Regeneration in the adult organism - a cure for ageing? - Malcolm Maden
The most amazing organ regenerative ability is displayed by the Urodele amphibians such as axolotls which can regenerate brains, spinal cord, limbs, tails, heart, lower jaw and other structures. There are many reasons for studying regenerative mechanisms in these organisms and one of the most intriguing may be the relation between regeneration and ageing. How old are the cells of a regenerated organ – the same as the host animal or is age reset in a dedifferentiated multipotent stem cell? Nothing is known about this phenomenon apart from the demonstration that regenerative ability does not decline with age in Urodeles – the quality of the last regenerate is as good as the first. Even without this knowledge, the ability to induce organ regeneration in humans would have a huge impact on ageing and longevity. We have had some success at inducing regeneration in mammals by extrapolating from our understanding of axolotl regeneration, in particular concerning one developmental signaling molecule, retinoic acid. This molecule is critically required for limb development, limb regeneration, heart regeneration and when administered in excess induces the duplication of limbs. Its mechanism of action and targets in the nucleus are gradually being revealed and it interacts with other developmental signaling pathways. Most importantly we have shown that retinoic acid can induce a regenerative response in mammalian organs which cannot normally regenerate such as the lung and the spinal cord. We have therefore referred to this molecule as a regeneration-inducing molecule. Our recent studies have also revealed the role of retinoic acid in neurodegenerative diseases such as Alzheimer’s disease and in a mouse model of this disease it has the remarkable effect of reducing plaque load and the levels of the toxic Ab peptide in the brain. Retinoic acid may thus really have life-extending properties and we anticipate that further research may also give us insights into the ageing process itself.