Seminar in Biological Mechanisms of Aging and Cancer/Stem cell exhaustion

“The Hallmarks of Aging” review, published in 2013, identifies stem cell exhaustion as one of the nine hallmarks that contribute to aging. Stem cells are undifferentiated cells that have the potential to produce indefinitely more cells of the same type or other cell types through differentiation. Stem cell exhaustion is when tissues lose their ability to regenerate. As organisms age, the number of stem cells they have decreases. Losing this regenerative potential means losing the ability to replace damaged cells, which leads to many aging symptoms.[1]

Graphical abstract illustrating findings highlighted in "The ageing systemic milieu negatively regulates neurogenesis and cognitive function" by Villeda et. al.[2]

As a leading cause of aging at the tissue and organismal levels, past and ongoing research attempts to identify the many causes and consequences of stem cell exhaustion. An example of this research is an article published in 2011 by Villeda et. al called “The ageing systemic milieu negatively regulates neurogenesis and cognitive function.” This study used mice to investigate if factors outside of the brain caused a decline in neural stem cells and neurogenesis, or the growth and development of new neurons. By putting blood from old mice into young mice, they identified factors in the blood as contributors to the decline in neurogenesis and cognitive function due to aging. In particular, CCL11, a substance secreted by certain cells of the immune system that is involved in allergic responses, was found to increase with age and contribute to the age-related decline in neurogenesis and cognitive function. They also found that neurogenesis could be rescued by neutralizing CCL11 with an anti-CCL11 antibody. Overall, factors in the blood change with age and lead to a decline in new neuron production.[2]

  1. López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The Hallmarks of Aging. Cell, 153(6), 1194-1217. doi:10.1016/j.cell.2013.05.039
  2. 2.0 2.1 Villeda, S. A., Luo, J., Mosher, K. I., Zou, B., Britschgi, M., Bieri, G., . . . Wyss-Coray, T. (2011). The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature, 477(7362), 90-94. doi:10.1038/nature10357