Extended PPI use accelerates cell aging




Long-term exposure to common nonprescription heartburn medication caused cells in blood vessels to age faster in a laboratory setting, compared with exposure to placebo, according to data published online May 10 in the American Heart Association’s journal, Circulation Research.

Proton pump inhibitors (PPIs) are routinely sold over the counter, mainly for gastroesophageal reflux disease, but data suggest that as much as 70% of PPI use is inappropriate, according to Gautham Yepuri, Ph.D., a postdoctoral research fellow at Houston Methodist Research Institute, and his associates.

The researchers examined how long-term use of PPIs might increase the risk of serious illnesses by studying cultured human microvascular endothelial cells (Circulation Research 2016 [doi: 10.1161/circresaha.116.308807]). They hypothesized that PPIs contribute to endothelial dysfunction, which in turn is associated with the development of conditions including heart disease, kidney disease, and dementia. They compared endothelial cells exposed to a PPI with those exposed to placebo.

Endothelial cells exposed to the PPI esomeprazole (ESO) showed reduced fluorescence “consistent with an increase in lysosomal pH,” the researchers wrote. In addition, endothelial cells treated with ESO demonstrated increased cell senescence and impaired endothelial function. PPI exposure also was associated with significant telomere shortening.

“This adverse effect appears to be due to an inhibition of lysosomal acidification and subsequent impairment of proteostasis,” the researchers noted. “In the presence of consistent epidemiological evidence of harm and a unifying mechanism for the disparate disorders linked to PPI use, and with the knowledge that PPIs are being used by millions of people for indications and durations that were never tested or approved, it is time for the pharmaceutical industry and regulatory agencies to revisit the specificity and the safety of these agents,” they stated. However, clinical studies are needed to determine whether the damage seen in the laboratory occurs in the body as well.

The study was funded in part by the National Institutes of Health and the Swiss National Science Foundation. The researchers reported having no financial conflicts to disclose.

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