Aging and cancer resistance in lymphoid progenitors are linked processes conferred by p16Ink4a and Arf.
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.
Signer
Robert A J
RA
Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA.
Montecino-Rodriguez
Encarnacion
E
Witte
Owen N
ON
Dorshkind
Kenneth
K
D000375:Aging; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics* / Q000378:metabolism
D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF; D049452:Green Fluorescent Proteins