Scientists have known for decades that special cells exist in human intestines. The intestines are one of the few hotspots in the body where some cells, called adult stem cells, stay forever young.
But it was only five years ago that researchers realised that fruit flies have similar stem cells in their intestines. Now this nascent area of research has turned up fascinating findings that may redefine the way we think about our own intestines.
It came from the crypt
Stem cells are needed wherever new cells need to be born, and this is certainly true of the intestines. Every few days the cells lining our intestines are flushed out and replaced. This is vital because of the nature of where these cells work - constantly exposed to digestive enzymes and wear and tear by the passage of waste.
In humans, these stem cell nurseries are called (perhaps counter-intuitively) crypts. The crypts are essentially small pockets in the intestinal lining, which are densely peppered over the length of the intestines.
Stem cells in human intestines have, however, been largely studied not for their specific qualities but rather as a model system of basic biology. The huge cell turnover in the intestines has attracted the interest of biologists who want to study therapeutic uses for adult stem cells.
Tiny fly, big intestines
Two recent studies on fruit flies may, however, reveal a much larger role for these stem cells than previously realised.
The first study, published in October, reported that these stem cells can detect food intake and respond by growing or shrinking the size of the intestines. Dr Lucy O’Brien and colleagues at the University of California-Berkeley compared the intestines of fruit flies four days after they metamorphosed into adults. One group of flies underwent forced fasting for that period and the other had an all-you-can-eat buffet of yeast paste.
At the end of four days, they compared the intestines of both groups. They found that the fed flies had visibly larger intestines, with more than three times as many cells as the intestines of the starved flies. The source of these new cells was the intestinal stem cells, which had produced more new cells in response to food.
Other animals are known to flex their guts in this way. For instance, the intestines of squirrels shrink by two-thirds during hibernation and re-expand after awakening. The human small intestine also expands and contracts by way of stem cells, though the causes behind this are less well understood.
The mechanism found in fruit flies may therefore prompt further investigation of the way human intestines respond to eating, and to overeating. Alongside the digestive system’s recognised contributors to diabetes and obesity – including hormones and gut bacteria – gut stem cells may be shaping human guts to eat more and extract more calories.
Forever young
A second study on fruit fly intestinal stem cells was published last month. It described a genetic tweak to these cells that increased lifespan in fruit flies by 50 per cent.
It has been well-documented that animals on a restricted-calorie diet live longer than average. For instance, mice kept on a diet with about ⅔ their normal calories live 30 or 40 percent longer than usual. The diet apparently protects mice from degenerative diseases which may be why they live longer. Not much is known about the precise mechanism that causes this, but scientists have found that cells of calorie-restricted animals contain more mitochondria, the structures that power the cell.
In mammals and fruit flies, a gene called PGC-1 regulates the number of these cellular power plants. So the team of researchers at the Salk Institute for Biological Studies decided to see if they could manipulate the gene directly in intestinal stem cells to increase the flies’ lifespan.
They found that by boosting the activity of PGC-1, the flies’ cells had greater numbers of mitochondria, and their intestines were healthier into old age. The flies lived between 20 and 50 per cent longer than unmodified flies.
That finding suggests a new importance for the human intestines as a key organ in ageing. Perhaps PGC-1 could have similar lifespan-lengthening possibilities in humans; or, indeed, other treatments targeted to intestinal stem cells could have a similar effect.
After many years in the crypt, perhaps now it’s intestinal stem cells’ day in the sun.
Image by Max xx via Flickr