Stem Cell Aging
Much of age-related morbidity in mammals may be determined by the influence of aging on stem cell function. We have found that stem cells from the hematopoietic and nervous systems undergo strikingly conserved changes in their properties as they age, including declining self-renewal capacity.
We have identified a network of heterochronic gene products that regulates stem cell maintenance throughout life while also regulating the temporal changes in stem cell properties required to match the changing growth and regeneration demands of fetal and adult tissues. Proto-oncogenic signals dominate during fetal development when tissue growth is rapid but cancer risk is low, and tumor-suppressor mechanisms are amplified during aging when there is little tissue growth but cancer risk is high. The increase in tumor suppressor expression during aging delays the development of cancer but also impairs stem cell function and tissue regenerative capacity.