Senolytics Don't Help Aged Mice Resist Influenza Infection
In mice, senolytic therapies to clear senescent cells seem such a panacea for age-related conditions that it is always interesting to see evidence for an aspect of aging that is not helped by removal of a portion of the burden of lingering senescent cells. Here, researchers show that senolytics do nothing to help aged mice resist influenza infection if they are administered during or shortly before exposure. Based on what is known of the role of cellular senescence in aging, one would expect an aged mouse that has been treated once with senolytics to later be more resilient to stresses of all sorts, but it likely takes some time for the benefits to be realized, longer than was allowed for here.
Aging is a major risk factor for poor outcomes following respiratory infections. In animal models, the most severe outcomes of respiratory infections in older hosts have been associated with an increased burden of senescent cells that accumulate over time with age and create a hyperinflammatory response. Although studies using coronavirus animal models have demonstrated that removal of senescent cells with senolytics, a class of drugs that selectively kills senescent cells, resulted in reduced lung damage and increased survival, little is known about the role that senescent cells play in the outcome of influenza A viral (IAV) infections in aged mice.
Here, we tested if the aged mice survival or weight loss IAV infections could be improved using three different senolytic regimens. We found that neither dasatinib plus quercetin, fisetin, nor ABT-263 improved outcomes. Furthermore, both dasatanib plus quercetin and fisetin treatments further suppressed immune infiltration than aging alone. Additionally, our data show that the short-term senolytic agents do not reduce senescent markers in our aged mouse model. These findings suggest that acute senolytic treatments do not universally reverse aging related immune phenotype against all respiratory viral infections.
Do all mammals experience Thymic involution? If so, that is likely the reason senolytics did not help in this case.