University of Louisville

Using a Toxic Aging Coin Approach to Rethink Drinking Water Safety for Hexavalent Chromium

Grade Level at Time of Presentation

Junior

Major

Neuroscience

Institution 23-24

University of Louisville

Department

1Pediatrics Research Institute, Department of Pediatrics, University of Louisville 2Department of Pharmacology and Toxicology, University of Louisville

Abstract

The U.S. is facing an unprecedented aging crisis. In the next 25 years, 20% of the population will be geriatric (65+) and the centenarian population will reach ~3.6 million. This aging crisis portends an increased prevalence of age-related diseases, emphasizing a need to understand geriatric vulnerability to environmental pollution. The aging crisis is further impacted by environmental pollutants as: 1) geriatrics are more vulnerable to environmental pollutants, and 2) pollutants accelerate biological aging, acting as “gerontogens.” We use a Toxic Aging Coin approach to interrogate the intersection of aging and toxicology; heads examines how age impacts toxicity, while tails examines how chemicals accelerate aging. We propose metals as a class of gerontogens, as they are linked to the 10 most prevalent age-related diseases. Hexavalent chromium (Cr[VI]) is a metal of major concern for environmental and human health, and studies show Cr(VI) may induce age-related diseases. This study explores the heads side to determine how Cr(VI)-induced neurotoxicity is distinct across ages. We exposed young, middle-aged, and geriatric rats (both sexes) to Cr(VI) in drinking water (0.05 or 0.1 ppm) for 90 days. These concentrations reflect maximum permissible drinking water limits set by the WHO and U.S. EPA, respectively. Rats performed a battery of behavioral assays to assess locomotion, anxiety, activity, spatial memory, and sociability. Afterwards, brains were harvested to assess regional metal levels and neuropathology. We observed significantly elevated Cr in the geriatric female hippocampus and slightly elevated levels in middle-aged females, but we found no differences in young females or males of any age. We observed neurodegeneration was higher in the hippocampus than frontal cortex, neuropathology consistent with the behavioral changes we observed. Our data suggest regulatory standards should consider effects in people at all ages and the maximum permissible concentration for Cr(VI) in drinking water should be reassessed.

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Using a Toxic Aging Coin Approach to Rethink Drinking Water Safety for Hexavalent Chromium

The U.S. is facing an unprecedented aging crisis. In the next 25 years, 20% of the population will be geriatric (65+) and the centenarian population will reach ~3.6 million. This aging crisis portends an increased prevalence of age-related diseases, emphasizing a need to understand geriatric vulnerability to environmental pollution. The aging crisis is further impacted by environmental pollutants as: 1) geriatrics are more vulnerable to environmental pollutants, and 2) pollutants accelerate biological aging, acting as “gerontogens.” We use a Toxic Aging Coin approach to interrogate the intersection of aging and toxicology; heads examines how age impacts toxicity, while tails examines how chemicals accelerate aging. We propose metals as a class of gerontogens, as they are linked to the 10 most prevalent age-related diseases. Hexavalent chromium (Cr[VI]) is a metal of major concern for environmental and human health, and studies show Cr(VI) may induce age-related diseases. This study explores the heads side to determine how Cr(VI)-induced neurotoxicity is distinct across ages. We exposed young, middle-aged, and geriatric rats (both sexes) to Cr(VI) in drinking water (0.05 or 0.1 ppm) for 90 days. These concentrations reflect maximum permissible drinking water limits set by the WHO and U.S. EPA, respectively. Rats performed a battery of behavioral assays to assess locomotion, anxiety, activity, spatial memory, and sociability. Afterwards, brains were harvested to assess regional metal levels and neuropathology. We observed significantly elevated Cr in the geriatric female hippocampus and slightly elevated levels in middle-aged females, but we found no differences in young females or males of any age. We observed neurodegeneration was higher in the hippocampus than frontal cortex, neuropathology consistent with the behavioral changes we observed. Our data suggest regulatory standards should consider effects in people at all ages and the maximum permissible concentration for Cr(VI) in drinking water should be reassessed.