The DOI matches its Crossref record; 46 of the 47 references it cites were found in a registry or an index.
Cell intrinsic alterations underlie hematopoietic stem cell aging
Open accessAbstract
Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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
“The age-related increase in expression of myeloid lineage genes in the studies noted above (11,17) likely resulted from the accumulation of myeloid-biased HSCs, as these analyses were performed on unseparated pools of HSCs.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [11]
In the citing paper
“This shift has been correlated with increased expression of myeloid lineage genes and downregulation of those specifying a lymphoid lineage fate (11,17).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [11]
In the citing paper
“The causes of this age-related reduction in lymphocyte development are multifactorial and include changes in HSCs and progenitor cells (11,12) as well as the local tissue and systemic environments (13,14).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [11]
In the citing paper
“From an immunologic perspective, the most profound effect of stem cell aging in both mice (11,18) and humans (17) is a decreased capacity to produce lymphocytes and an increase in myeloid potential.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [11]
In the citing paper
“young bone marrow cells, when transplanted into aged recipients, engraft worse than when transplanted into young recipients.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [12]
In the citing paper
“examination of donor-derived reconstitution from old HSCs was significantly lower compared to the young with a marked myeloid bias lineage output”
From Quiescent Hematopoietic Stem Cells Accumulate DNA Damage during Aging that Is Repaired upon Entry into Cell Cycle (2014) · cites this paper as Rossi et al., 2005
Citations
Cites
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219
Stem cells, cancer, and cancer stem cells
Reya, T., Morrison, S. J., Clarke, M. F., & Weissman, I. L. (2001) · Nature · doi:10.1038/35102167 · Cited by 9,738
Self-citationModel-based analysis of oligonucleotide arrays: Expression index computation and outlier detection.
Li, C., & Wong, W. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.1.31 · Cited by 3,133
Purification and Characterization of Mouse Hematopoietic Stem Cells
Spangrude, G. J., Heimfeld, S., & Weissman, I. L. (1988) · Science · doi:10.1126/science.2898810 · Cited by 2,908
Self-citationIsolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.
Goodell, M. A., Brose, K., Paradis, G. A., Conner, A. N., & Mulligan, R. C. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.4.1797 · Cited by 2,902
A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
Akashi, K., Traver, D., Miyamoto, T., & Weissman, I. L. (2000) · Nature · doi:10.1038/35004599 · Cited by 2,617
Self-citationIdentification of Clonogenic Common Lymphoid Progenitors in Mouse Bone Marrow
Kondo, M., Weissman, I. L., & Akashi, K. (1997) · Cell · doi:10.1016/s0092-8674(00)80453-5 · Cited by 2,253
Self-citationLong-Term Lymphohematopoietic Reconstitution by a Single CD34-Low/Negative Hematopoietic Stem Cell
Osawa, M., Hanada, K., Hamada, H., & Nakauchi, H. (1996) · Science · doi:10.1126/science.273.5272.242 · Cited by 2,141
Gene regulation and DNA damage in the ageing human brain
Lu, T., Pan, Y., Kao, S.-Y., Li, C., Kohane, I., Chan, J., & Yankner, B. A. (2004) · Nature · doi:10.1038/nature02661 · Cited by 1,874
Flagged first, then by citations
1 of the 47 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Yang, L., Bryder, D., Adolfsson, J., Nygren, J., Mansson, R., Sigvardsson, M. & Jacobsen, S. E. (2004) Blood 105, 2717-2723.15572596
Cited by
Sorted by citations
Items 301–400 of 999
Spyridopoulos, I., Erben, Y., Brümmendorf, T. H., Haendeler, J., Dietz, K., Seeger, F. H., Kissel, C. K., Martin, H., Hoffmann, J., Aßmus, B., et al. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.160846 · Cited by 68
Cellular senescence in lymphoid organs and immunosenescence
Budamagunta, V., Foster, T. C., & Zhou, D. (2021) · Aging · doi:10.18632/aging.203405 · Cited by 73
Ainciburu, M., Ezponda, T., Berastegui, N., Piérola, A. A., Vilas‐Zornoza, A., Martín‐Úriz, P. S., Alignani, D., Lamo-Espinosa, J. M., San-Julián, M., Jiménez, T., et al. (2023) · eLife · doi:10.7554/elife.79363 · Cited by 68
Clonal tracing with somatic epimutations reveals dynamics of blood ageing
Scherer, M., Singh, I., Braun, M. M., Szu‐Tu, C., Sánchez-Sánchez, P., Lindenhofer, D., Jakobsen, N. A., Körber, V., Kardorff, M., Nitsch, L., et al. (2025) · Nature · doi:10.1038/s41586-025-09041-8 · Cited by 81
Blagosklonny, M. V. (2008) · Rejuvenation Research · doi:10.1089/rej.2008.0722 · Cited by 66
“2,21 With age, neural crest stem cells in the adult gut loose their responsiveness to lineage determination factors.”
Muthná, D., Soukup, T., Vávrová, J., Mokrý, J., Ćmielová, J., Víšek, B., Mrkvicová, A., Havelek, R., Suchánek, J., Filip, S., et al. (2010) · Stem Cells and Development · doi:10.1089/scd.2009.0449 · Cited by 66
“Long-term cultivated non-irradiated DPSCs were seem to result from or cause activation of genes that respond to stress, infl ammatory, or DNA repair response typical for aged somatic cells [ 7 ].”
Oduro, K. A., Liu, F., Tan, Q., Kim, C. K., Lubman, O., Fremont, D. H., Mills, J. C., & Choi, K. (2012) · Blood · doi:10.1182/blood-2011-11-391342 · Cited by 65
Ruple, A., MacLean, E. L., Snyder‐Mackler, N., Creevy, K. E., & Promislow, D. (2021) · Annual Review of Animal Biosciences · doi:10.1146/annurev-animal-051021-080937 · Cited by 77
Nitta, E., Yamashita, M., Hosokawa, K., Xian, M., Takubo, K., Arai, F., Nakada, S., & Suda, T. (2011) · Blood · doi:10.1182/blood-2010-08-297390 · Cited by 64
Sirtuin 1, stem cells, aging, and stem cell aging
Mantel, C., & Broxmeyer, H. E. (2008) · Current Opinion in Hematology · doi:10.1097/moh.0b013e3283043819 · Cited by 65
Latchney, S. E., & Calvi, L. M. (2016) · Seminars in Hematology · doi:10.1053/j.seminhematol.2016.10.001 · Cited by 70
“There is a collective downregulation of lymphoid genes along with an upregulation of myeloid genes, such as runt-related transcription factor 1 (Runx1), Hoxb6, and Osmr in aged HSCs [76].”
BackgroundSun, Z., Li, F., Zhou, X., Chung, K. F., Wang, W., & Wang, J. (2018) · Journal of Thoracic Disease · doi:10.21037/jtd.2018.01.46 · Cited by 64
“Function of HPCs were also reported to decline during aging (82-84).”
BackgroundGeiger, H., Denkinger, M. D., & Schirmbeck, R. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.05.002 · Cited by 66
“Xing Z, Ryan MA, Daria D, Nattamai KJ, Van Zant G, Wang L, Zheng Y, Geiger H: Increased hematopoietic stem cell mobilization in aged mice.”
InfluentialLouis, I., Heinonen, K. M., Chagraoui, J., Vainio, S. J., Sauvageau, G., & Perreault, C. (2008) · Immunity · doi:10.1016/j.immuni.2008.04.023 · Cited by 62
Immunosenescence and organ transplantation
Heinbokel, T., Elkhal, A., Liu, G., Edtinger, K., & Tullius, S. G. (2013) · Transplantation Reviews · doi:10.1016/j.trre.2013.03.001 · Cited by 65
“At the same time, an up-regulation of genes involved in myeloid specification and function is observed [37].”
Aging and erythropoiesis: Current state of knowledge
Price, E. A. (2008) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2008.04.005 · Cited by 64
Cellular Memory and Hematopoietic Stem Cell Aging
Kamminga, L. M., & de Haan, G. (2006) · Stem Cells · doi:10.1634/stemcells.2005-0345 · Cited by 63
The crossroads between cancer stem cells and aging
Franco, S. S., Raveh-Amit, H., Kobolák, J., Al-Qahtani, M. H., Mobasheri, A., & Dinnyés, A. (2015) · BMC Cancer · doi:10.1186/1471-2407-15-s1-s1 · Cited by 63
“This relationship is supported by the expression of leukaemia-related genetic [95] and epigenetic alterations [100] in aged HSCs, associated with an aged bone marrow microenvironment that allows the expansion of LSCs [97].”
BackgroundInfluentialSimonnet, A., Nehmé, J., Vaigot, P., Barroca, V., Leboulch, P., & Roux, D. T. (2009) · Stem Cells · doi:10.1002/stem.66 · Cited by 66
The Fountain of Youth: A tale of parabiosis, stem cells, and rejuvenation
Conese, M., Carbone, A., Beccia, E., & Angiolillo, A. (2017) · Open Medicine · doi:10.1515/med-2017-0053 · Cited by 65
“As with HSCs, both the frequency and total number of osteoblastic niche cells isolatable from aged mice were increased compared to young controls.”
BackgroundResultInfluentialKidney transplantation and the ageing immune system
McKay, D. B., & Jameson, J. (2012) · Nature Reviews Nephrology · doi:10.1038/nrneph.2012.242 · Cited by 62
Concise Review: Hematopoietic Stem Cell Aging, Life Span, and Transplantation
Zant, G. E. V., & Liang, Y. (2012) · Stem Cells Translational Medicine · doi:10.5966/sctm.2012-0033 · Cited by 62
Gutierrez-Martinez, P., Hogdal, L., Nagai, M., Kruta, M., Singh, R., Sarosiek, K., Nussenzweig, A., Beerman, I., Letai, A., & Rossi, D. J. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0054-y · Cited by 60
Self-citationAging of the Hematopoietic Stem Cell Niche: New Tools to Answer an Old Question
Matteini, F., Mulaw, M. A., & Florian, M. C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.738204 · Cited by 60
“In particular in the BM, upon aging the HSC pool is expanded, and HSCs display a skewed differentiation to myeloid progenitors (50) at the expense of the lymphoid ones (51) and an impaired regenerative potential (51).”
BackgroundCellular Mechanisms of Somatic Stem Cell Aging
Jung, Y., & Brack, A. S. (2014) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/b978-0-12-416022-4.00014-7 · Cited by 63
“…skewed differentiation potential toward the myeloid lineage at the expense of the lymphoid and erythroid lineages (Beerman, Bhattacharya, et al., 2010; Benz et al., 2012; Challen et al., 2010; Dykstra, Olthof, Schreuder, Ritsema, & de Haan, 2011; Morita, Ema, & Nakauchi, 2010; Rossi et al., 2005).”
BackgroundReduced EBF expression underlies loss of B‐cell potential of hematopoietic progenitors with age
Lescale, C., Dias, S., Maës, J., Cumano, A., Szabo, P., Charron, D. J., Weksler, M. E., Dosquet, C., Vieira, P., & Goodhardt, M. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00566.x · Cited by 63
“, 2008), including an increase in the number of HSC in several mouse strains, increased self-renewal activity and a per cell decrease in the homing and reconstituting efficiency of HSC from old mice (Morrison et al., 1996; Sudo et al., 2000; Liang et al., 2005; Rossi et al., 2005; Pearce et al., 2007).”
BackgroundResultInfluentialThe Ets Transcription Factor EHF as a Regulator of Cornea Epithelial Cell Identity
Stephens, D. N., Klein, R. H., Salmans, M., Gordon, W., Ho, H., & D, B. A. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.504399 · Cited by 60
Aging of hematopoietic stem cells: Intrinsic changes or micro-environmental effects?
Woolthuis, C. M., de Haan, G., & Huls, G. A. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.05.006 · Cited by 61
“In contrast, genes mediating myeloid specification and function were upregulated, strongly suggesting that the changes in lineage potential are underwritten by age-dependent changes in gene expression at the stem cell level [14].”
Kato, M., Yamashita, T., Suzuki, R., Matsumoto, K., Nishimori, H., Takahashi, S., Iwato, K., Nakaseko, C., Kondo, T., Imada, K., et al. (2016) · Leukemia · doi:10.1038/leu.2016.23 · Cited by 58
Wang, J., Morita, Y., Han, B., Niemann, S., Löffler, B., & Rudolph, K. L. (2016) · Nature Cell Biology · doi:10.1038/ncb3342 · Cited by 64
Khong, S. M. L., Lee, M. J., Kosaric, N., Khong, D., Dong, Y., Hopfner, Ú., Aitzetmüller, M. M., Duscher, D., Schäfer, R., & Gurtner, G. C. (2018) · Stem Cells · doi:10.1002/stem.2934 · Cited by 59
Acute Myeloid Leukemia: Aging and Epigenetics
Zjablovskaja, P., & Florian, M. C. (2019) · Cancers · doi:10.3390/cancers12010103 · Cited by 61
“Others (not discussed in the review) Increased expression of repetitive elements [63] Alternative protein isoforms [63] Altered expression of non-epigenetic cellular regulators [63,72]”
BackgroundClonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate
Wahlestedt, M., Erlandsson, E., Kristiansen, T., Lu, R., Brakebusch, C., Weissman, I. L., Yuan, J., Martin-Gonzalez, J., & Bryder, D. (2017) · Nature Communications · doi:10.1038/ncomms14533 · Cited by 59
Self-citationSu, T.-Y., Hauenstein, J., Somuncular, E., Dumral, Ö., Leonard, E., Gustafsson, C., Tzortzis, E., Forlani, A., Johansson, A., Qian, H., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52318-1 · Cited by 66
“Comprehensive epigenome studies have shown that gene loci associated with differentiation are hypermethylated, while loci correlated with HSC self-renewal are hypomethylated and display an increase in activating histone marks in aged HSCs 18,20 – 22 .”
InfluentialLoss of Slug Compromises DNA Damage Repair and Accelerates Stem Cell Aging in Mammary Epithelium
Gross, K. M., Zhou, W., Breindel, J. L., Ouyang, J., Jin, D. X., Sokol, E. S., Gupta, P. B., Huber, K., Zou, L., & Kuperwasser, C. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.06.043 · Cited by 58
Vennekens, A., Laporte, E., Hermans, F., Cox, B., Modave, E., Janiszewski, A., Nys, C., Kobayashi, H., Malengier‐Devlies, B., Chappell, J., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2100052118 · Cited by 59
“In other tissues, it was found that stem cells undergo an intrinsic aging process [such as in the hematopoietic system (15)] or regress in functionality because of the aging tissue milieu [as described in muscle and brain (16–18)].”
BackgroundChen, C., Mu, X., Zhou, Y. H., Ke, S., Geng, S., Liu, J., Wang, J., Chen, J., Li, T.-Y., & Wang, Y. (2013) · Acta Pharmacologica Sinica · doi:10.1038/aps.2013.136 · Cited by 58
Aged rats have an altered immune response and worse outcomes after traumatic brain injury
Sun, M., Brady, R. D., Casillas-Espinosa, P. M., Wright, D. K., Semple, B. D., Kim, H. A., Mychasiuk, R., Sobey, C. G., O'Brien, T. J., Vinh, A., et al. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.04.038 · Cited by 59
Locally sourced: site-specific immune barriers to metastasis
Correia, A. L. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00836-2 · Cited by 59
Adaptations of neutrophils in cancer
Ng, M. S. F., Cerezo‐Wallis, D., Ng, L. G., & Hidalgo, A. (2025) · Immunity · doi:10.1016/j.immuni.2024.12.009 · Cited by 60
Accumulation of DNA damage in the aged hematopoietic stem cell compartment
Beerman, I. (2016) · Seminars in Hematology · doi:10.1053/j.seminhematol.2016.11.001 · Cited by 55
“PII: S0037-1963(16)30118-4 DOI: http://dx.”
BackgroundInfluentialTranscriptional instability is not a universal attribute of aging
Warren, L. A., Rossi, D. J., Schiebinger, G. R., Weissman, I. L., Kim, S. K., & Quake, S. R. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00337.x · Cited by 56
“With respect to the HSCs, there is an order of magnitude expansion of the stem cell pool in mice between maturity and old age (Rossi et al., 2005; Rossi et al., 2007), implying that the average post-mitotic age of the cells we examined may be no more than a few months.”
BackgroundSelf-citationDNA Damage Response in Hematopoietic Stem Cell Ageing
Li, T., Zhou, Z., Ju, Z., & Wang, Z. (2016) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2016.04.002 · Cited by 56
“This finding correlates with the skewed hematopoietic lineage output in aged mice [8,36,42].”
BackgroundResultContribution of an Aged Microenvironment to Aging-Associated Myeloproliferative Disease
Vas, V., Wandhoff, C., Dörr, K., Niebel, A., & Geiger, H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031523 · Cited by 55
“Ineffective lymphoid cell production from aged HSCs has been for example described as a primarily cell-intrinsic aging-associated change [15].”
BackgroundRozhok, A. I., Salstrom, J. L., & DeGregori, J. V. (2014) · Aging · doi:10.18632/aging.100707 · Cited by 56
“The accumulation of somatic mutations and epigenetic changes has also been proposed to be a major cause of age-related stem cell decline, such as for hematopoietic stem cells (HSC) [5, 6].”
BackgroundMethodInfluentialFali, T., Fabre-Mersseman, V., Yamamoto, T., Bayard, C., Papagno, L., Fastenackels, S., Zoorab, R., Koup, R. A., Boddaert, J., Sauce, D., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.95319 · Cited by 59
Allo, V. C. M., Hauk, V. C., Sarbia, N., Pinto, N. A., Croci, D. O., Dalotto‐Moreno, T., Morales, R. M., Gatto, S. G., Cocco, M. N. M., Stupirski, J. C., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1922778117 · Cited by 55
“Studies of immune cell development revealed age-related changes on hematopoietic stem cells, leading to contraction of the lymphoid cell compartment and amplification of myeloid cell programs in both mouse and human (45, 46).”
BackgroundThe impact of aging on neutrophil functions and the contribution to periodontitis
Wang, Z., Saxena, A., Yan, W., Uriarte, S. M., de Siqueira, R. A. C., & Li, X. (2025) · International Journal of Oral Science · doi:10.1038/s41368-024-00332-w · Cited by 65
Aged Mice Are Unable To Mount an Effective Myeloid Response to Sepsis
Nacionales, D. C., Gentile, L. F., Vanzant, E. L., López, M. C., Cuenca, A. L., Cuenca, A. G., Ungaro, R. F., Li, Y. W., Baslanti, T. O., Bihorac, A., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1302109 · Cited by 54
Medhora, M. M., Gao, F., Gasperetti, T., Narayanan, J., Khan, A. H., Jacobs, E. R., & Fish, B. L. (2019) · Health Physics · doi:10.1097/hp.0000000000000920 · Cited by 55
Taking ageing into account in remyelination-based therapies for multiple sclerosis
Rist, J. M., & Franklin, R. J. M. (2008) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2008.04.027 · Cited by 55
“As with HSCs, gene expression studies have been undertaken to compare young and aged muscle satellite cells, which discovered differences in the transcriptional profiles as the cells age [32].”
InfluentialInflammation and Aging of Hematopoietic Stem Cells in Their Niche
Yang, D., & de Haan, G. (2021) · Cells · doi:10.3390/cells10081849 · Cited by 55
Mouse plasmacytoid dendritic cells derive exclusively from estrogen-resistant myeloid progenitors
Harman, B. C., Miller, J. P., Nikbakht, N., Gerstein, R. M., & Allman, D. (2006) · Blood · doi:10.1182/blood-2005-11-4545 · Cited by 57
Epigenetic regulation of hematopoietic stem cell fate
Meng, Y., & Nerlov, C. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2024.08.005 · Cited by 53
“Subtype-specific gene expression patterns have been investigated using surface markers, transgenic reporters [10], single HSC clone analysis [12], and in vivo barcoding [14, 28], and by comparing young and aged HSCs [16, 20, 29].”
B Cell Responses against Influenza Viruses: Short-Lived Humoral Immunity against a Life-Long Threat
Guthmiller, J. J., Utset, H. A., & Wilson, P. C. (2021) · Viruses · doi:10.3390/v13060965 · Cited by 56
“Moreover, hematopoiesis in elderly subjects is shifted towards the myeloid lineage, reducing the number of naïve B cells able to target drifted viral epitopes [141,142].”
BackgroundBrown, B. N., Haschak, M. J., Lopresti, S. T., & Stahl, E. C. (2017) · Seminars in Immunology · doi:10.1016/j.smim.2017.05.001 · Cited by 55
Krishnarajah, S., Ingelfinger, F., Friebel, E., Cansever, D., Amorim, A., Andreadou, M., Bamert, D., Litscher, G., Lutz, M., Mayoux, M., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00148-x · Cited by 57
Current Trends in Anti-Aging Strategies
Rosén, R., & Yarmush, M. L. (2023) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-120122-123054 · Cited by 56
Liu, Q., Li, J., Sun, X., Lin, J., Yu, Z., Xiao, Y., Li, D., Sun, B., Bao, H., & Liu, Y. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01735-w · Cited by 57
“Dlk1 + LT-HSCs demonstrate enhanced in vivo and vitro self-renewal, contradicting previous views of age-independent whole HSC self-renewal [151, 152, 155].”
Kucia, M., Masternak, M. M., Liu, R., Shin, D., Ratajczak, J., Mierzejewska, K., Spong, A., Kopchick, J. J., Bartke, A., & Ratajczak, M. Z. (2012) · AGE · doi:10.1007/s11357-011-9364-8 · Cited by 52
A systematic review on the role of environmental toxicants in stem cells aging
Hodjat, M., Rezvanfar, M. A., & Abdollahi, M. R. (2015) · Food and Chemical Toxicology · doi:10.1016/j.fct.2015.11.002 · Cited by 50
Madonna, R., Novo, G., & Balistreri, C. R. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.03.005 · Cited by 52
Aging, hematopoiesis, and the myelodysplastic syndromes
Chung, S. S., & Park, C. Y. (2017) · Blood Advances · doi:10.1182/bloodadvances.2017009852 · Cited by 53
“In addition, immunophenotypically defined hematopoietic stem cells (HSCs) are increased in number, presumably to compensate for a concomitant decline in their output on a per-cell basis to maintain blood production.(3,4) The characterization of HSC cellular and transcriptomal changes during aging has revealed alterati…”
BackgroundStem Cells Use Distinct Self-renewal Programs at Different AgesPreprint
Levi, B. P., & Morrison, S. J. (2008) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2008.73.049 · Cited by 54
“…in the rate at which stem cells divide, the fates they are likely to acquire, their frequency, and their self-renewal potential (Kuhn et al. 1996; Morrison et al. 1996; de Haan et al. 1997; de Haan and Van Zant 1999; Enwere et al. 2004; Rossi et al. 2005; Janzen et al. 2006; Molofsky et al. 2006).”
BackgroundAge-related changes in polycomb gene regulation disrupt lineage fidelity in intestinal stem cells
Tauc, H. M., Rodriguez‐Fernandez, I. A., Hackney, J. A., Pawlak, M., Oron, T. R., Korzelius, J., Moussa, H. F., Chaudhuri, S., Modrusan, Z. D., Edgar, B. A., et al. (2021) · eLife · doi:10.7554/elife.62250 · Cited by 53
Therapeutic Modulation of Autophagy in Leukaemia and Lymphoma
Djavaheri‐Mergny, M., Giuriato, S., Tschan, M. P., & Humbert, M. (2019) · Cells · doi:10.3390/cells8020103 · Cited by 52
Immune cell repertoires in breast cancer patients after adjuvant chemotherapy
Gustafson, C. E., Jadhav, R. R., Cao, W., Qi, Q., Pegram, M. D., Tian, L., Weyand, C. M., & Goronzy, J. J. (2020) · JCI Insight · doi:10.1172/jci.insight.134569 · Cited by 50
“The rules of naive B cell regeneration in chemotherapy-treated breast cancer patients is likely similar to early life, with the difference being that stem cells in middle-aged to older adults are less competent to differentiate into B cells (7, 8).”
BackgroundAguilar-Navarro, A. G., Meza-León, B., Gratzinger, D. A., Juárez-Aguilar, F. G., Chang, Q., Ornatsky, O., Tsui, H., Gómez, R. E., Hernández-Ramírez, A., Xie, S. Z.-J., et al. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2020.06.011 · Cited by 47
“, 2016), which has been linked to the influence of intrinsic (Beerman et al., 2010; Chambers et al., 2007; Rossi et al., 2005) and microenvironmental factors (Ergen et al.”
BackgroundMolecular Regulation of Cellular Quiescence: A Perspective from Adult Stem Cells and Its Niches
So, W., & Cheung, T. H. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7371-2_1 · Cited by 49
“For example, intrinsic functional and molecular changes in aged HSCs contribute to hematopoietic system aging [139].”
BackgroundDiscriminating cellular heterogeneity using microwell-based RNA cytometry
Dimov, I. K., Lu, R., Lee, E. P., Seita, J., Sahoo, D., Park, S.-M., Weissman, I. L., & Lee, L. P. (2014) · Nature Communications · doi:10.1038/ncomms4451 · Cited by 47
Self-citationBiechonski, S., Yassin, M., & Milyavsky, M. (2017) · Carcinogenesis · doi:10.1093/carcin/bgx002 · Cited by 54
“Decreased capacity to produce lymphoid cells is one of the best-documented manifestations of the functional changes observed in aged HSCs (128,129).”
BackgroundAging Schwann cells: mechanisms, implications, future directions
Painter, M. W. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.10.022 · Cited by 49
MAEA is an E3 ubiquitin ligase promoting autophagy and maintenance of haematopoietic stem cells
Wei, Q., Pinho, S., Dong, S., Pierce, H., Li, H., Nakahara, F., Xu, J., Xu, C., Boulais, P. E., Zhang, D., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22749-1 · Cited by 47
The impact of aging on primate hematopoiesis as interrogated by clonal tracking
Yu, K.-R., Espinoza, D. A., Wu, C., Truitt, L., Shin, T.-H., Chen, S., Fan, X., Yabe, I. M., Panch, S., Hong, S. G., et al. (2018) · Blood · doi:10.1182/blood-2017-08-802033 · Cited by 47
Poscablo, D. M., Worthington, A. K., Smith‐Berdan, S., & Forsberg, E. C. (2021) · Stem Cell Reports · doi:10.1016/j.stemcr.2021.04.016 · Cited by 47
“AgedHSCs seem tobe less effective at homing andengrafting in the host, suggesting that alterations to HSCs during aging persist (become intrinsic) on transplantation (Dykstra et al., 2011; Morrison et al., 1996; Rossi et al., 2005; Sudo et al., 2000).”
BackgroundResultInfluentialTeitell, M. A., & Mikkola, H. K. A. (2006) · Pediatric Research · doi:10.1203/01.pdr.0000205155.26315.c7 · Cited by 48
“Replicative stress on bone marrow HSCs from processes like serial transplantation or aging causes a gradual decline in self-renewal capacity (51,52).”
BackgroundEaton, S. M., Maue, A. C., Swain, S. L., & Haynes, L. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.7.4825 · Cited by 45
“In a subsequent study, they also showed that aged stem cells exhibit up-regulation of myeloid lineage genes and genes involved in leukemic transformation, which might account for reduced lymphocyte and enhanced production of myeloid lineage cells with aging (29).”
BackgroundChanging mutational and adaptive landscapes and the genesis of cancer
Liggett, L. A., & DeGregori, J. V. (2017) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2017.01.005 · Cited by 48
Considerations for successful cancer immunotherapy in aged hosts
Hurez, V. J., Padron, A. S., Svatek, R. S., & Curiel, T. J. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.10.002 · Cited by 46
“Hematopoietic stem cell generation of T cell precursors (Rossi et al., 2005) also declines.”
BackgroundImpact of aging on bone, marrow and their interactions
Hoffman, C. M., Han, J., & Calvi, L. M. (2018) · Bone · doi:10.1016/j.bone.2018.07.012 · Cited by 48
Fukushima, T., Tanaka, Y., Hamey, F., Chang, C., Oki, T., Asada, S., Hayashi, Y., Fujino, T., Yonezawa, T., Takeda, R., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.11.061 · Cited by 45
“The number of HSCs is increased after 1 year of mouse age (Beerman et al., 2010; Benz et al., 2012; Bernitz et al., 2016; Dykstra et al., 2011; Ema et al., 2000; Rossi et al., 2005; Yamamoto et al., 2018).”
Immune Memory in Aging: a Wide Perspective Covering Microbiota, Brain, Metabolism, and Epigenetics
Bulut, O. P., Kılıç, G., & Domínguez‐Andrés, J. (2021) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-021-08905-x · Cited by 50
“First of all, the differentiation capacity of long-term HSCs (LT-HSCs) reduces with advanced age [64].”
Backgroundde Jonge, H. J. M., de Bont, E. S. J. M., Valk, P. J. M., Schuringa, J. J., Kies, M. P., Woolthuis, C. M., Delwel, R., Veeger, N. J. G. M., Vellenga, E., Löwenberg, B., et al. (2009) · Blood · doi:10.1182/blood-2009-03-212688 · Cited by 46
Mechanisms involved in hematopoietic stem cell aging
Fujino, T., Asada, S., Goyama, S., & Kitamura, T. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04356-5 · Cited by 49
“Conversely, when young bone marrow cells were transplanted into irradiated aged recipient mice, they showed impaired repopulating potential and myeloid-skewed differentiation compared with those transplanted into young mice, suggesting a dependence of HSC functions on the bone marrow niche [17, 206].”
BackgroundIrradiation Alters Selection for Oncogenic Mutations in Hematopoietic Progenitors
Marusyk, A., Casás‐Selves, M., Henry, C. J., Zaberezhnyy, V., Klawitter, J., Christians, U., & DeGregori, J. V. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-0604 · Cited by 46
“(HSC), specified by c-KitSca1Lin CD34 Flk2 or CD150 CD48 Lin marker expression (22, 23), in the BM of mice irradiated 3 months prior at 5 Gy showed no significant differences relative to control mice (Supplementary Figs.”
BackgroundTransit-Amplifying Cell Frequency and Cell Cycle Kinetics Are Altered in Aged Epidermis
Charruyer, A., Barland, C. O., Yue, L., Wessendorf, H., Lü, Y., Lawrence, H. J., Mancianti, M., & Ghadially, R. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.127 · Cited by 45
“This is consistent with studies that showed a two- to sixfold decrease in cellular output from murine HSCs with age (Morrison et al., 1996; Rossi et al., 2005; Yilmaz et al., 2006).”
ResultImmunosenescence and multiple sclerosis: inflammaging for prognosis and therapeutic consideration
Thakolwiboon, S., Mills, E. A., Yang, J., Doty, J., Belkin, M., Cho, T., Schultz, C., & Mao‐Draayer, Y. (2023) · Frontiers in Aging · doi:10.3389/fragi.2023.1234572 · Cited by 48
Gu, B.-W., Fan, J., Bessler, M., & Mason, P. J. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00674.x · Cited by 45
“The number of BM cells, erythroid-committed progenitor cells, and c-Kit+, Sca-1+ and Lineage) (KLS) cells (Rossi et al., 2005), a BM cell fraction enriched in functional stem cells, was Stem cell aging in Dkc1 mutant mice, B.-W. Gu et al. ª 2011 The Authors Aging Cell ª 2011 Blackwell Publishing…”
BackgroundPellegrina, D. V. D. S., Severino, P., Barbeiro, H. V., Andreghetto, F. M., Velasco, I. T., de Souza, H. P., Machado, M. C. C., Reis, E. M. R., & da Silva, F. P. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128341 · Cited by 46
“Ageing of hematopoietic stem cells is associated with impaired hematopoiesis in the elderly [72, 73], which was attributed to a switch from canonical to non-canonical Wnt signaling [74].”
BackgroundPapathanasiou, P., Attema, J. L., Karsunky, H., Hosen, N., Sontani, Y., Hoyne, G. F., Tunningley, R., Smale, S. T., & Weissman, I. L. (2009) · Stem Cells · doi:10.1002/stem.232 · Cited by 49
Self-citationCytokine-Regulated GADD45G Induces Differentiation and Lineage Selection in Hematopoietic Stem Cells
Thalheimer, F. B., Wingert, S., Giacomo, P. D., Haetscher, N., Rehage, M., Brill, B., Theis, F. J., Hennighausen, L. G., Schroeder, T., & Rieger, M. A. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.05.010 · Cited by 44
“Moreover, GADD45G is upregulated in LT-HSCs of aged mice with reduced reconstitution ability (Rossi et al., 2005), and small hairpin RNA (shRNA)-mediated knockdown of GADD45G selected for aged HSCs with higher self-renewal potential (Wang et al.”
BackgroundImproved Cutaneous Healing in Diabetic Mice Exposed to Healthy Peripheral Circulation
Pietramaggiori, G., Scherer, S. S., Alperovich, M. A., Chen, B., Orgill, D. P., & Wagers, A. J. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.60 · Cited by 43
“Previous studies have shown an age-dependent deficit in the ability of transplanted hematopoietic stem cells from old mice to give rise to peripheral B-lymphocytes, coincident with an increased myelopoietic activity (Rossi et al., 2005).”
Self-citationImpact of stress on aged immune system compartments: Overview from fundamental to clinical data
Fali, T., Vallet, H., & Sauce, D. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.02.007 · Cited by 46
“Despite their self-renewal capability, the most reliable aging effect is the shift in balance from the lymphoid lineage observed in young adults to the myeloid linage found in the elderly (Rossi et al., 2005; Sudo et al., 2000; Sauce et al., 2011; Grover et al., 2016).”
BackgroundClonal hematopoiesis: Pre-cancer PLUS
Silver, A. J., & Jaiswal, S. (2019) · Advances in cancer research · doi:10.1016/bs.acr.2018.12.003 · Cited by 46
Gulati, G. S., Żukowska, M., Noh, J. J., Zhang, A., Wesche, D. J., Sinha, R., George, B. M., Weissman, I. L., & Szade, K. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1911024116 · Cited by 43
“These aged HSCs may arise from either the cell-intrinsic transition of balanced to myeloid-biased LT-HSCs or the clonal expansion of preexisting fractions of myeloid-biased LT-HSCs (13, 14, 16, 20, 21).”
BackgroundSelf-citationDudakov, J. A., Goldberg, G. L., Reiseger, J. J., Chidgey, A. P., & Boyd, R. L. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0802446 · Cited by 46
“There is also growing evidence that with age there is an intrinsic defect in hematopoietic stem cells and their ability to commit to the lymphoid lineage (8, 9).”
BackgroundDNA methylation analysis of murine hematopoietic side population cells during aging
Taiwo, O., Wilson, G. A., Emmett, W., Morris, T. J., Bonnet, D. A., Schuster, E. F., Adejumo, T., Beck, S., & Pearce, D. J. (2013) · Epigenetics · doi:10.4161/epi.26017 · Cited by 43
“DNA methylation patterns have been previously reported for young HSCs, and more recently DNA methylation patterns analyzed via bisulphite sequencing have been reported for aging HSCs.22-24 Here, we utilized Nano-MeDIP-seq for the analysis of the SP-HSC methylome and report global DNA methylation analysis of a cell pop…”
BackgroundInfluentialLee, J. S., Ward, W. O., Ren, H., Vallanat, B., Darlington, G. J., Han, E.-S., Laguna, J. C., DeFord, J. H., Papaconstantinou, J., Selman, C., et al. (2012) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2012.05.006 · Cited by 44
“ells from 22 to 23-month versus 2 to 3-month-old mice (Rossi et al., 2005) and brain”
BackgroundInfluentialInflammatory Changes in Bone Marrow Microenvironment Associated with Declining B Lymphopoiesis
Kennedy, D. E., & Knight, K. L. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601643 · Cited by 44
“With aging, B lineage progenitors decline, and HSCs are functionally more likely to differentiate to myeloid cells than to B lineage cells (10, 11).”
BackgroundNoda, S., Ichikawa, H., & Miyoshi, H. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.03.153 · Cited by 43
“old donors and engrafted mice with old donors [7,11].”
Metadata
- Authors
- Rossi, D. J., Bryder, D., Zahn, J. M., Ahlenius, H., Sonu, R., Wagers, A. J., & Weissman, I. L.
- Affiliations
- Joslin Diabetes Center (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-06-20
- Volume
- 102
- Issue
- 26
- Pages
- 9194-9199
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1153718
- OpenAlex
- W2131263031
- Cited by
- 1,152
- References
- 47
- Citations by year
- 2026: 44 · 2025: 56 · 2024: 49 · 2023: 55 · 2022: 56 · 2021: 80 · 2020: 57 · 2019: 71 · 2018: 57 · 2017: 59 · 2016: 67 · 2015: 54 · 2014: 56 · 2013: 63 · 2012: 55
- FWCI
- 24.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Damon Runyon Cancer Research Foundation
- National Institutes of Health
- Medical Research Council
- National Cancer Institute (R01CA086065)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Keywords
- hematopoietic stem cell aging, long-term hematopoietic stem cells, stem cell self-renewal, leukemic transformation, age-related immune decline, gene expression profiling
- MeSH terms
- Animals, Cell Separation, Cell Transformation, Neoplastic, Flow Cytometry, Gene Expression Regulation, Hematopoiesis, Hematopoietic Stem Cells, Leukemia, Mice, Inbred C57BL, Software, Stem Cells, Down-Regulation, Up-Regulation, Genome, Cellular Senescence, Cell Transplantation, Cell Lineage, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, 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.
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 ›
Are you an author, or do you see a problem with this page? Request a review
