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

被引：82

作者：

Signer, Robert A. J. ^{[1
]}

Montecino-Rodriguez, Encarnacion ^{[1
]}

Witte, Owen N. ^{[2
,3
,4
]}

Dorshkind, Kenneth ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90095 USA

来源：

GENES & DEVELOPMENT | 2008年 / 22卷 / 22期

关键词：

Aging; hematopoiesisl; cancer; p16(Ink4a); Arf; Bmi-1;

D O I：

10.1101/gad.1715808

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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. Downregulation 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.

引用

页码：3115 / 3120

页数：6

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