Aging of signal transducton in stem cells

M.E. Carlson, M.J. Conboy, M. O'Connor, H. Silva, M. Hsu and I. M. Conboy
Bioengineering, University of Berkeley, CA

While the underlying reasons and molecular mechanisms of physiological aging are not identical in various adult organ systems, one common characteristic is insufficient or failed regenerative processes. This age-specific lack of tissue repair, which leads to degeneration and loss of function, is perfectly exemplified in skeletal muscle and we are attempting to understand this aging process in cellular and molecular terms.

Importantly, we have identified the key biochemical pathways that function well in young muscle stem cells residing in their own young niches, and which allow efficient tissue maintenance and repair. These same pathways become deregulated with age, causing poor regeneration of old skeletal muscle. Forced manipulation of these signaling networks controls muscle stem cell responses and rejuvenates the capacity for tissue regeneration. Importantly, the tissue produced by the "aged" stem cells appears to be relatively young with respect to telomerase activity and telomere length. These findings suggest novel strategies for improving regenerative responses of endogenous stem cells endogenous in old organs, and for combating the age-specific loss of functional tissue.

Keywords: Muscle stem cell, Niche aging, Signal transduction