A new study has shown that it may be possible to treat renal fibrosis, an age-related disease, by lengthening telomeres.
Previous research had shown it was that lengthening telomeres successfully treated pulmonary fibrosis and infarctions in mice.
Renal fibrosis is the leading cause of kidney failure, treatable only with dialysis. Moderate renal fibrosis is present in some 11% of people over 65, and is a predictor of the severity of renal failure. Telomeres are proteins at the end of chromosomes that maintain genetic integrity during cellular division. They shorten over time, eventually to the point where they are too short for cells to divide, becoming senescent. Telomere lengthening, eg through hyperbaric oxygen therapy, has been suggested as a way to reverse many age-related declines.
While short telomeres were by themselves not enough to cause renal fibrosis, the researchers found that mice with short telomeres developed it when they were exposed to small amounts of toxin, mimicking the environmental toxins people are exposed to over their lives. Mice that also lacked a certain protein needed for telomere function, Trf1, developed renal fibrosis, showing that telomeres are indeed involved in proper kidney function.
Since genes involved in epithelial-to-mesenchymal transition are overexpressed in patients with kidney failure, the researchers looked for this in mice with short telomeres. And “we found that short telomeres induce changes in the expression of genes involved in EMT.”
As a final demonstration of the importance of telomeres in kidney fibrosis, the authors cultured kidney cells in which they expressed the gene for the telomerase enzyme, which elongates telomeres. In these cells with restored telomeres, the epithelial-to-mesenchymal transition program returned to normal, and the cells regained their healthy, pre-fibrosis appearance.
“As short telomeres accumulate with ageing in the organism, it is tempting to speculate that pathological EMT programmes associated with ageing, such as cancer and different types of tissue fibrosis, may be originated at least in part by the presence of short telomeres,” the authors conclude.
Source: News-Medical.Net
