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

  1. Robert A.J. Signer1,
  2. Encarnacion Montecino-Rodriguez1,
  3. Owen N. Witte2,3,4, and
  4. Kenneth Dorshkind1,5
  1. 1 Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA;
  2. 2 Department of Microbiology, Immunology, and Molecular Genetics, University of California at Los Angeles, Los Angeles, California 90095, USA;
  3. 3 Department of Molecular and Medical Pharmacology, University of California at Los Angeles, Los Angeles, California 90095, USA
  4. 4 The Howard Hughes Medical Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA

Abstract

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.

Keywords

Footnotes

| Table of Contents

This Article

  1. doi: 10.1101/gad.1715808 Genes & Dev. 22: 3115-3120 Copyright © 2008, Cold Spring Harbor Laboratory Press

Article Category

Share

Current Issue

  1. March 1, 2024, 38 (5-6)
  1. Current Issue
  1. Alert me to new issues of G&D

Life Science Alliance