Rev-erb-α antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice
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View abstract on PubMed
Summary
This summary is machine-generated.Aging impairs circadian rhythms, increasing susceptibility to bacterial respiratory infections like Streptococcus pneumoniae. Restoring circadian function in elderly mice improved resistance to infection.
Area Of Science
- Immunology
- Chronobiology
- Microbiology
Background
- Circadian rhythms regulate daily physiological, metabolic, and immune functions.
- Age-related decline in circadian rhythms may increase susceptibility to infections.
- Streptococcus pneumoniae is a common cause of bacterial respiratory tract infections.
Purpose Of The Study
- To investigate the association between age-related circadian rhythm impairments and susceptibility to bacterial respiratory infections.
- To identify specific molecular pathways affected by aging in the context of circadian control of host defense.
Main Methods
- Comparative analysis of Streptococcus pneumoniae infection susceptibility and time-of-day variations in young-adult versus elderly mice.
- Lung circadian transcriptome analysis to identify age-associated alterations in gene expression patterns.
- Investigation of the interaction between the clock component Rev-erb-α and the apelinergic axis in host defense.
- Pharmacological intervention targeting Rev-erb-α in elderly mice.
Main Results
- Elderly mice exhibited altered time-of-day differences in controlling Streptococcus pneumoniae infection compared to young-adult mice.
- Aging disrupted daily gene expression oscillations in the lung, rendering some pathways non-rhythmic or time-shifted.
- Circadian expression of Rev-erb-α and the apelin/apelin receptor pathway was altered in elderly mice.
- An interaction between Rev-erb-α and the apelinergic axis was identified as crucial for host defense against S. pneumoniae in young-adult mice.
- Pharmacological repression of Rev-erb-α enhanced resistance to pneumococcal infection in elderly mice.
Conclusions
- Age-associated impairments in circadian rhythms play a causative role in increased susceptibility to respiratory infections.
- The circadian regulation of host defense mechanisms, particularly involving Rev-erb-α and the apelinergic axis, is compromised with aging.
- Targeting circadian pathways, such as Rev-erb-α, may offer a novel therapeutic strategy to enhance resistance to respiratory infections in the elderly.
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