Embryonic Stem Cells Do Not Age After Oxidative Stress
By Guo et al. Stem Cell Dev., January 21, 2010
The molecular basis of aging is still not completely
understood. One of the critical findings in this area has been that with each
cellular division the ends of the chromosomes, called telomeres, become
shorter. After approximately 50 cell divisions the telomeres of cells are so
short that the cells undergo a process called senescence, which is a type of
cellular aging. There are certain exceptions to this. For example memory T and
B cells, stem cells, and cancer cells have the ability to divide for large
number of times, if not indefinitely. They are able to escape the process of
telomere shortening and associated senescence by expressing an enzyme called
telomerase, which repairs the telomeres after each cell doubling. The
importance of telomerase in allowing cellular immortality is seen in experiments
in which cells that do not express telomerase are genetically engineered to
express it, which results in cellular ability to proliferate indefinitely.
In addition to cell replication, one of the most potent
causes of telomere shortening is oxidative stress. Studies in this area have
been reviewed in a paper by Erusalimsky et al. Mechanisms of Endothelial
Senescence Exp Physiol. 2009 Mar;94(3):299-304, which essentially point to
several protein alterations induced by oxidative stress that either inhibit
ability of telomerase, or cause cleavage of telomeres.
While the effect of oxidative stress are well known on
differentiated cells, little is known regarding how undifferentiated cells, like
stem cells, respond to oxidative stress in terms of accelerated aging. In a
recent study Guo et al. Effects of Oxidative Stress on Mouse Embryonic Stem
Cell Proliferation, Apoptosis, Senescence, and Self-Renewal. Stem Cells Dev.
2010 Jan 21, the investigators addressed this question. Treatment of cells
with hydrogen peroxide was shown to induce cellular suicide at high
concentrations in both differentiated cells and mouse embryonic stem cells. In
contrast, concentrations of hydrogen peroxide that are capable to induce
accelerated aging (senescence) in differentiated cells did not affect embryonic
stem cells. Exposure to oxidative stress induced the stem cells to stop
proliferating, which was believed to allow a re-organization of gene expression
so as to not undergo cellular senescence.
These data suggest that embryonic stem cells have certain
cellular components that are not only capable of sensing oxidative stress, but
also responding through protection of replicative activity. Since senescence of
the stem cell compartment would theoretically have disastrous consequences, it
will be interesting to see if similar mechanisms are present in adult stem cells
such as bone marrow, cardiac specific, and hepatic stem cells.