What doesn’t kill you could actually make you stronger

The phrase “what doesn’t kill you makes you stronger” is one that we have all heard at some point in our lives but Professor Gerald Shadel of the Salk Institute has gone further in proving how this might be true on a cellular level.

Mitochondria are known as the powerhouses of cells – they’re the part of a cell in which respiration takes place, a fundamental process of conversion of food to chemical energy that happens in all living organisms. During respiration, mitochondria form a chemical known as superoxide which is critical for cell function but is toxic to the cell in high concentrations. To prevent build-up of superoxide, the enzyme superoxide dismutase (SOD) is also produced by mitochondria to convert superoxide to a less toxic form.

During respiration, mitochondria form a chemical known as superoxide which is critical for cell function but is toxic to the cell in high concentrations

Using this information and a group of genetically identical mice in utero, Professor Shadel led a team of researchers to investigate how short-term stress by exposure to mitochondrial superoxide very early in development might affect health later on. Half of the mice in the group had a molecular “off” switch for the SOD enzyme, deactivating the enzyme and resulting in brief stress exposure to mitochondrial superoxide.

All the mice grew to adulthood with both halves of the group looking very similar. However, liver samples taken when the mice were four weeks old showed that the group with the molecular “off” switch had higher levels of antioxidants, less superoxide build-up and more mitochondria than the mice not exposed to stress from mitochondrial superoxide. While this in itself was quite surprising, it was supported by cells grown in dishes showing the same results – cells with the SOD switch were healthier from a cellular aspect than the cells without the switch.

Professor Shadel led a team of researchers to investigate how short-term stress by exposure to mitochondrial superoxide very early in development might affect health later on

Genetic analysis of the cells to determine which genes were being activated in both the mice and the cells grown in the lab showed that unexpected molecular pathways in the SOD group were re-programming mitochondria to produce fewer toxic molecules whilst also increasing their antioxidant capability. The work supports the concept known as mitohormesis, where short-term stress results in long-term adaptations in the cell. This can help to ward off ageing by keeping cells healthy for longer and has implications in therapies for disease.

Being able to combat ageing is an exciting field of scientific research with an increasingly better understanding of the genetic information carried in our cells. As such, Professor Shadel aims to take his research further to explore the effects of these pathways in delaying the effects of ageing in mammals. Therefore, this is a promising area of research for future developments in the treatment of age-related diseases such as cancer, Alzheimer’s and cardiovascular disease.