How scientists are utilizing body's positive response to small doses of stress

Every day, the cells in our bodies encounter conditions that can potentially impair their function, damage their structures or even cause them to die. At the same time, cells have sophisticated defence mechanisms that allow them to respond to these threats. Intriguingly, exposing cells to relatively small amounts of stress can sometimes strengthen those defences, a process known as hormesis. Scientists are now examining whether certain substances in food, as well as medicines, could be used to activate these natural protective mechanisms and potentially improve health.

One particularly well-studied system involves NRF2, a protein that functions as a kind of molecular control switch for hundreds of protective genes. Once activated, these genes can help cells reduce damage and eliminate potentially harmful substances, as an article published by The Conversation outlet on this topic recalls.

As the piece lays out, cells encounter a wide range of potentially damaging influences throughout their lives. These include ultraviolet radiation from sunlight, alcohol, environmental pollutants and chemical byproducts produced by some medicines.

Such exposures can harm DNA, the molecule that contains a cell’s genetic instructions, as well as proteins and the fatty membranes that surround cells. When this damage exceeds a cell’s ability to cope with it, normal cellular functions can be disrupted and the cell may eventually die.

Despite being exposed to these threats on a continual basis, most cells are remarkably capable of maintaining their functions over the course of a lifetime. They do this through specialised systems that recognise different forms of stress and respond by changing the activity of genes involved in cellular protection.

Other cellular defence mechanisms perform different tasks, including breaking down and recycling damaged proteins, repairing DNA and temporarily slowing cell division. These responses can help conserve resources and prevent cellular damage from becoming more extensive.

In some circumstances, however, these systems appear to do more than simply respond to damage. A relatively minor stress can trigger an adaptation that subsequently makes a cell more capable of dealing with a stronger challenge. This biological phenomenon, in which a small dose of stress can produce a beneficial response, is known as hormesis.

A useful comparison can be made with the way muscles respond to physical exercise. Temporary strain followed by recovery prompts muscles to adapt, allowing them to cope more effectively with subsequent demands. Some cellular defence mechanisms may operate on a comparable principle: a limited challenge can stimulate changes that leave cells better equipped to withstand another stress later.

Controlled triggering of stress response

Scientists have suggested that this mechanism may partly explain how the body responds to certain chemicals naturally produced by plants. Plants make many of these compounds as defences against insects and other predators. When people consume fruits, vegetables and other plant foods, some of these substances may produce a relatively mild stress signal in cells, potentially prompting their protective systems to become more active.

Cruciferous vegetables such as broccoli offer one example. Cutting or chewing these vegetables leads to the formation of sulforaphane, a compound that has been shown to activate the NRF2 pathway in laboratory-grown cells and in animals.

As the article points out, however, it remains unclear whether eating broccoli or consuming sulforaphane produces the same NRF2 response in humans. Researchers have faced a particular challenge in finding reliable ways to detect changes in cellular stress responses using a simple blood sample. Identifying suitable biomarkers could make it easier to study sulforaphane and similar compounds in people and determine whether their effects translate into meaningful health benefits.

The study of how cells detect and respond to stress has been underway for decades. A better understanding of these mechanisms could have applications extending well beyond nutrition. Researchers are increasingly exploring whether deliberately activating cellular defence pathways could form the basis of treatments for certain diseases.

Omaveloxolone is one example of this approach. The medicine activates NRF2 and, in April 2025, became the first drug specifically approved in the UK for Friedreich’s ataxia, a rare inherited disorder that progressively affects the nervous system and can impair movement. In a 48-week clinical trial, participants who received omaveloxolone performed better on a measure of physical impairment than those who received a placebo.

Nevertheless, activating the body's stress-response systems is not necessarily beneficial in every circumstance. As the article notes, excessive or prolonged activation could itself have undesirable effects. Researchers therefore still need to determine which cellular pathways can be safely manipulated, how strongly they should be activated and which diseases are most likely to respond to this approach.

By Nazrin Sadigova