Stem Cells Age as Well

Today I thought I'd point out an interesting post from the Buck Institute team on the topic of stem cell aging. The good news here is that the characteristic age-related decline of stem cell function is an issue that the research community has to engage with on the way to developing effective treatments based on their work. It is unavoidable: the majority of regenerative medicine based on the use of stem cells is most applicable to age-related diseases, yet the old and damaged tissue environment disrupts stem cell activity.

What happens to adult stem cells as a person ages? Can they always maintain their regenerative capacity? The answer is no. Adult stem cells maintain tissue homeostasis and differentiate into the cell types that make up the tissue in which they reside, however these processes become less efficient over time. Adult stem cell dysfunction caused by aging has been reported in many organ systems including the heart, muscle, and bone marrow. Some adult stem cell populations like neural stem cells in the brain and melanocyte stem cells in hair follicles actually decline with age. Both adult stem cell dysfunction and a decline in number translate to a reduced regenerative response to tissue or age-related damage.

A few of the culprits: DNA damage occurs in aging stem cells over time because of factors present inside and outside of the cells and because of exposure to genotoxic stress (chemical factors that cause genetic mutations). The machinery that repairs DNA in older stem cells does not function as precisely, and this can cause genomic instability, cell death, or even cancer if a person is really unlucky. Cellular senescence is a term that refers to cells that have entered a state where they can no longer proliferate and divide. Senescence occurs in older stem cells because of elevated cellular stress. Senescent stem cells are bad news because they secrete factors that can cause inflammation and stem cell dysfunction, which further exacerbates symptoms of aging and disease. Then there is mitochondrial dysfunction. Mitochondria are the batteries that power our cells. Mitochondria have their own genome, and in aging stem cells, mitochondrial DNA can be damaged, which impairs mitochondrial function and consequently, adult stem cell function.

So how do we solve the problem of aging stem cells? One obvious approach is to rejuvenate adult stem cells by preventing DNA damage, cellular senescence, and mitochondrial dysfunction. Another strategy is to transplant healthy adult stem cells from a donor into a patient with disease or damaged tissue. However, the issue with adult stem cell transplantation is that the environment (called the niche) into which you transplant healthy stem cells may contain toxic factors (caused by disease or damage) that will kill off the newly transplanted stem cells or impair their function. Thus, a better approach would be to fix or reverse aging phenotypes in the surviving stem cells and other mature cells in that niche, and then transplant healthy donor stem cells into a rejuvenated, healthy environment.

One last thing to consider as one addresses the aging adult stem cell issue is when to intervene therapeutically. Trying to restore adult stem cell function in already diseased or older tissue might not be as effective as preventing damage from accumulating in the same stem cells earlier in life. Prevention of stem cell aging would be a promising strategy to fight aging itself, but that would require the ability to predict or diagnose disease onset in healthy people, which is a huge and complicated endeavor.