Document Detail


Cdc42 and aging of hematopoietic stem cells.
MedLine Citation:
PMID:  23615056     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Hartmut Geiger; Yi Zheng
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current opinion in hematology     Volume:  20     ISSN:  1531-7048     ISO Abbreviation:  Curr. Opin. Hematol.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-06     Completed Date:  2013-10-23     Revised Date:  2014-06-17    
Medline Journal Info:
Nlm Unique ID:  9430802     Medline TA:  Curr Opin Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  295-300     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aging / physiology*
Animals
Cell Aging / physiology
Hematopoiesis / physiology*
Hematopoietic Stem Cells / physiology*
Humans
Mice
Models, Animal
Signal Transduction / physiology
cdc42 GTP-Binding Protein / metabolism*
Grant Support
ID/Acronym/Agency:
AG040118/AG/NIA NIH HHS; DK077762/DK/NIDDK NIH HHS; HL076604/HL/NHLBI NIH HHS; R01 AG040118/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
EC 3.6.5.2/cdc42 GTP-Binding Protein
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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