Senolytic treatment with dasatinib and quercetin does not improve overall influenza responses in aged mice

Area of Science:

• Immunology
• Gerontology
• Virology

Background:

• Aging increases susceptibility to severe influenza (flu) outcomes.
• Cellular senescence, an accumulation of senescent cells, is a hallmark of aging and a contributor to age-related diseases.
• Senolytics, drugs targeting senescent cells, show promise in mitigating age-related declines, but their impact on the aged immune system is largely unknown.

Purpose of the Study:

• To investigate whether senolytic treatment can improve age-related immune deficits in response to influenza infection.
• To assess the efficacy of dasatinib and quercetin (D + Q) in clearing senescent cells and enhancing immune function in aged mice.

Main Methods:

• Aged mice (18-20 months) were treated with a combination of dasatinib and quercetin (D + Q) to eliminate senescent cells.
• Mice were subsequently infected with influenza to comprehensively profile immune responses.
• Assays included evaluation of weight loss, viral load, CD8 T-cell infiltration, antibody production, memory T-cell development, and recall responses.

Main Results:

• Senolytic treatment with D + Q did not improve any measured aspects of the immune response to influenza infection in aged mice.
• No significant differences were observed in weight loss, viral load, or CD8 T-cell infiltration between treated and untreated aged mice.
• Antibody production, memory T-cell development, and recall responses following pathogen reencounter were not enhanced by the senolytic treatment.

Conclusions:

• The senolytic combination of dasatinib and quercetin (D + Q) did not ameliorate age-related deficits in the immune response to influenza infection.
• These findings suggest that D + Q may not be an effective senolytic strategy for improving aged immune function against flu.
• Further research is needed to identify senolytic treatments that can effectively bolster the aging immune system.