X-linked genetic factors regulate hematopoietic stem-cell kinetics in females

X inactivation makes females mosaics for 2 cell populations, usually with an approximate 1:1 distribution. Skewing of this distribution in peripheral blood cells is more common among elderly women.(1-3) The depletion of hematopoietic stem cells followed by random differentiation may explain the acquired skewing with age.(4) However, an animal model suggests that selection processes based on X-linked genetic factors are involved.(5) We studied peripheral blood cells from 71 monozygotic twin pairs aged 73 to 93 years and from 33 centenarians, and we found that with age, 1 of the cell populations becomes predominant for most women. We also observed a strong tendency for the same cell line to become predominant in 2 co-twins. This suggests that X-linked genetic factors influence human hematopoietic stem cell kinetics. The fact that females have 2 cell lines with different potentials could be one of the reasons women live longer than men, (Blood, 2000;95:2449-2451) (C) 2000 by The American Society ct Hematology.