P38 Kinase/NRF2 Pathway May Play Important Role in Behaviors of Advancing Age and Parkinson's, Study Suggests

 

Researchers have made an important discovery in the biology of aging. According to a new study, scientists have found that a gene called P38 is responsible for determining lifespan and conditions related to aging. They found that flies that had an excess of p38 showed a delay in locomotor challenges that occur with aging. The flies that were engineered to lack P38 exhibited behaviors typical of advanced age, according to the report. Both processes involve oxidative stress. The flies lacking P38 showed elevated levels of oxidative stress while the flies that produce extra levels of p 38 exhibited minimal signs of oxidative stress.

Most of the researcher studies have focused on Parkinson's disease. Past studies have found that exposure to certain pesticides produce oxidative stress and can heighten the disease risk of Parkinson's in humans and animals. Vrailis-Mortimer wondered if antioxidants could prevent neuronal deterioration after exposure. What he found was that a cocktail of “superfoods” obtained from grocery store fruits, rich in antioxidants could recover the aging and mobility deficits in flies lacking p38. The cocktail consisted of five different fruits and the other cocktail contained acai berry. Supplementation of either “cocktail” extended their lifespan and increased their mobility almost like that of a normal fly. It also preserved their normal circadian rhythm.

Thus far, antioxidant supplements have demonstrated limited success in treating Parkinson's in experiments. However, Vrailis-Mortimer points out that in addition to dosing, timing may be a factor. She stated, “that most trials have been on patients in advanced stages of Parkinson's and that antioxidants may be less effective at later stages of disease.”

Note: 1) One pathway that p38 works through is the p38/MAPK/NRF2 pathway. Since other studies have demonstrated that antioxidants in berries and fruits are activators of the NRF2 pathway, it is likely that this pathway was activated by these “cocktails” although the determination of this was not a goal of the study. 2) “Mammalian p38 mitogen-activated protein kinases (MAPKs) are activated by a wide range of cellular stresses as well as in response to inflammatory cytokines.”

 

“Come Fly with Me”. Linus Pauling Institute. Digital Digest. Summer/Fall 2023. Pg. 7.

 Ana Cuenda and Simon Rousseau. p38 MAP-Kinases Pathway Regulation, Function and Role in Human Diseases, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. Volume 1773, Issue 8, 2007. Pages 1358-1375,