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Bcl-2-interacting killer (Apoptosis inducer NBK) (BIP1) (BP4) [NBK]


Age-related transcription levels of KU70, MGST1 and BIK in CD34 hematopoietic stem and progenitor cells.

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.

MeSH Terms

  • Adult
  • Adult Stem Cells
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging
  • Antigens, CD34
  • Antigens, Nuclear
  • Apoptosis Regulatory Proteins
  • Cellular Senescence
  • Cluster Analysis
  • DNA-Binding Proteins
  • Fetal Blood
  • Gene Expression Profiling
  • Glutathione Transferase
  • Hematopoietic Stem Cells
  • Humans
  • Infant, Newborn
  • Ku Autoantigen
  • Membrane Proteins
  • Middle Aged
  • Mitochondrial Proteins
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • RNA, Messenger
  • Reproducibility of Results
  • Transcription, Genetic