Transplanted Brain Cells Can Outlast The Body's Biological Clock

The problem with cells is that they have an expiry date. They can only replicate so many times before they hit a biologically predetermined limit and sputter out. But a recent study by neuroscientist Lorenzo Magrassi from the University of Pavia in Italy shows that mammalian neurons are not subject to this kind of replicative aging and, when introduced into a longer-lived organism, will keep on living long after the expected expiry date. The maximum lifespan of these brain cells is still not known, but Magrassi's discovery could have serious implications for the treatment of neurodegenerative diseases — and possibly even life-extending therapies as well.

Working with Ketty Leto and Ferdinando Rossi (both from the University of Turin), Magrassi devised a rather creative experiment. The short version is that precursor brain cells were taken from mice and transplanted into rats (which is incredible unto itself), resulting in the doubling of the expected lifespan of the neurons.

Transplanted Brain Cells Can Outlast The Body's Biological Clock

In terms of the details, the researchers transplanted cerebellar precursors that were pulled from embryonic mice into the brains of young — but longer-living — rats. The scientists did so by inserting a glass microneedle through the abdomens of anesthetized pregnant mice. And to track the neurons, the team injected green fluorescent protein (GFP) into the precursors (thereby allowing them to differentiate mice and rat cells at the end of the experiment).

As the young rats matured, these donor cells differentiated into their various neuronal types and integrated themselves quite nicely within the rat's cerebellum. Interestingly, these cells retained the unique physical characteristics indicative of their mice origin (they were smaller) — but it didn't prove to be a problem for the rats.

Magrassi paid particular attention to Purkinje cells (PCs), of which 40% tend to die off in mice long before they die of old age. The Wistar rats, on the other hand, only lose about 10% at the same stage.

And here's where the experiment got interesting. Normally, all of these brain cells would die once a mouse reaches the 18-month mark (which is the average lifespan of this type of mouse); as their bodies start to senesce and fail, so too do the neurons (the conditions in the microenvironment are no longer conducive to neuronal health). Subsequently, Magrassi and his team were curious to see what was going to happen after this critical 18-month mark.

And indeed, these mice neurons — now firmly embedded in the cerebellum of a midlife rat (a "longer-living host") — continued to function normally. In fact, they remained healthy for the entire 36-month lifespan of the rat.

This led Magrassi to state in the ensuing paper that, "in the absence of pathologic conditions, [neuronal] lifespan is limited only by the maximum lifespan of the organism." There is no "predetermined genetic clock," he concluded.

The ensuing question is an obvious one: Given a healthy body (i.e. a fully healthy microenvironment), just how long can these neurons keep on living? Magrassi and his colleagues don't have an answer to this question, but it would certainly make for an interesting follow-up study (for example, transplantation to even longer-lived rats or other mammals).

The experiment also shows that neurons are a special class of cells — cells that aren't subject to the same replicative limits imposed on other types of cells. Consequently, as long as the microenvironment is healthy (which could be maintained by other external interventions), the neurons could conceivably remain healthy for an extended period as well. This bodes well for the development of therapies treating Alzheimer's and Parkinson's, and for life-extending interventions in general.

The entire study can be read at Proceedings of the National Academy of Sciences.

Images: Lorenzo Magrassi.