcorrelational- 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 most irreversible cause of HSC aging relates to the accumulation of random DNA damage.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > DNA damage
plaindirect- Asserted: fails — The authors may not 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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“clonal hematopoiesis in otherwise healthy individuals increases the risk to develop leukemia, and, interestingly, cardiovascular disease, and thus is associated with increased mortality.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Clonal hematopoiesis in human
What the sources say
- Not checked yetcites [74] Zink, 2017, Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly, Blood source
- Not checked yetcites [75] Xie, 2014, Age-related mutations associated with clonal hematopoietic expansion and malignancies, Nat Med source
- Not checked yetcites [76] Jaiswal, 2014, Age-related clonal hematopoiesis associated with adverse outcomes, N Engl J Med source
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.
None of the sources cited for this claim have been checked yet.
In the paper
“clonal hematopoiesis has been associated with increased incidence of atherosclerotic cardiovascular disease, suggesting that the function of monocytic cells derived from these aged stem cell clones is impaired.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Clonal hematopoiesis in human
What the sources say
hedgedcorrelational- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“high levels of reactive oxygen species, generated by mitochondria, accumulate in aged HSCs and compromise their functioning.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Impaired autophagy and mitochondrial activity
What the sources say
- Not checked yetcites [61] Ito, 2006, Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells, Nat Med source
- Not checked yetcites [62] Mohrin, 2015, Stem cell aging. A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging, Science source
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.
In the paper
“aged red cells and aged platelets display impaired functioning”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Clonal hematopoiesis in human
What the sources say
- Not checked yetcites [82] Hoehn, 2015, Molecular mechanisms of erythrocyte aging, Biol Chem source
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 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
“impaired autophagy in aged HSCs appears to specifically result in the accumulation of mitochondria, which in turn induces metabolic stress.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Impaired autophagy and mitochondrial activity
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
“pharmacological interventions in these signaling pathways are feasible and may be exploited to restore function in aged HSCs.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Impaired autophagy and mitochondrial activity
hedgedconditional- 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
“mutations in genes encoding for epigenetic enzymes have been found in either elderly people whose hematopoietic system has become oligoclonal, or in patients with myelodysplastic syndromes or acute myeloid leukemia.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Epigenetic reprogramming
What the sources say
- Not checked yetcites [52] Steensma, 2015, Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes, Blood source
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.
It may state two separate claims as one.
In the paper
“Mitochondrial dysfunctioning caused by accumulating mitochondrial DNA mutations has been shown to cause multiple hematopoietic defects that are typically seen in the elderly, but HSCs themselves appear to relatively resistant.”
§ HEMATOLOGIC DISEASE AT OLDER AGE Aging of hematopoietic stem cells > Impaired autophagy and mitochondrial activity
What the sources say
- Not checked yetcites [63] Norddahl, 2011, Accumulating mitochondrial DNA mutations drive premature hematopoietic aging phenotypes distinct from physiological stem cell aging, Cell Stem Cell source
hedgeddirect- 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.
The paper relies on this without support.
The formation of blood cells in mice and humans is conceptually identical.
“decades of research have shown that, conceptually, the formation of blood cells in mouse and human is identical”
The paper relies on this without support.
Many hematological conditions are strongly age-dependent.
“many hematological conditions are strongly age-dependent.”
The paper relies on this without support.
The purity of HSCs in transplantation experiments is never more than 50%.
“the purity of HSCs, at least when assayed in transplantation experiments, is never more than 50%.”
The paper relies on this without support.
Even after the most stringent enrichment protocols, many non-HSCs remain.
“even after the most stringent enrichment protocols, many non-HSCs (mostly progenitors) remain.”
The paper relies on this without support.
Genetic disparities are likely to be prominent in humans.
“These genetic disparities are also likely to be prominent in human.”
The paper relies on this without support.
During steady-state in vivo hematopoiesis, no conversion of hematopoietic progenitors into stem cells has been reported.
“but in the hematopoietic system such progenitor-to-stem cell conversions have never been described, at least not during steadystate in vivo hematopoiesis.”
The authors state this as an assumption.
Human HSC aging is not fundamentally different from mouse HSC aging.
“Assuming that in human HSC aging is not fundamentally different than in mice”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, aged HSCs have been shown to have lower regenerative potential and skewed differentiation toward the myeloid lineage instead of the lymphoid lineage [88].”
From Osteoimmunology of Fracture Healing. (2024) · cites this paper as [88]
Citations
Cites
1 retracted
Systemic signals regulate ageing and rejuvenation of blood stem cell niches
Mayack, S. R., Shadrach, J. L., Kim, F. S., & Wagers, A. J. (2010) · Nature · doi:10.1038/nature08749 · Cited by 137
RetractedLópez-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982
Age-related clonal hematopoiesis associated with adverse outcomes
Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P. V., Mar, B. G., Lindsley, R. C., Mermel, C. H., Burtt, N., Chavez, A., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408617 · Cited by 4,841
Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence
Genovese, G., Kähler, A. K., Handsaker, R. E., Lindberg, J., Rose, S. A., Bakhoum, S. F., Chambert, K., Mick, E., Neale, B. M., Fromer, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1409405 · Cited by 3,531
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,876
Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease
Jaiswal, S., Natarajan, P., Silver, A. J., Gibson, C. J., Bick, A. G., Shvartz, E., McConkey, M., Gupta, N., Gabriel, S., Ardissino, D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1701719 · Cited by 2,683
Cellular senescence in aging and age-related disease: from mechanisms to therapy
Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015) · Nature Medicine · doi:10.1038/nm.4000 · Cited by 2,363
Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes
Steensma, D. P., Bejar, R., Jaiswal, S., Lindsley, R. C., Sekeres, M. A., Hasserjian, R. P., & Ebert, B. L. (2015) · Blood · doi:10.1182/blood-2015-03-631747 · Cited by 1,971
Age-related mutations associated with clonal hematopoietic expansion and malignancies
Xie, M., Lu, C., Wang, J., McLellan, M. D., Johnson, K. J., Wendl, M. C., McMichael, J. F., Schmidt, H. K., Yellapantula, V., Miller, C. A., et al. (2014) · Nature Medicine · doi:10.1038/nm.3733 · Cited by 1,874
Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., Janakiraman, K., Sharpless, N. E., Ding, S., Feng, W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4010 · Cited by 1,819
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Haematopoietic stem cell activity and interactions with the niche
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Measuring biological aging in humans: a quest
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Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation
Wilkinson, A. C., Ishida, R., Kikuchi, M., Sudo, K., Morita, M., Crisostomo, R. V., Yamamoto, R., Loh, K. M., Nakamura, Y., Watanabe, M., et al. (2019) · Nature · doi:10.1038/s41586-019-1244-x · Cited by 411
TGF-β Signaling in Cellular Senescence and Aging-Related Pathology
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Metadata
- Authors
- de Haan, G., & Lazare, S. S.
- Affiliations
- European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- University Medical Center Groningen (NL)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2018-02-01
- Volume
- 131
- Issue
- 5
- Pages
- 479-487
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2768409010
- Semantic Scholar
- 767a7a803b0d377cfb03d909da859be3e4df29bc
- Cited by
- 432
- References
- 107
- Citations by year
- 2026: 41 · 2025: 46 · 2024: 68 · 2023: 62 · 2022: 55 · 2021: 67 · 2020: 51 · 2019: 27 · 2018: 15
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- European Commission (316964)
- ZonMw
- KWF Kankerbestrijding (2014-7178, RUG 2014-7178)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Keywords
- hematopoietic stem cells, stem cell aging, cellular senescence, self-renewal, regenerative capacity, molecular mechanisms of aging
- MeSH terms
- Aging, Animals, Autophagy, Hematopoiesis, Hematopoietic Stem Cells, Humans, Mitochondria, Cellular Senescence, Epigenesis, Genetic
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).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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