Fight Aging!

As the research community continues to improve our understanding of the mechanisms of regeneration, ever more potential ways to improve healing and regrowth should emerge as a result. Stem cell therapies are one outcome of this research: having found the cells that do much of the work to keep our tissues in shape, we can now think about directing them, growing more of them, reversing their decline in aging, transplanting them between individuals, and so forth. But this is far from the only type of approach that might arise. Evolution doesn't tend to produce systems that are optimized for the best possible outcome for individuals: we can see that in the ease with which researchers can adjust any one of a handful of genes to extend healthy life in laboratory mice. Similarly we should expect there to exist numerous small genetic or metabolic changes that produce improved regeneration in mammals, but which have not been selected for by evolution in most species.

On this topic a couple of research results were publicized today, illustrating the sort of work that kicks off further investigations aimed at improving human regeneration, either globally or in specific tissue types:

Scientists identify clue to regrowing nerve cells

Axons are the branches of nerve cells that send messages. They typically are much longer and more vulnerable to injury than dendrites, the branches that receive messages. In the peripheral nervous system cells sometimes naturally regenerate damaged axons. But in the central nervous system, comprised of the brain and spinal cord, injured nerve cells typically do not replace lost axons.

Working with peripheral nervous system cells grown in the laboratory, [researchers] severed the cells' axons. [They] learned that this causes a surge of calcium to travel backward along the axon to the body of the cell. The surge is the first step in a series of reactions that activate axon repair mechanisms. In peripheral nerve cells, one of the most important steps in this chain reaction is the release of a protein, HDAC5, from the cell nucleus, the central compartment where DNA is kept. The researchers learned that after leaving the nucleus, HDAC5 turns on a number of genes involved in the regrowth process. HDAC5 also travels to the site of the injury to assist in the creation of microtubules, rigid tubes that act as support structures for the cell and help establish the structure of the replacement axon.

When the researchers genetically modified the HDAC5 gene to keep its protein trapped in the nuclei of peripheral nerve cells, axons did not regenerate in cell cultures. The scientists also showed they could encourage axon regrowth in cell cultures and in animals by dosing the cells with drugs that made it easier for HDAC5 to leave the nucleus. When the scientists looked for the same chain reaction in central nervous system cells, they found that HDAC5 never left the nuclei of the cells and did not travel to the site of the injury. They believe that failure to get this essential player out of the nucleus may be one of the most important reasons why central nervous system cells do not regenerate axons.

"This gives us the hope that if we can find ways to manipulate this system in brain and spinal cord neurons, we can help the cells of the central nervous system regrow lost branches. We're working on that now."

Researchers reactivate gene to rejuvenate tissue repair

[An] RNA-binding protein, Lin28a, promotes tissue repair by reactivating a metabolic state reminiscent of the juvenile developmental stage. [Researchers] showed that reactivation of Lin28a - a gene that is normally turned on in fetal but not adult tissues - substantially improved hair regrowth and accelerated tissue repair after ear and digit injuries. "Our work found that Lin28a promotes regeneration through a metabolic mechanism. This finding opens up an exciting possibility that metabolism could be modulated to improve tissue repair, whereby metabolic drugs could be employed to promote regeneration."