Scientists at the Salk institute have discovered that increasing expression of a gene called PCG1 in fruit flies reduced signs of aging. The effect was demonstrated in the lining of the insect’s intestine and mimicked the effects of caloric restriction. This gene is also found in humans.
Caloric restriction is found to increase lifespan across multiple species including insects and mammals. The method reduces aging through multiple suspected mechanisms. One effect, pinpointed in this study, is to increase the number and health of mitochondria in animals’ cells. Mitochondria are the powerplants of cells, they consume oxygen to produce energy in the form of ATP. Since they deal with constant high throughput of oxygen, they also generate reactive oxygen free radicals, that damage the cells and the mitochronia themselves leading to senescence and aging.
PCG-1, both in the fruit flies and humans, functions to regulate the number of mitochondria a cell produces.
In the current experiment, the researchers used genetic methods to increase expression of the PCG-1 gene. They targetted the flies’ intestinal stem cells.
As a result of this intervention, the flies lives 50% longer. Their intestines had more mitochrondria and reduced aging.
“Their intestines were beautiful,” says Christopher L. Koehler, a doctoral-student at University of California San Diego who conducts research in Jones’ laboratory. “The flies with the modified gene activity were much more active and robust than the other flies.”
It is interesting how improved youthfulness of a single organ, the gut, proved to increase the lifespan of the whole organism. This may be due to the gut’s role in immunity, as it is in constant contact with bacteria in its lining. As the gut ages it can become suscpetible to attack from pathological bacteria living there. Also it is a high turnover tissue.
It is important to note the researchers did not find if PCG-1 expression was increased throughout the whole organism that they lived longer.
“Our ﬁndings point to the possibility that alterations in PGC-1 activity in high-turnover tissues, such as the intestine, may be an important determinant of longevity in mammals,” write the authors.
“It will be interesting to determine whether PGC-1 family members in other species also regulate tissue homeostasis in high-turnover tissues such as intestine,” they added.
Cell Metabolism 14, 623–634, November 2, 2011