The world’s population of ages 60 and older is projected to nearly double by the year 2050. This, along with the statistic that seven million people in the US live with dementia, is alarming. The Symposium Session “The State of the Science Linking Environmental Chemicals to Age-Related Neurocognitive Disease” opened with a crash course on air pollution and the complexity of particulate matter as a mixture. With particulate matter, the size of the particles is directly linked to their potential for causing health problems. The mechanism of effect, however, is unknown.
The first speaker, Allison Kupsco from Columbia University, introduced extracellular RNA (exRNA) as a biomarker. exRNA has a role in intercellular communication. She noted that microRNAs make up a large population of exRNA and may regulate more than 60% of human genes. Dr. Kupsco spoke about the Normative Aging Study (NAS) and the effects of air pollution on cognition in the study. An exRNA analysis was done on NAS samples, and short-term air pollutants were associated with many microRNAs and some microRNAs were associated with Alzheimer’s disease in the cerebrospinal fluid in the samples taken in 1999.
In the NAS study, another biomarker was studied of tRNA fragments, or tRFs, which function similar to miRNAs. Dr. Kupsco introduced the concept of tRF mapping, where they identified thousands of tRNAs and 200 unique tRFS, which were detected in 70% of the NAS samples. The overall question of this talk was what ramifications are associated with tRNAs and what their actual function is. Dr. Kupsco is focused on uncovering this answer in her research.
Quan Lu, from the Harvard T.H. Chan School of Public Health, introduced extracellular vesicles (EVs) as a biomarker for aging and age-related neurodegenerative diseases. EVs are both biomarkers and functional mediators for environmental health and disease, and the amount and content of EVs change in response to environmental exposure and in disease. A major challenge with EVs is their heterogenous nature, but Dr. Lu is addressing this by isolating EVs secreted by specific tissues in mice. The talk identified markers of brain-derived EVs by proteomics, and a comparison was done with brain-derived EVs in young vs. old mice to identify changes in EVs during aging. EVs are a new and hot topic in neurodegenerative disease, and Dr. Lu’s research in the field was quite interesting.
Pamela Lein, from the University of California Davis, was next, and she spoke on air pollution in Alzheimer’s disease (AD) phenotypes. Fewer than 5% of AD cases are based solely on genetics, and environmental risk factors for AD can be remediated. Dr. Lein models near roadway exposures for traffic-related air pollution (TRAP). Her lab built a vivarium near a roadway so rats would get the same exposure as humans. In a TgF344-AD rat model, Dr. Lein found that TRAP exposure recapitulated AD phenotypes and increased AD pathology. It also promoted cognitive defects in male wildtype rats in a contextual fear conditioning assay. Chronic exposure to TRAP promoted AD phenotypes, an important finding in such a realistic exposure scenario.
Lisa Truong, from Oregon State University, spoke next about her model, the zebrafish. She introduced several behavioral assays that can be done over the life of the zebrafish and shared her research on toxicants like benzo[a]pyrene. Her lab recently developed some new instruments that are able to rapidly screen behaviors across all life stages. Behavioral phenotyping is no longer limited to the early stages of life.
Finally, the session circled back to air pollution with speaker Cavin Ward-Caviness, from the US EPA, who shared research on epigenetic aging. This part of the talk switched back to human-centered research about air pollution and social determinants of health and their relation to age-related outcomes. Epigenetic aging is determining the biological age of a tissue using DNA methylation, and the overall question was how environment is impacting aging biomarkers. Dr. Ward-Caviness did research on an in vivo housing conditions model in mice, where mice were given depleted or enriched housing, and found differences in body fat relative to housing type. This highlighted a possible in vivo model for health span.
Air pollution seemed to be a major indicator of age-related disease, and this session highlighted the importance of its research. A diverse array of speakers spoke about both model organism and human-centered research—from toxicants to epigenetics. This early morning session surely delivered on the importance of studying age-related neurocognitive disease.
This blog reports on the Symposium Session titled “The State of the Science Linking Environmental Chemicals to Age-Related Neurocognitive Disease" that was held during the 2024 SOT Annual Meeting and ToxExpo. An on-demand recording of this session is available for meeting registrants on the SOT Online Planner and SOT Event App.
This blog was prepared by an SOT Reporter and represents the views of the author. SOT Reporters are SOT members who volunteer to write about sessions and events in which they participate during the SOT Annual Meeting and ToxExpo. SOT does not propose or endorse any position by posting this article. If you are interested in participating in the SOT Reporter program in the future, please email SOT Headquarters.
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