Proton Pump Inhibitors Accelerate Cellular Aging

By Megan Brooks

May 12, 2016

NEW YORK (Reuters Health) - A new study suggests that chronic use of a proton pump inhibitor (PPI) accelerates aging of endothelial cells.

PPIs impair the ability of the lysosomes in vascular cells to generate acid. Lysosomes function as "garbage disposals for the vascular cells (and) they can't work well if they can't generate acid," lead investigator Dr. John Cooke of Houston Methodist Research Institute in Texas told Reuters Health by email.

"Doctors have been giving the PPIs with the understanding that these drugs are specific for the acid pump in the stomach. What we have found is that another acid pump is affected, and this causes 'garbage' (damaged proteins) to aggregate in the cells, (which) causes the cells to age faster," he explained.

"This study provides a plausible unifying mechanism for accumulating reports that PPI users are at increased risk for heart attack, kidney problems, and dementia," Dr. Cooke said.

The study is scheduled for publication May 10 in Circulation as a Brief Ultrarapid Communication.

In cultured human microvascular endothelial cells, Dr. Cooke and his colleagues observed that chronic exposure to clinically relevant concentrations of the PPI esomeprazole accelerates endothelial aging by impairing lysosomal function and proteostasis, leading to an increase in oxidative stress, endothelial dysfunction, and senescence by reducing telomere length.

"The health of our blood vessels is necessary for normal functioning of our heart, brain, and kidneys. Damage to the lining of our blood vessels could lead to heart attack, dementia and renal failure. The pharmaceutical industry and regulatory authorities should reconsider the use of these agents without medical supervision. Physicians should be more cautious in their prescription of these drugs," Dr. Cooke told Reuters Health.

"Unless otherwise indicated, physicians should consider PPIs only for short-term use for relief of symptoms of GERD (gastroesophageal reflux disease), since we now have a 'smoking gun' that helps explain the consistent observational evidence of increased risk," he added in a news release.

The researchers note that they have not tested the full range of PPIs that are commercially available and have not determined if the effect of the PPIs to accelerate aging of human endothelial cells occurs in vivo.

"We urgently need to study the effects of these drugs on vascular health, which we are preparing to do at Houston Methodist Research Institute," Dr. Cooke said.

The study had no commercial funding and the authors have no relevant disclosures.


Circulation 2016.