A UAB researcher says resilience to warming temperatures starts at the smallest scale. When summers grow hotter and heat waves stretch longer, staying hydrated and watching for signs of heat exhaustion are crucial. While individuals sweat it out on the surface, a silent drama is unfolding inside every one of the trillions of cells that make up the body.
Holly Chen, Ph.D., assistant professor in the University of Alabama at Birmingham Department of Cell, Developmental and Integrative Biology, breaks down how cells sense and respond to heat stress, how they defend themselves, and what their emergency response can teach scientists about aging, cancer and neurodegenerative disease.
What are the cellular effects of heat stress?
Chen compares the body’s cells to a tiny, bustling factory. Under normal conditions, proteins act like workers who know exactly what to do, and the cellular machinery hums along, building new proteins and keeping the factory growing and functioning properly.
As heat increases, that streamlined system begins to break down. The workers, or proteins, get overwhelmed, and the cellular machinery begins to overheat and run less efficiently. If left unchecked, proteins can misfold or clump together, and the cell’s normal operations can grind to a halt or fail entirely.
“To prevent this disaster, the factory immediately switches into ‘emergency mode,’” Chen said. “Instead of focusing on making new products, it temporarily pauses many of its normal activities, such as growth and protein production, and puts all its effort into protecting itself.”
The cell calls in a team of emergency mechanics known as heat shock proteins, whose job is to repair damaged proteins, coax them back into shape and prevent harmful clumping. At the same time, the cell slows down energy-hungry activities and calls upon its cleanup crew, or autophagy, which means “self-eating.”
“Think of autophagy as the factory’s recycling center,” Chen said. “It collects damaged proteins and worn-out machinery, breaks them down into reusable parts, and recycles those materials to keep the factory running until conditions improve.”
Holly Chen, Ph.D. “When cells are under heat stress, they stop worrying about business as usual and focus on what matters most: survival, repair and cleanup.”
How overheated cells sound the alarm
Cells do not have thermometers, but they are remarkably good at picking up on the telltale signs that heat leaves behind. Every protein has a temperature range where it functions best. Once things get too hot, proteins start losing their shape and clumping into harmful aggregates. Cell membranes also become more fluid-like, making it harder for the cell to control what passes in and out.
“These changes are the cell’s equivalent of a fire alarm going off,” Chen said. “They signal that something is wrong, triggering an emergency response to protect the cell before too much damage occurs.”
Damaged cells ignite the body’s repair response
According to Chen, heat can cause proteins to unfold and lose the three-dimensional shape they need to function or stick together into damaging clumps. Heat can interfere with the internal transport structures that move materials around the cell and, in more severe cases, damage DNA itself.
“Fortunately, cells have their own emergency repair crew,” Chen said. “When the damage becomes too extensive to fix through repair alone, cells are left with one last resort.”
Heat shock proteins act like skilled mechanics, helping damaged proteins fold back into their proper shape and preventing them from sticking together. If a protein is too badly damaged to be repaired, the cell tags it for disposal, and autophagy breaks it down and removes it so its building blocks can be reused.
“If the damage becomes too severe for the cell to repair, it may activate a carefully controlled self-destruct program called apoptosis,” Chen said. “This allows the damaged cell to remove itself before it can harm its neighboring cells or the rest of the body. In contrast, if the damage is sudden and overwhelming, the cell may die uncontrollably through necrosis, which can trigger inflammation, and the body’s response to heat.”
Understanding how cellular stress drives disease and shapes new treatments
Cells are under constant stress from heat and factors such as aging, infection, pollution, psychological strain and even poor sleep. Despite how different these sources of stress are, cells tend to respond in remarkably similar ways, relying on the same built-in emergency defense systems to cope. The trouble is that those systems lose efficiency as we age.
“Damaged proteins and other cellular waste can gradually build up, contributing to diseases such as Alzheimer’s and Parkinson’s diseases,” Chen said. “By understanding how the cell’s emergency response team works, we can find new ways to strengthen these natural defense systems and keep our cells healthier for longer.”
Cancer cells present the flip side of the same coin. Cancer cells frequently commandeer these same stress-response systems to survive conditions that would normally be fatal, including low oxygen, nutrient shortages or chemotherapy.
Understanding how cancer cells exploit these protective pathways could point researchers toward treatments that shut down those survival strategies while sparing healthy cells.
Staying informed on heat stress matters now more than ever
“During most hot days, our bodies do an amazing job of keeping our cells at a safe temperature,” Chen said.
But during prolonged or extreme heat waves, that cooling system can be pushed past its limits, especially for older adults, young children, people with chronic conditions like heart disease and anyone taking medication that interferes with temperature regulation. When the body can no longer keep pace, its internal temperature starts to climb, driving cells into heat stress and raising the risk of heat-related illness and organ damage.
“In these situations, heat waves don’t just make us feel uncomfortable; they place extra stress on the trillions of cells that keep our bodies functioning,” Chen said. “By understanding how prolonged heat affects our cells, scientists can better identify who is most vulnerable, develop strategies to protect people during extreme weather, and learn more about how environmental stress contributes to human health and disease.”