Mechanisms underlying stem cell depletion in ageing.
Abstract
As we age, our bodies lose the ability to repair damaged tissues. This impairment may be due to age-related deficits in our regenerative stem cells. Stem cells reside in specialized areas called stem cell niches. Ageing may cause alterations in the stem cells directly or may alter the stem cell niche to generate deficits. However, systematic studies mapping stem cell deficits and alterations to stem cell niche are lacking. Here, I investigated the bone marrows of young and aged mice to determine age-related changes in the microenvironment that may alter resident stem cells.
To achieve my research objective, I examined the bone tissues of male and female C57BL/6N mice at different ages, ranging from 8 to 71 weeks of age. This corresponds to 20-75 human years. I performed bone marrow morphometric analyses and show an increase in marrow adiposity with advanced ageing in both male and female mice. I then stained bone tissues and noted increased immunoreactivity to stem cell antigen (SCA1) only at the middle age in female mice. This increase was not seen in male mice. Screening for various genes in the marrow flush samples indicated a possible role of growth and sex steroid hormone receptors in mediating some of the changes. However, empirical evidence will be needed to determine the causative agent in increased bone marrow adiposity.
My studies may allow for a better understanding of how ageing affects the composition and function of marrow resident stem cell populations.