What factors determine if you will experience healthy and cheerful aging or if it will turn into an endless chain of suffering from numerous health conditions?
Many factors shape our health, including genetics, diet, physical activity, smoking and stress. Some other factors may be as powerful but may not yet be recognized.
I am an environmental toxicologist studying how man-made chemicals affect our health. I was always interested in understanding how our current health is shaped by chemical exposures during the embryonic and early postnatal period – life stages that are particularly sensitive to environmental stressors.
To address these questions, I focused on the analysis of long-term health effects induced by a family of chemicals used as flame retardants called polybrominated diphenyl ethers (PBDEs). The first patent for PBDE use as a flame retardant was issued in 1960, and manufacturing of commercial products containing PBDEs, such as building materials, electronics, furnishings, motor vehicles, plastics, polyurethane foams, baby pajamas and others, began in 1965. PBDEs were first detected by scientists in animal tissues in the 1980s.
Later studies showed that concentrations of these chemicals in human blood, milk and tissues were increasing exponentially over the past 30 years, doubling every five years, while their health effects were poorly understood.
Early exposures trigger lifelong changes in blood lipids
In one of my experiments, I fed mice one of the PBDEs most often found in human blood and milk – BDE-47. The female mice received it from day 8 of their pregnancy until the end of nursing (postpartum day 21).
We exposed mice to 0.2 milligrams of this chemical per kilogram of body weight. This caused BDE-47 concentrations in the fat of experimental animals to reach similar levels to concentrations found in humans living in big American cities. This comparison is used in toxicology to ensure that laboratory experiments use doses relevant for human exposures.
We were surprised to find that triglyceride levels were significantly altered in the offspring of exposed mothers, even though exposure to BDE-47 ceased three months earlier. Triglycerides are main constituents of body fat and cell membranes in humans and other animals.
To understand how BDE-47 changes blood triglycerides and other lipids, my laboratory conducted another experiment with mice. Lipids are insoluble molecules that are used to store energy and as structural components of cell membranes.
We hypothesized that changes in blood lipids result from changes in liver function. It is well-known that the liver regulates composition of lipids in blood. The liver can synthesize new lipids, destroy them, secrete lipids to blood and absorb them from blood.
To test our hypothesis, we exposed female mice to BDE-47 daily during pregnancy or during the period of lactation and analyzed health outcomes in offspring when they reached one year old – roughly equivalent to 50 years in humans.
This experiment again demonstrated that short-term exposure to BDE-47 during early steps of development results in long-lasting effects on blood lipids in mice. These effects were very similar in animals that were exposed during the embryonic period or during nursing.
Reprogramming the balance of lipid in blood and liver
In exposed animals, levels of blood triglycerides fell by half, and livers accumulated 20 percent to 40 percent more lipids than in mice that were never exposed to the chemical. Activity of many liver genes encoding enzymes important for lipid metabolism was altered in exposed mice.