Neurometabolomic impacts of wood smoke and protective benefits of anti-aging therapeutics in aged female C57BL/6J mice.

BACKGROUND: Wildland fires have become progressively more extensive over the past 30 years in the United States, routinely generating smoke that deteriorates air quality for most of the country. We explored the neurometabolomic impact of biomass-derived smoke on older (18 months) female C57BL/6J mice, both acutely and after 10 weeks of recovery from exposures. METHODS: Mice were exposed to wood smoke (WS) 4 hours/day, every other day, for 2 weeks (7 exposures total) to an average concentration of 448 μg particulate matter (PM)/m(3) per exposure. One group was euthanized 24 hours after the last exposure. Other groups were then placed on 1 of 4 treatment regimens for 10 weeks after wood smoke exposures: vehicle; resveratrol in chow plus nicotinamide mononucleotide in water (RNMN); senolytics via gavage (dasatanib + quercetin; DQ); or both RNMN with DQ (RNDQ). RESULTS: Among the findings, the aging from 18 months to 21 months was associated with the greatest metabolic shift, including changes in nicotinamide metabolism, with WS exposure effects that were relatively modest. WS caused a reduction in NAD + within the prefrontal cortex immediately after exposure and a long-term reduction in serotonin that persisted for 10 weeks. The serotonin reductions were corroborated by behavioral changes, including increased immobility in a forced swim test, and neuroinflammatory markers that persisted for 10 weeks. RNMN had the most beneficial effects after WS exposure, while RNDQ caused markers of brain aging to be upregulated within WS-exposed mice. DISCUSSION: Taken together, these findings highlight the persistent neurometabolomic and behavioral effects of woodsmoke exposure in an aged mouse model. Further examination is necessary to determine the age-specific and species-determinant response pathways and duration before complete resolution occurs.