Why we mammals can’t regenerate entire body parts like other animals (and why this limitation might not be as definitive)

There are aspects of our biology that we assume to be inevitable. For example, if we lose an arm or a leg, they will not grow back.

The second study approaches regeneration from a different perspective, but reaches a complementary conclusion. Since frog tadpoles live in environments with lower oxygen availability than terrestrial mammals, the researchers analyzed the role of this factor in regeneration.

By comparing the developing limbs of both species, they found that oxygen levels act as a true biological switch. Under low oxygen conditions (hypoxia), the HIF1A factor is activated, which promotes cell proliferation and migration and facilitates the expression of genes associated with regeneration.

On the contrary, under normal oxygen conditions, characteristic of mammals, these processes are blocked. In addition, oxygen also influences DNA structure through epigenetic changes that determine whether regenerative genes are active or silenced.

In this experimental context, based on embryonic limbs in vitro, the authors show that it is possible to activate early responses associated with regeneration in mammalian tissues, rather than induce complete regeneration.

Both works point in the same direction: mammals may not completely lack regenerative programs. Rather, these would not be activated in the usual conditions in which they live, a biological environment that favors healing over regeneration.

The conceptual change suggested by these results is important. Regeneration would not be a capacity completely absent in mammals, but rather a dynamic state that depends on factors such as tissue stiffness, extracellular matrix composition, oxygen availability and epigenetic regulation.

However, it is advisable to be cautious. Complete limb regeneration in mammals has not been achieved in these studies. The works focus on experimental models – such as the regeneration of the fingertip or tissues grown in the laboratory – and mainly analyze the initial phases of the process.