A basic signaling
pathway known to play important roles in normal cell and cancer cell formation
also plays an unexpected role as a molecular switch that controls the aging
process of hematopoietic stem cells (HSCs), according to research led by Cincinnati
Children’s and the University of Ulm in Germany.
scientists hope their findings will lead to ways for the elderly to boost their
immune systems, fight illnesses and enhance overall vitality.
is a large amount of data showing that blood stem cell function declines during
aging, the molecular processes that cause this remain largely unknown. This
prevents rational approaches to attenuate stem cell aging,” says Hartmut Geiger, PhD, senior
investigator and a scientist at Cincinnati Children’s and the University of
Ulm. “This study puts us significantly closer to that goal.”
functioning HSCs – which form in the bone marrow – produce the various types of
blood cells necessary to a healthy immune system. HSCs also are important for regenerating
other important cells in the body.
In mouse models,
the team observed that as HSCs age, a normal pattern in the Wnt signaling
pathway within HSCs shifts into an
atypical pattern that leads to cell death.
appears to be triggered by sharply increased expression of the protein Wnt5a. In
mice bred to be unable to express Wnt5a, the aging process of their HSCs was
delayed compared to normal mice, the new study shows, while suppression of
Wnt5a in aged HSCs rejuvenated them.
were published online Oct. 20, 2013, in Nature.
While the study advances
our understanding of how aging works at the molecular level, much more research
is needed to make these findings therapeutically relevant, Geiger says. It remains unclear whether a drug can be
developed to block Wnt5a in humans without causing other harm.
by Nick Miller, Cincinnati Children’s. Contact: