Advancements to the Axolotl Model for Regeneration and Aging

Abstract

Loss of regenerative capacity is a normal part of aging. However, some organisms, such as the Mexican axolotl, retain striking regenerative capacity throughout their lives. Moreover, the development of age-related diseases is rare in this organism. In this review, we will explore how axolotls are used as a model system to study regenerative processes, the exciting new technological advancements now available for this model, and how we can apply the lessons we learn from studying regeneration in the axolotl to understand, and potentially treat, age-related decline in humans.

Keywords: Aging; Axolotl; Cancer; Immune system; Nerve signaling; Regeneration; Scar formation; Technological advances.

Figure 1:. Axolotl continue to grow after sexual maturity.

Live images of a hatchling axolotl (~3 weeks old), young juvenile (~3 months old), late juvenile (~5 months old), sexually mature adult (~1 year old), and a 3-year-old adult show the dramatic increase in size over time.

Figure 2:. Changes in skin morphology in axolotl as they age.

A) Live images of the forelimbs of a young juvenile (top) and a sexually mature adult (bottom) staged animals. B) Histology staining of sections of the limbs in A showing the full thickness skin where “1” indicates the dermal layer from the juvenile staged limb, and “2” indicates the dermal layer on the adult staged limb.

Figure 3:. The Accessory Limb Model (ALM) is an assay to study limb regeneration.

A live image of an ectopic limb that has formed from making a wound site with a nerve on the anterior side of the limb on the RFP+ host animal (red) that was grafted with a blastema from a GFP+ donor animal (green).

Figure 4:. Decline of regenerative capacity in limbs repeatedly amputated at the same location.

Example whole-mount skeletal preparations of the resulting regenerates form from limbs that have been amputated in the same location 1, 2, 3, 4, or 5 times. Bryant et al. observed a marked decrease in regenerative potential with increasing number of amputations (republished with permission from [23]).