Revisiting the relationship between regenerative ability and aging

Abstract

Contrary to the longstanding view that newts (Notophthalamus viridescens), but not axolotls (Ambystoma mexicanum), can regenerate a lens, a recent report in BMC Biology by Panagiotis Tsonis and colleagues shows axolotls indeed possess this ability during early larval stages. In contrast, they show that zebrafish never posses this ability, even as embryos. This underscores the importance of comparing regenerative ability across species and reinforces the need to consider organ regeneration in the context of evolution, development, and aging.

Figure 1

Reparative regeneration as a function of developmental stage among vertebrate models of regeneration. Panels depict how the regenerative ability of homologous structures varies across ontogeny for the primary vertebrate models of regeneration. Regenerative ability is presented on a 0 to 5 scale; five represents perfect regeneration and zero no regeneration. Major ontogenetic stages are represented as embryo, larva, juvenile and adult with metamorphosis, puberty or both indicated for each species. (a) Zebrafish exhibit lifelong regenerative capacity of spinal cord, brain, and heart. They cannot regenerate a lens at any time in development and while pectoral fins (homologous to tetrapod limbs) regenerate in juveniles, their regenerative capacity is reduced following puberty, with females retaining a higher capacity for complete regeneration. (b) Salamanders and newts are the archetypical tetrapod regenerator, retaining near perfect regeneration of most organs and appendages well into adulthood (although almost no studies have tested these abilities in old animals). They do, however, experience a decline in limb regeneration following metamorphosis, which usually manifests as patterning defects and loss of limb elements. Axolotls can only regenerate lenses as early stage larvae. (c) Although most frogs exhibit some degree of regeneration as larvae, with the exception of limited digit and very restricted limb regeneration in some species, they do not exhibit regenerative ability as adults. (d) Mammals exhibit some regenerative capacity as embryos but lose almost all of this ability before or shortly after birth for the structures listed.