The Axolotl Model for Regeneration and Aging Research: A Mini-Review

Although regeneration of tissues occurs in all adult tetrapods, the ability to regenerate complex structures such as limbs is limited to urodeles (newts and salamanders). Given that many of the biological processes and the signaling pathways that control these processes are highly conserved among all tetrapods, it is likely that humans have the potential to regenerate structures in the same way as salamanders. Thus the remarkable regenerative abilities of salamanders demonstrate what we reasonably can expect in terms of enhancing our regenerative potential. Although most of what is understood about regenerative mechanisms pertains to the repair of acute injuries, we assume that these same mechanisms could be utilized therapeutically to slow or even reverse chronic damage associated with aging. The axolotl model provides the opportunity to understand the behavior of cells to give the desired outcome of controlled growth and pattern formation leading to regeneration rather than aging and cancer. In this paper we present an overview of several important aspects of regeneration biology with an emphasis on the Mexican axolotl (Ambystoma mexicanum) as a model organism for identifying relevant signaling pathways and factors regulating limb regeneration. We also speculate about how these mechanisms could be utilized to reverse the aging process. By understanding the Received: November 2, 2010 Accepted: December 22, 2010 Published online: March 2, 2011 Dr. David M. Gardiner Department of Developmental and Cell Biology, Natural Sciences II Division University of California Irvine, 4111 Natural Sciences II Irvine, CA 92697-2305 (USA) Tel. +1 949 824 2792, E-Mail dmgardin @ uci.edu © 2011 S. Karger AG, Basel 0304–324X/11/0576–0565$38.00/0 Accessible online at: www.karger.com/ger McCusker/Gardiner Gerontology 2011;57:565–571 566 tinuous renewal process involving replacement of lost cells by adult stem cells, such as blood cells and the intestinal epithelium (see [1] ). This balance between loss and replacement is critical to maintaining tissue structure and function. The ability to replace cells within a specific tissue, though impressive, is limited and, with few exceptions (e.g. finger tips [2] ), we do not regenerate more complex structures that integrate the structure and function of multiple tissues. In contrast, one group of tetrapods, the urodele amphibians (newts and salamanders) do have the ability to regenerate complex structures such as limbs and spinal cords. The remarkable regenerative abilities of salamanders demonstrate what we reasonably can expect in terms of enhancing our regenerative potential. While the ability of these animals to regenerate entire organs seems extraordinary, the mechanisms of regeneration involve many basic biological processes regulated by conserved signaling pathways [3] . Thus, we can expect to stimulate regeneration in a human by the same mechanisms used by the axolotl. In this review, we present an overview of the Mexican axolotl (Ambystoma me xicanum) as a model organism for identifying the relevant signaling pathways and factors regulating limb regeneration, and speculate about how to enhance our regenerative responses to both acute injury and the accumulation of chronic damage to slow or even reverse the loss of both tissue and organ function associated with aging. Mechanisms of Regeneration in Response to Acute