Cdc42 and aging of hematopoietic stem cells : Current Opinion in Hematology (original) (raw)

HEMATOPOIESIS: Edited by Hal E. Broxmeyer

aDepartment of Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany

bDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio, USA

Correspondence to Hartmut Geiger, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Tel: +1 513 636 1338; fax: +1 513 636 3768; e-mail: [email protected]

Abstract

Purpose of review

Hematopoietic stem cells (HSCs) continuously provide mature blood cells during the lifespan of a mammal. The functional decline in hematopoiesis in the elderly, which involves a progressive reduction in the immune response and an increased incidence of myeloid malignancy, is partly linked to HSC aging. Molecular mechanisms of HSC aging remain unclear, hindering rational approaches to slow or reverse the decline of HSC function with age. Identifying conditions under which aged HSCs become equivalent to young stem cells might result in treatments for age-associated imbalances in lymphopoiesis and myelopoiesis and in blood regeneration.

Recent findings

Aging of HSCs has been for a long time thought to be an irreversible process imprinted in stem cells due to the intrinsic nature of HSC aging. Mouse model studies have found that aging is associated with elevated activity of the Rho GTPase Cdc42 in HSCs that is causative for loss of polarity, altered epigenetic modifications and functional deficits of aged HSCs. The work suggests that inhibition of Cdc42 activity in aged HSCs may reverse a number of phenotypes associated with HSC aging.

Summary

Maintaining the regenerative capacity of organs or organ systems may be a useful way to ensure healthy aging. A defined set of features phenotypically separate young from aged HSCs. Aging of HSCs has been thought to be irreversible. Recent findings support the hypothesis that functional decline of aged HSCs may be reversible by pharmacological intervention of age altered signaling pathways and epigenetic modifications.