Fight Aging!

The endothelium lines the interior of blood vessels, and endothelial dysfunction is a feature of aging. Inflammation and changed cell behavior in the endothelium contributions to the formation of atherosclerotic lesions, as well being disruptive of normal management of blood flow by constriction and dilation. A rising burden of cellular senescence in the endothelium is thought to contribute to this age-related dysfunction of the tissue, and thus senolytic treatments to selectively destroy these errant cells are under consideration as a means of treatment. Given the sizable funding devoted to this part of the field in recent years, it isn't surprising to see scientists in search of novel senolytic approaches, ones that may be more tissue-specific and or more effective in specific tissues than the first generation small molecule treatments like the combination of dasatinib and quercetin.

Aging is the major risk factor for chronic disease development. Cellular senescence is a key mechanism that triggers or contributes to age-related phenotypes and pathologies. The endothelium, a single layer of cells lining the inner surface of a blood vessel, is a critical interface between blood and all tissues. Many studies report a link between endothelial cell senescence, inflammation, and diabetic vascular diseases.

Here we identify, using combined advanced AI and machine learning, the Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1B (DYRK1B) protein as a possible senolytic target for senescent endothelial cells. We demonstrate that upon induction of senescence in vitro DYRK1B expression is increased in endothelial cells and localized at adherens junctions where it impairs their proper organization and functions. DYRK1B knock-down or inhibition restores endothelial barrier properties and collective behavior. DYRK1B is therefore a possible target to counteract diabetes-associated vascular diseases linked to endothelial cell senescence.

Link: https://doi.org/10.1016/j.mad.2023.111836