Senolytic therapies reduced immune cell infiltration in the lungs of aged mice with influenza A, but did not improve illness severity or survival. Despite targeting ageing-related senescence, these short-term treatments failed to reverse immune dysfunction, suggesting senolytics may not offer universal benefits across all respiratory infections in later life.
January 2025 – Ageing Cell
Key takeaways
- Senolytics dampen immune cell influx: Treatments like dasatinib with quercetin, fisetin, and ABT-263 reduced immune cell infiltration in the lungs of aged mice infected with influenza A. However, this suppression included beneficial immune cells such as T cells and natural killer cells, potentially weakening the host’s antiviral response rather than enhancing recovery
- No improvement in infection outcomes: Despite reducing inflammation-related markers, senolytic treatments did not improve weight loss, clinical symptoms, or survival rates in aged mice. This challenges the assumption that clearing senescent cells universally improves resilience to respiratory infections associated with ageing
- Senescence markers remained unchanged: Short-term senolytic therapy did not significantly reduce senescence markers such as p21 or β-galactosidase activity in the lungs or fat tissue. This suggests that brief dosing regimens may be insufficient to reverse age-related cellular changes, highlighting the need for refined protocols or longer treatments
- Efficacy appears pathogen-specific: Senolytics have shown promise in SARS-CoV-2 models, possibly by reducing ACE2 expression, absent in influenza replication. Their failure to benefit influenza outcomes implies their effects may be specific to certain viral mechanisms and not broadly applicable to all age-exacerbated infections
Read the article at: Luna, Adrian, et al. “Senolytic treatment attenuates immune cell infiltration without improving IAV outcomes in aged mice.” Aging Cell, 2025, https://doi.org/10.1111/acel.14437.