Age-related transcription levels of KU70, MGST1 and BIK in CD34+ hematopoietic stem and progenitor cells.
Mech Ageing Dev
; 128(9): 503-10, 2007 Sep.
Article
em En
| MEDLINE
| ID: mdl-17714764
ABSTRACT
Despite the known longevity of human hematopoietic stem and progenitor cells (HSC), numerous functional impairments of these cells can be observed in an age-dependent manner. However, the molecular alterations associated with aging of HSC are largely unknown. Therefore, we scrutinized gene expression patterns of HSC from newborn, young and old healthy donors. CD34+ HSC were isolated via immuno-magnetic separation and evaluated by FACS analysis. We performed cDNA macroarray analyses on a first set of CD34+ samples (n=13). We found the genes encoding KU-antigen 70 kD (KU70), microsomal glutathione S-transferase 1 (MGST1) and BCL2-interacting killer (BIK) to possess age-related mRNA expression levels. KU70 is a DNA repair gene and part of the DNA-dependent protein kinase (DNA-PK) complex. Its expression was negatively correlated with donor age showing highest expression levels in newborn, 2.6-fold lower levels in young and 6.3-fold lower levels in old donors. The transcription levels of MGST1, a gene protecting against oxidative stress, progressively increased with age. Expression was lowest in newborn, 2.6-fold higher in young and 4.3-fold higher in old donors. BIK is a proapoptotic gene and its expression was positively correlated with donor age lowest in newborn, 1.8-fold higher in young and 4.1-fold higher in old donors. These findings were confirmed with an independent, second set of CD34+ samples (n=16) by means of quantitative real-time RT-PCR. Elucidation of age-dependent molecular alterations in healthy HSC facilitate a better understanding of functional impairments in hematopoiesis and may become valuable for anti-aging drug development and the emerging field of regenerative medicine.
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Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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Envelhecimento
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Células-Tronco Hematopoéticas
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Antígenos CD34
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Antígenos Nucleares
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Proteínas de Ligação a DNA
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Proteínas Reguladoras de Apoptose
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Células-Tronco Adultas
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Glutationa Transferase
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Proteínas de Membrana
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article