Fight Aging!

At this point in the development of senolytic therapies to clear harmful, lingering senescent cells from aged tissues, it is more interesting to find an aspect of aging that isn't improved by removal of senescent cells than to continue adding to the long list of age-related conditions and dysfunctions that are meaningfully reversed by senescent cell clearance. Here, researchers show that measures of the immune response to influenza infection in mice are not improved followed treatment with the senolytic combination of dasatinib and quercetin. This is a perhaps surprising result, given the expectation based on evidence to date that senolytics should improve immune function in later life.

Age is the greatest risk factor for adverse outcomes following influenza infection. The increased burden of senescent cells with age has been identified as a root cause in many diseases of aging and targeting these cells with drugs termed senolytics has shown promise in alleviating many age-related declines across organ systems. However, there is little known whether targeting these cells will improve age-related deficits in the immune system.

Here, we utilized a well characterized senolytic treatment with a combination of dasatinib and quercetin (D + Q) to clear aged (18-20 months) mice of senescent cells prior to influenza infection. We comprehensively profiled immune responses during the primary infection as well as development of immune memory and protection following pathogen reencounter. Senolytic treatment did not improve any aspects of the immune response that were assayed for including: weight loss, viral load, CD8 T-cell infiltration, antibody production, memory T cell development, or recall ability. These results indicate that D + Q may not be an appropriate senolytic to improve aged immune responses to flu infection.

Link: https://doi.org/10.3389/fragi.2023.1212750