Reactiving Dormant Stem Cells in the Aging Heart
Stem cell populations decline in activity and possibly size with aging. This is most likely an evolved response to rising levels of damage that works to reduce cancer risk but causes increasing frailty and degeneration of tissue function. The exact mechanisms are probably different in different cell types and organs, but researchers have been making some progress in uncovering ways to trigger various types of stem cells to return to work. This can produce considerable benefits in terms of improved regeneration and tissue maintenance, but is probably going to come with an associated raised risk of cancer. For best effect we want researchers to work on removing the underlying damage that causes stem cells to go silent, rather than try to boost the activity of a damaged engine.
Here is an example of recent research of this type, in which a way to revive some of the heart's stem cells is found, and the proximate cause of their quiescence identified:
Hypoxia favors stem cell quiescence, while normoxia is required for their activation; but whether cardiac stem cell (CSC) function is regulated by the hypoxic/normoxic state of the cell is currently unknown. A balance between hypoxic and normoxic CSCs may be present in the young heart, although this homeostatic control may be disrupted with aging. Defects in tissue oxygenation occur in the old myocardium, and this phenomenon may expand the pool of hypoxic CSCs, which are no longer involved in myocyte renewal.Here we show that the senescent heart is characterized by an increased number of quiescent CSCs with intact telomeres that cannot reenter the cell cycle and form a differentiated progeny. Conversely, myocyte replacement is controlled only by frequently dividing CSCs with shortened telomeres; these CSCs generate a myocyte population that is chronologically young but phenotypically old. Telomere dysfunction dictates their actual age and mechanical behavior. However, the residual subset of quiescent young CSCs can be stimulated in situ by stem cell factor reversing the aging myopathy.
Our findings support the notion that strategies targeting CSC activation and growth interfere with the manifestations of myocardial aging in an animal model. Although caution has to be exercised in the translation of animal studies to human beings, our data strongly suggests that a pool of functionally-competent CSCs persists in the senescent heart and this stem cell compartment can promote myocyte regeneration effectively, correcting partly the aging myopathy.