Image courtesy of NIH
Chronic exposure to proton pump inhibitors (PPIs) accelerates biological aging in human endothelial cells, according to preclinical research.
Investigators said this finding, published in Circulation Research, supports recent epidemiological and retrospective studies that revealed associations between the long-term use of PPIs and an increased risk of heart attack, renal failure, and dementia.
“When we exposed human endothelial cells over a period of time to these PPIs, we observed accelerated aging of the cells,” said John P. Cooke, MD, PhD, of the Houston Methodist Research Institute in Texas.
“The PPIs also reduce acidity in lysosomes of the endothelial cell. The lysosomes are like cellular garbage disposals and need acid to work properly. We observed cellular garbage accumulating in the endothelial cells, which sped up the aging process.”
Dr Cooke suspects this may be the unifying mechanism that explains the increased risk of heart attack, renal failure, and dementia observed in long-term PPI users.
“These drugs do not seem to adversely affect the heart and blood vessels when taken for a few weeks,” he said. “However, we urgently need studies to assess the impact of long-term use of these drugs on vascular health in a broad patient population. We also need to consider if these drugs should be so accessible without medical supervision.”
Dr Cooke and his colleagues noted that, while PPIs like esomeprazole (Nexium) were shown to affect vascular aging, H2 blockers like ranitidine (Zantac) did not adversely affect the endothelium.
Therefore, other approaches to long-term treatment that should be considered for gastroesophageal reflux disease include H2 antagonists, lifestyle modifications, and, in severe cases, surgical approaches.
The investigators also pointed out that this study had some limitations. Although two different PPIs were tested, only one of these, esomeprazole, is commercially available.
In addition, the study did not show how PPIs actually impair the lysosome’s ability to produce enough acid to clear waste.
Finally, since this study was conducted in a laboratory setting, it did not show whether PPIs act in the same way within the human body as they do in vitro.
