More Details to Show How the Clearance of Senescent Cells Impacts Vascular Aging
Accumulation of senescent cells is one of the root causes of aging. Now that the scientific community has the means to selectively remove these unwanted cells, such as via the use of senolytic drugs, and now that funding has picked up for this field, researchers are rapidly quantifying specific links to the pathology of age-related disease. For example, earlier this year researchers demonstrated that clearance of senescent cells produces significant benefits to vascular health, slowing or reversing many of the aspects of aging in blood vessels, such as calcification and growth of atherosclerotic plaque. This more recently published open access paper on the same topic adds more details to the picture:
Risk factors for ischemic heart disease include hypercholesterolemia, arterial stiffness, chronic inflammation, hypertension, metabolic syndrome, and aging. Importantly, these risk factors contribute to impaired endothelial function, which can contribute to arterial remodeling and accelerate atherosclerotic plaque formation and expansion. Recent work suggests senescent cell burden can be dramatically increased by chronological aging, and short-term treatment with 'senolytic' drugs alleviates several aging-related phenotypes. However, effects of long-term senescent cell clearance on vascular reactivity and structure with aging or chronic hypercholesterolemia remain unknown. To determine whether senolytic treatment with dasatinib and quercetin (D+Q) reduces senescent cell burden and improves vascular function in aged mice, we maintained C57BL/6J mice on standard chow for 24 months, and then initiated D+Q once monthly for 3 months.
Senolytic treatment resulted in significant reductions in senescent cell markers in the medial layer of aorta from aged and hypercholesterolemic mice, but not in intimal atherosclerotic plaques. While senolytic treatment significantly improved vasomotor function in both groups of mice, this was due to increases in nitric oxide bioavailability in aged mice and increases in sensitivity to NO donors in hypercholesterolemic mice. Senolytics tended to reduce aortic calcification and osteogenic signaling in aged mice, but both were significantly reduced by senolytic treatment in hypercholesterolemic mice. Intimal plaque fibrosis was not changed appreciably by chronic senolytic treatment. This is the first study to demonstrate that chronic clearance of senescent cells improves established vascular phenotypes associated with aging and chronic hypercholesterolemia, and may be a viable therapeutic intervention to reduce morbidity and mortality from cardiovascular diseases.
Link: http://onlinelibrary.wiley.com/doi/10.1111/acel.12458/full