New treatments for progeria

extremely rare and fatal autosomal dominant genetic condition that causes accelerated aging in children. Typically, those born with progeria live to their midteens or early twenties. HGPS is caused by accumulation of progerin (a protein altered during normal aging) at the nuclear envelope. Most people with HGPS harbor a single nucleotide substitution (GGCGGT; G608G) within exon 11 of the gene encoding lamin A [1,2]. This mutation activates a cryptic splice-donor site, leading ultimately to a truncated, permanently farnesylated isoform of prelamin A (progerin) that results in a dimorphic nuclear phenotype in HGPS. Reversion of the HGPS mutation in mice using CRISPCas9 extends longevity, highlighting a potential therapeutic approach [1,2]. However, this treatment strategy is a long way from being applicable in humans. Therefore, improving the main symptoms, which stem from production and accumulation of progerin, is the main treatment strategy for this devastating disease [3,4]. However, a recent study describes an alternative strategy for treatment of HGPS [5]. As in humans, mice with HGPS display excessive vascular calcification, a common clinical manifestation associated with aging, diabetes, and chronic kidney disease. This incremental increase in calcium deposition on the aortic wall in HGPS mice is due to deficiency of extracellular pyrophosphate [6], a potent endogenous inhibitor of calcification [7]. This reduction in extracellular pyrophosphate levels in HGPS mice is a consequence of Editorial