The Fear of Fat

Obesity-induced anxiety might be caused by the accumulation of fatty senescent glial cells – and cleared by senolytics.

The link between cellular senescence and the pro-inflammatory signaling networks that contribute to aging and age-related diseases is well established (1). But what drives the link between senescence and neuropsychiatric disorders, such as obesity-induced anxiety – a common condition with serious implications that range from social isolation to suicidal ideation?

To find out more, a multinational team of researchers induced obesity in mouse models using a high-fat diet feeding regimen (2). As expected, the obese mice showed heightened levels of anxiety. Next, the team studied the makeup of their brains and found an accumulation of senescent glial cells with excessive fat deposits in proximity to the lateral ventricle – a highly neurogenic region.

Encouraged, the researchers decided to test a hypothesis – that the fatty senescent cells were directly responsible for the heightened anxiety seen in the mice. The researchers used two senolytic drugs – dastanib and quercetin – to clear the senescent cells from the brains of the mice, and found that symptoms of anxiety were alleviated. The team also noted that neurogenesis – repressed by the presence of the senescent cells – also recovered.

“Our data demonstrating a link between obesity, senescence, and anxiety-like behavior provide critical support for the potential feasibility of administering senolytics to treat obesity-associated anxiety-like behavior,” state the authors.