As climate change continues to impact our world, one growing concern is the effect of extreme heat events, especially on vulnerable populations like the elderly. A new study published in the journal Scientific Reports has delved into the complex ways that periodic heat waves can impact the vital organs of older individuals.
Scientists at the University of California-Irvine (UC Irvine) used cutting-edge genetic sequencing techniques to examine how heat stress alters gene activity in the brains and livers of aged mice. What they discovered was a web of interconnected effects involving the gut, liver, and brain.
The study found extreme heat triggers inflammation in the gut, throwing off the balance of healthy bacteria that normally reside there. This gut imbalance, known as dysbiosis, sends signals to the liver that ramp up production of a protein called orosomucoid 2, or ORM2.
“Inflammation in the brain and spine contributes to cognitive decline, compromises the ability to form new neurons and exacerbates age-related diseases,” says corresponding study author Saurabh Chatterjee, a professor of environmental & occupational health at the UC Irvine Program in Public Health. “By investigating the effects of heat stress on the gut-liver-brain crosstalk, we can better protect our increasingly vulnerable aging population.”
While ORM2 is thought to play a role in regulating fat metabolism in the liver, researchers found that too much of it can escape the liver and make its way to the brain. Normally, the blood-brain barrier acts as a strict gatekeeper, preventing unwanted substances from entering the brain. But the heat stress seems to make this barrier leaky, allowing the ORM2 to sneak through.
Once inside the brain, the excess ORM2 appears to wreak havoc, triggering inflammation and impairing the function of neurons involved in learning and memory. UC Irvine researchers observed increased activity of immune cells in the brain called microglia, which can further exacerbate neuroinflammation when overactivated.
At the same time, the team noted decreased levels of a protein called BDNF that is crucial for maintaining the health and adaptability of brain cells. Lower BDNF is associated with impaired cognitive function and has been implicated in conditions like Alzheimer’s disease.
But the story doesn’t end there. Researchers also found distinct changes in gene activity patterns in both the brain and liver tissues of the heat-stressed mice. In the brain, they observed increased activity of genes involved in inflammation and decreased activity of genes that help protect neurons from damage.
In the liver, heat stress ramped up genes involved in immune responses and liver injury. It also dialed down the activity of genes related to the body’s internal clock and healthy fat metabolism. These liver-specific changes may further exacerbate the harmful effects on the brain by contributing to system-wide inflammation.
The study paints a picture of a vicious cycle, where heat stress triggers a cascade of damaging effects that bounce between the gut, liver, and brain. Researchers believe this may help explain why older individuals are particularly vulnerable to the health impacts of extreme heat.
While the study was conducted in mice, the genetic similarities between mice and humans mean the findings likely apply to us as well. UC Irvine researchers hope that by shedding light on the underlying molecular mechanisms, their work can pave the way for new strategies to protect the elderly from the dangerous health consequences of heat waves.
“Our findings have the potential to be used for the development of prognostic and therapeutic markers for precise interventions,” concludes Chatterjee. “In a dynamically changing global landscape, the imminent threat of climate change is evident in rising temperatures, raising concerns about intermittent heat waves. Our heating planet is undoubtedly leading to acute and chronic heat stress that harms the health of our aging population.”
