Aging and cancer resistance in lymphoid progenitors are linked processes conferred by p16Ink4a and Arf

RAJ Signer, E Montecino-Rodriguez… - Genes & …, 2008 - genesdev.cshlp.org
RAJ Signer, E Montecino-Rodriguez, ON Witte, K Dorshkind
Genes & development, 2008genesdev.cshlp.org
Lymphoid progenitors exhibit severe growth defects during aging while myelopoiesis is
relatively unperturbed. These effects are due in part to the preferential expression of
p16Ink4a 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 p16Ink4a and Arf in aged lymphoid
progenitors reverted the senescent phenotype and restored susceptibility to transformation …
Lymphoid progenitors exhibit severe growth defects during aging while myelopoiesis is relatively unperturbed. These effects are due in part to the preferential expression of p16Ink4a 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 p16Ink4a 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 p16Ink4a and Arf expression can rejuvenate B lymphopoiesis, and link aging and cancer resistance.
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