Mechanism for Senescent Cell Removal Revealed

A study in mice by researchers at Georgetown Lombardi Comprehensive Cancer Center has found that stress and tissue damage initiated by angiotensin II, a molecule that is known to increase blood pressure and stiffening in the linings of blood vessels, leads to cellular senescence. The findings published in Frontiers in Cell and Developmental Biology, also report on a novel mechanism for senescent cell removal.

“We’ve known that angiotensin II can lead to hypertension and cellular damage, but our findings show that chronic, stress-induced damage due to slightly elevated blood pressure could be reduced by eliminating senescent cells,” says Irfan Khan, first author. “By preventing the harmful effects of angiotensin II, we revealed a novel mechanism for eliminating senescent cells that could potentially be used to develop targeted drugs to eliminate these cells.”

The researchers chose angiotensin II as the tool to best induce chronic stress because they could regulate its administration and induce a measured stress level similar to that seen in people who see a slow rise in blood pressure over a lifetime. This stress typically results in less flexibility in the lining of blood vessels, which in turn leads to higher blood pressure. The researchers discovered that these effects are particularly pronounced in the kidneys and not in the brain or lungs, which is what they expected when they started their experiments.

“Essentially, we’re building the biological basis for a new therapeutic approach to address the senescence aspect of the disease that has mostly been unexplored and untreated,” says corresponding author Anton Wellstein. Eliminating senescent cells with a tolerable, short-term therapy could potentially alleviate chronic cardiovascular disease and reduce the need for a lifetime of therapy."