Papers of the Month
Extramural
By Mali Velasco
Metal mixtures linked with biological aging
Exposure to metals may be a risk factor for aging-related diseases in Native American communities, according to NIEHS-funded researchers.
American Indian communities are disproportionately exposed to elevated levels of metals and have higher rates of aging-related diseases, such as heart disease and stroke. However, connecting metals exposures with aging can be difficult because harmful levels of the contaminants may accumulate in the body decades before disease onset. To capture aging processes before disease develops, scientists used a new class of measures called epigenetic clocks, which integrate chemical modifications to a person’s DNA with machine learning algorithms. The scientists used five different epigenetic clocks that collectively measure health, mortality, and chronological aging to estimate biological aging in participants from 12 tribes from the southwest and the Great Plains.
Exposure to a mixture of metals that are essential for biological function — selenium, zinc, and molybdenum — was associated with lower age acceleration. In contrast, exposure to a mixture of toxic, nonessential metals — tungsten, arsenic, and cadmium — was associated with greater age acceleration. This trend continued when individuals were exposed to both essential and toxic metals in tandem.
In addition, high levels of cadmium and zinc, when studied individually, were associated with increased age acceleration across all five epigenetic clocks.
According to the authors, the findings suggest that exposure to metal mixtures, including nonessential cadmium and essential zinc, may contribute to aging-related disease in Native American populations. Because exposure to toxic metals is preventable, these findings provide an additional strategy to prevent aging-related diseases and premature mortality.
Citation: Boyer K, Domingo-Relloso A, Jiang E, Haack K, Goessler W, Zhang Y, Umans JG, Belsky DW, Cole SA, Navas-Acien A, Kupsco A. 2023. Metal mixtures and DNA methylation measures of biological aging in American Indian populations. Environ Int 178:108064.
Antimicrobial chemical may impact the function of immune cells
Cetylpyridinium chloride (CPC), an antimicrobial chemical, inhibits the function of immune system mast cells, an NIEHS-funded study found. Mast cells are found in connective tissue in most of the body’s organs that play a protective role against pathogens and inflammation.
CPC is used in janitorial cleaning products, food disinfection agents, and in personal care products, such as mouthwash and deodorant. Although the antibacterial benefits of CPC are well known, minimal information exists about its potential toxicity.
The researchers treated rat mast cells that are functionally and structurally similar to human mast cells with CPC for one hour. They found CPC suppressed mast cell degranulation — a process that allows the cells to release protective anti-inflammatory molecules in response to injury or infection — even at doses 3,000-fold lower than concentrations in consumer products.
The team further investigated the effects of CPC on calcium because calcium signaling, whereby calcium ions communicate and drive cellular processes, is essential for degranulation. They found that CPC blocked the release of calcium stored in the cell’s endoplasmic reticulum, a network of tubules that serves as the cell’s transportation system. This inhibited calcium uptake into the mitochondria and its flow through plasma membrane channels, which are required for sustaining the calcium levels needed for mast cell degranulation.
These findings show that CPC can be toxic to an organism’s immune system, according to the authors. Additional research is needed to reveal the effects of CPC on other cells that utilize calcium signaling.
Citation: Obeng B, Potts CM, West BE, Burnell JE, Fleming PJ, Shim JK, Kinney MS, Ledue EL, Sangroula S, Baez Vazquez AY, Gosse JA. 2023. Pharmaceutical agent cetylpyridinium chloride inhibits immune mast cell function by interfering with calcium mobilization. Food Chem Toxicol 179:113980.
Mobile air pollution monitoring following an environmental disaster
Nontargeted mobile monitoring can complement stationary monitoring during disaster response to better characterize exposures to air pollution, according to a study funded by NIEHS. In contrast to traditional stationary screening methods that target specific chemicals, nontargeted analysis quantifies all chemicals in a sample and uses large chemical databases to identify unknown components.
In response to a train derailment in East Palestine, Ohio, researchers deployed a mobile air quality monitoring laboratory. The van — containing instrumentation for real-time, highly sensitive air quality analysis — was driven around locations upwind and downwind of the train derailment site for two days.
The researchers found that levels of the air pollutants benzene, toluene, xylene, and vinyl chloride were similar to targeted stationary monitoring data. However, nontargeted analysis revealed numerous other chemicals with increased levels that were missed by targeted screenings, such as formamide and methyl formate, which have been linked to harmful respiratory effects.
Mobile monitoring also showed substantial spatial and temporal variation of the pollutant acrolein that could not be characterized through stationary sampling. Acrolein is a respiratory irritant that enters the air from the burning of fossil fuels and has been linked to cancer in laboratory studies.
According to the authors, nontargeted mobile monitoring offers a more complete picture of how disasters affect air quality and can facilitate efforts to protect public health.
Citation: Oladeji O, Saitas M, Mustapha T, Johnson NM, Chiu WA, Rusyn I, Robinson AL, Presto AA. 2023. Air pollutant patterns and human health risk following the East Palestine, Ohio, train derailment. Environ Sci Technol Lett 10(8):680-685.
Dogs and horses may be important indicators of PFAS exposure
Companion animals and livestock may provide insight into human exposure to PFAS inside and outside the home, according to an NIEHS-funded study. The scientists identified elevated levels of PFAS in dogs and horses from Gray’s Creek, North Carolina — a neighborhood near a PFAS manufacturing plant.
The team recruited participants with well water PFAS contamination after community members raised concerns about the health of their pets. They collected blood samples from the participants’ animals — 31 dogs and 32 horses — to test for 33 types of PFAS.
Researchers detected PFAS in all animals, and at least 12 types of PFAS in more than half of the dogs and horses. The types of PFAS and concentrations of the chemicals differed between animals. For example, dogs that drank bottled water provided by their owners had higher levels of PFAS from indoor sources, such as paint and consumer products. Horses that lived outdoors and dogs that drank well water had higher levels of the PFAS compounds produced at the nearby plant.
Concentrations of two types of PFAS found in dogs were similar to the concentrations found in children from another North Carolina town, downstream of the PFAS manufacturing plant. The researchers also found changes in key proteins in the animals’ blood related to kidney and liver function. These organs are known to be primary targets of PFAS toxicity in humans.
According to the authors, these findings suggest that dogs and horses may provide critical information about routes of exposure and potential PFAS toxicity, particularly during sensitive developmental windows, such as childhood.
Citation: Rock KD, Polera ME, Guillette TC, Starnes HM, Dean K, Watters M, Stevens-Stewart D, Belcher SM. 2023. Domestic dogs and horses as sentinels of per- and polyfluoroalkyl substance exposure and associated health biomarkers in Gray’s Creek North Carolina. Environ Sci Technol 57(26):9567-9579.
(Mali Velasco is a research and communication specialist for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)
