Researchers here show that a form of ultrasound stimulation can be used to provoke lingering senescent cells into behavior that increases the pace of immune clearance of these unwanted cells. The change in markers of the burden of senescence in skin tissue, a reduction of about a third, is similar to the levels of clearance produced in other organs by first generation senolytic drugs. It is worth noting that the researchers used young mice in their study, and a course of irradiation to produce senescent cells. There are differences in the senescent state resulting from irradiation versus other causes of senescence. Further, the immune system becomes less capable of clearing senescent cells in later life. It is unclear whether this approach would work as well on the natural burden of senescence in old mice.
As emerging therapeutic strategies for aging and age-associated diseases, various biochemical approaches have been developed to selectively remove senescent cells, but how physical stimulus influences senescent cells and its possible application in senolytic therapy has not been reported yet. Here we developed a physical method to selectively stimulate senescent cells via low-intensity pulsed ultrasound (LIPUS) treatment. LIPUS stimulation did not affect the cell cycle, but selectively enhanced secretion of specific cytokines in senescent cells, known as the senescence-associated secretory phenotype (SASP), resulting in enhanced migration of monocytes/macrophages and upregulation of phagocytosis of senescent cells by M1 macrophages.
We found that LIPUS stimulation selectively perturbed the cellular membrane structure in senescent cells, which led to activation of the intracellular reactive oxygen species-dependent p38-NF-κB signaling pathway. Using a UV-induced skin aging mouse model, we confirmed enhanced macrophage infiltration followed by reduced senescent cells after LIPUS treatment. Due to the advantages of ultrasound treatment, such as non-invasiveness, deep penetration capability, and easy application in clinical settings, we expect that our method can be applied to treat various senescence-associated diseases or combined with other established biochemical therapies to enhance efficacy.
Link: https://doi.org/10.1111/acel.14486
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