A combination of statins and drugs for bone disorders could treat premature-ageing conditions such as Hutchinson-Gilford progeria syndrome (HGPS), reports a study published online in Nature Medicine.
Several forms of human premature aging, including HGPS, are caused by a mutant protein called progerin. Progerin undergoes a biochemical modification known as prenylation, which anchors it to the membrane of the cell nucleus, leading to the disease. Previous studies showed that inhibitors of the enzyme farnesyltransferase (FT), which is responsible for one form of prenylation, eliminate the nuclear abnormalities associated with progerin accumulation and lead to a small improvement of the aging-like characteristics in a mouse model of progeria.
Now, Carlos López-Otín and colleagues show that progerin is also prenylated by the enzyme geranylgeranyltransferase (GGT), which could explain the low efficiency of the FT inhibitors in previous studies. The authors also show that a combination of cholesterol-lowering drugs -- statins -- and drugs for certain bone disorders -- aminobisphosphonates -- prevents the modification of progerin, markedly improving the aging-like characteristics of progeroid mice, and increasing their life span.
These findings point to a new therapeutic approach for HGPS and other premature-aging syndromes.
Carlos López Otín (Universidad de Oviedo, Spain)
Abstract available online.
(C) Nature Medicine press release.
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