The anti-aging effects of vitamin C and E are confusing, which may be due to a protein

The researchers said that the study, published in the journal Nature Communications on May 26, showed that future therapies targeting CaMKII can delay senile diseases

The person in charge of the study stated that the evolutionary protection of genes that make young people run faster and respond powerfully to the "fight or flight" response makes sense: it helps them catch prey or avoid predators, thereby ensuring them The reproduction was successful

To further explore oxidative stress and its connection with aging and health, Anderson and his research team genetically engineered mice to make their CaMKII resistant to oxidation

They found that compared with mice with antioxidant CaMKII, mice with oxidized CaMKII were able to run about 150 meters farther on average, which was about 5 meters faster per minute

When the researchers took a biopsy of the muscle tissue of mice and looked for other genes related to muscle growth, exercise recovery, improved blood flow, and immune cell activation (these factors can increase physical endurance), they found that these genes only have Oxidative CaMKII is activated in mice

A one-step experiment showed that CaMKII activity in mouse muscle tissue increased the expression of cell pathways related to inflammation, diabetes, heart enlargement, epilepsy, and obesity

Dr.

The research team at Johns Hopkins School of Medicine also conducted experiments on genetically modified fruit flies to see whether oxidizable CaMKII would have similar performance and health effects in invertebrates, which are not themselves sensitive to oxidation.

The researchers used CRISPR's gene cutting and insertion tools to add oxidation sites to the CaMKII gene in Drosophila DNA

In one experiment, these flies were placed in a glass tube and allowed to climb to the top of the tube

When researchers fed fruit flies with antioxidant food to eliminate the effects of genetically modified CaMKII on oxidative stress, genetically modified flies and non-transgenic flies performed similarly in climbing tests

In another experiment, the researchers fed fruit flies with food containing the herbicide paraquat, which provided the fruit flies with excessive oxidants, which could only activate CaMKII in genetically modified flies, not non-transgenic flies

In contrast, under such oxidative stress, the climbing performance of genetically modified flies carrying oxidizable CaMKII decreased significantly: they were almost 10 millimeters slower than their normal food counterparts, indicating that excessive oxidative stress passed through Oxidation and activation of CaMKII cause the body to decline

Researchers made similar observations on the heart of fruit flies

Wang said the most shocking finding is that although genetically modified flies have better physical performance and heart function, they experience faster age-related decline and die at a younger age

"One of the main effects of evolution is to improve the viability of species, including producing more offspring and being good at finding food

Overall, the researchers say that these findings may provide new targets to address a large number of oxidative damage-related diseases and may also provide an explanation for why research on broad-spectrum antioxidants, such as vitamins C and E, has achieved mixed results.
Treat heart disease, Parkinson's disease and Huntington's disease
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Scientists say that designing a treatment plan specifically for gene regulatory factors such as CaMKII may have a better effect
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"For hundreds of millions of years, these diseases have been programmed into animal genomes, afflicting us in the last moments of our lives," Bever said
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"Obviously, if we want to find treatments, we need to understand their evolutionary roots more fully
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Researchers have found more evidence that CaMKII activates genes related to the early immune response, which is an adaptation of early vertebrates to provide health by helping to fight off infectious diseases
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Scientists have discovered that when people get older, abnormal activation of the immune system can lead to systemic and chronic inflammation and increase the risk of all major age-related diseases
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"CaMKII's ability to activate the immune response in the face of oxidative stress may provide clues to its involvement in aging and disease," Wang said
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Qinchuan Wang, Erick O.
Hernández-Ochoa, Meera C.
Viswanathan, Ian D.
Blum, Danh C.
Do, Jonathan M.
Granger, Kevin R.
Murphy, An-Chi Wei, Susan Aja, Naili Liu, Corina M.
Antonescu , Liliana D.
Florea, C.
Conover Talbot, David Mohr, Kathryn R.
Wagner, Sergi Regot, Richard M.
Lovering, Peisong Gao, Mario A.
Bianchet, Mark N.
Wu, Anthony Cammarato, Martin F.
Schneider, Gabriel S .
Bever, Mark E.
Anderson.
CaMKII oxidation is a critical performance/disease trade-off acquired at the dawn of vertebrate evolution .
Nature Communications , 2021; 12 (1) DOI: 10.
1038/s41467-021-23549-3