In the last few articles we have discussed how short term stressors (acute, slightly stressful events) such as heat and cold exposure activate hard encoded genetic pathways to activate repair mechanisms and improve the net resilience of the body.
Endorphins are the feel good hormones that most people have heard about, and that keep runners heading out to the trails for their daily healthy high! Dynorphins are the bad cousins of endorphins - and cause you to feel the opposite - not good! Dynorphins are activated by heat stress and help to cool the body down, but in the process they make a person feel uncomfortable and dysphoric. They bind to kappa opioid receptors and are an important part of the thermoregulatory pathway. A big reason why short term exposure to extreme temperatures helps overall wellbeing is that activation of the dynorphins changes the way your brain responds to the feel good endorphins.
Endorphins bind to opioid receptors called mu-opioid receptors. Activation of dynorphins results in more receptors being made on the mu-opioid receptors and also makes them more sensitive to endorphins. The result is that the next time you make endorphins after doing something very pleasurable such as exercise or hugging, you feel so much better because the endorphin effects are stronger and last longer. This contributes to improved overall well being.
Now to introduce heat shock proteins or HSPs which play an important role inside our cells. They ensure proteins maintain their 3D structure which is essential to the proteins normal functioning. Normal life is constantly damaging proteins with even day to day activities such as breathing and eating all causing problems.
When a protein unfolds, its half life increases and the protein remains inside the cell too long, causing protein aggregates such as the now infamous amyloid beta which plays a role in brain aging and neurodegenerative diseases such as Alzheimer’s. Heat shock proteins help repair protein damage and the unfolding that results from this, and help restore the protein to its correct structure.
FOXO3 is a gene which is a master regulator of many genes which are related to our body’s ability to handle stress. It activates genes to repair damaged protein, DNA and cells. When cells are damaged they become senescent - a state in which they are not really alive or dead. They simply sit there, releasing inflammatory molecules which damage the cells around them and can lead to cancers developing. FOXO3 activates cells that clear away these senescent cells thus preventing further damage and aging.
As with all of our genes, different people have different variants of the same gene. The variant known as FOXO3 is strongly associated with human longevity. This is because this version is active all the time and doesn't wait to be switched on by heat shock. Therefore any damage is constantly being repaired, keeping the person younger and healthier for way longer than people with the standard FOXO3 gene. In fact, those lucky people with this gene variant are almost three times more likely to live until 100!