Three smokes in the evolution of the human exposome

Three smokes were inhaled during evolution of the human exposome. The first frequent inhalation of pre-H. sapiens was smoke from domestic fires, followed most recently by globally expanding wildfires. Two modern smokes are tobacco and air pollution from fossil fuels of roadway exhaust and power plants. The three smokes derive from partially combusted plant-material. Their microscopic particles of 0.1-10 µm share chemistry of nitrogen and sulfur oxides, and carcinogenic polycyclic hydrocarbons. Tobacco and roadway exhaust increase the risks of lung cancer and dementia, but also childhood adiposity, with supra-additivity. While the basis for these synergies is unknown, air pollution from fossil fuels is being understood in terms of  biochemistry and gene regulation. Rodent and cell models are exposed to size-defined particulate material, e.g. (PM2.5µ) from roadway exhaust air pollution, including standardized diesel exhaust particles. Acute and multi-week exposures cause oxidative stress with compromised glutathione metabolism. Brain responses include increases of the amyloid peptides of Alzheimer’ dementia. Multiple gene responses are mediated by the transcription factors NFkB and Nrf2. Potential protection from the dementia risk of air pollution is a new drug that attenuates an enzyme of amyloid production (GSM-15606) which partly inhibited brain amyloid responses of mice to air pollution components.  Genetic susceptibility to air pollution is increased by ApoE4 in some human populations and  in transgenic mice. Did the Alzheimer resistant ApoE3 allele evolve 200,000 years ago in some relation to its benefit to smoke inhalation? 

Finch, CE. (2018). The Role of Global Air Pollution in Aging and Disease: Reading Smoke Signals. Academic Press.

Trumble, B. C., & Finch, C. E. (2019). The exposome in human evolution: From dust to diesel. The Quarterly Review of Biology, 94(4), 333–394. https://doi.org/10.1086/706768

Finch, C. E., & Thorwald, M. A. (2024). Inhaled pollutants of the Gero-Exposome and later-life health. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 79(7). https://doi.org/10.1093/gerona/glae107

Godoy-Lugo, J. A., Thorwald, M. A., Cacciottolo, M., D’Agostino, C., Chakhoyan, A., Sioutas, C., Tanzi, R. E., Rynearson, K. D., & Finch, C. E. (2024). Air pollution amyloidogenesis is attenuated by the gamma-secretase modulator GSM-15606. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 20(9), 6107–6114. https://doi.org/10.1002/alz.14086