Aging and cancer resistance in lymphoid progenitors are linked processes conferred by p16 Ink4a and Arf
Open accessAbstract
Lymphoid progenitors exhibit severe growth defects during aging while myelopoiesis is relatively unperturbed. These effects are due in part to the preferential expression of p16 Ink4a and Arf in aged lymphoid progenitors. Their increased expression contributes to reduced growth and survival of lymphoid progenitors and makes them refractory to malignant transformation. Down-regulation of p16 Ink4a and Arf in aged lymphoid progenitors reverted the senescent phenotype and restored susceptibility to transformation. These data provide a molecular explanation for the preferential effects of aging on lymphopoiesis, suggest that inhibiting p16 Ink4a and Arf expression can rejuvenate B lymphopoiesis, and link aging and cancer resistance.
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Both Ink4a and Arf expression increase in pro-B cells from old mice, and inhibiting their expression can partially reverse aging effects.
“recent studies have shown that both Ink4a and Arf expression increases in pro-B cells from old mice and that inhibiting their expression can partially reverse the effects of aging (81).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [81]
The Ink4a/GFP shRNA used was previously validated.
“We therefore used a loss-of-function approach in which ETPs isolated from old mice were transduced with a previously validated Ink4a/GFP shRNA 26 or GFP-only-containing retroviral vectors”
From Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a (2012) · cites this paper as [26]
Loss of Bmi-1 is correlated with increased Ink4a expression in pro-B cells from old mice.
“Whereas loss of Bmi-1 was shown to be correlated with increased expression of Ink4a in pro-B cells from old mice, 26 its levels remained constant in old ETPs.”
From Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a (2012) · cites this paper as [26]
Bmi-1 expression is decreased in pro-B cells from old mice.
“We previously demonstrated decreased expression of Bmi-1 and increased levels of Ink4a in pro-B cells from old mice.26”
From Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a (2012) · cites this paper as [26]
The regulation of Ink4a expression in aging B-cell and T-cell progenitors differs.
“The regulation of Ink4a expression in aging B-and T-cell progenitors also appears to differ.”
From Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a (2012) · cites this paper as [26]
Ink4a expression is increased in pro-B cells from old mice.
“We previously demonstrated decreased expression of Bmi-1 and increased levels of Ink4a in pro-B cells from old mice.26”
From Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a (2012) · cites this paper as [26]
Early T-lymphoid progenitors are exquisitely dependent on CDK4/6 activity.
“early T-lymphoid progenitors are exquisitely dependent on CDK4/6 activity”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [43]
Early T-lymphoid progenitors are very sensitive to p16 upregulation for induction of senescence during aging.
“are very sensitive to p16 upregulation for induction of senescence during aging.42,43”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [43]
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References 40 · Cited by 102
Research works printed but not linked: 1
- Williams, R.T., Roussel, M.F., and Sherr, C.J. 2006. Arf gene loss en- hances oncogenicity and limits imatinib response in mouse models of Bcr-Abl-induced acute lymphoblastic leukemia. Proc. Natl. Acad. Sci. 103: 6688-6693.
- Authors
- Signer, R. A. J., Montecino-Rodriguez, E., Witte, O. N., & Dorshkind, K.
- Affiliations
- University of California, Los Angeles (US)
- Howard Hughes Medical Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2008-11-15
- Volume
- 22
- Issue
- 22
- Pages
- 3115-3120
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2593609
- OpenAlex
- W2035173277
- Cited by
- 102
- References
- 40
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 5 · 2014: 7 · 2013: 8 · 2012: 10
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- California Institute for Regenerative Medicine
- National Institutes of Health (AI28697, CA16042)
- National Institute on Aging (AG-21450, R01AG021450)
- National Cancer Institute (CA-16 042, P30CA016042)
- National Institute of Allergy and Infectious Diseases (AI-28 697, P30AI028697)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- aging, lymphoid progenitors, p16INK4a, ARF, cellular senescence, lymphocyte development, B cell development, tumor resistance, malignant transformation, myelopoiesis
- MeSH terms
- Aging, Animals, B-Lymphocytes, Cell Transformation, Neoplastic, Cells, Cultured, Flow Cytometry, Hematopoietic Stem Cells, Mice, Inbred C57BL, Transfection, Gene Expression, Cyclin-Dependent Kinase Inhibitor p16, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Protein p14ARF, Green Fluorescent Proteins, Mice
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