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Modern Humans Developed a More Effective Protection Against Oxidative Stress

The ancestral variant of glutathione reductase, a key enzyme that protects against oxidative stress, produces more reactive oxygen than the modern human variant does.

The ancestral form of glutathione reductase, a crucial enzyme that defends against oxidative stress, generates more reactive oxygen than the present human form.

German and Dutch researchers have demonstrated that the ancestral type of glutathione reductase, a crucial enzyme that defends against oxidative stress, creates more reactive oxygen species and raises the cellular amounts of cytokine-encoding genes.

Compared to the comparable proteins in Neanderthals and apes, very few proteins in the body contain a modification that makes them distinct. Researchers at the Max Planck Institute for Evolutionary Anthropology in Germany and the Karolinska Institutet in Sweden have researched glutathione reductase, an anti-oxidative stress protein.

They demonstrate that the risk for inflammatory bowel disease and cardiovascular disease is multiplied several times in Neanderthal variation carriers.

Researchers have struggled for a long time to answer the question of what makes modern people unique. One method to approach this subject is to examine the proteins or building blocks in the body that have undergone alterations carried by practically all living people today and that occurred after our split from our Neanderthal ancestors approximately 500,000 years ago.

Stopping oxidative stress is a bit like preventing something from rusting. Perhaps the fact that we are living longer has driven these changes.

Svante Pääbo

There are around 100 proteins with this specific modification. As part of the body’s fight against oxidative stress, one of these proteins is glutathione reductase.

Hugo Zeberg of Karolinska Institutet & the Max Planck Institute for Evolutionary Anthropology and the coauthor Svante Paabo of the Max Planck Institute for Evolutionary Anthropology led the Science Advances study (Coppo et al., 2022).

ape human oxidative stress

They demonstrate that the Neanderthal protein produced more reactive oxygen radicals, the cause of oxidative stress. It is the third protein variation exclusive to modern humans that has been studied to date.

Approximately 60,000 years ago, when our ancestors interbred with Neanderthals, the study indicates that a little amount of Neanderthal protein was transferred to modern humans. Today, it is prevalent throughout the Indian subcontinent, affecting an estimated 1 to 2 percent of the populace.

The researchers discovered that individuals who inherit the Neanderthal protein are more likely to suffer vascular illness and inflammatory bowel disease, which are connected to oxidative stress.

Hugo Zeberg states, “The risk increases we observe are substantial; the risk of inflammatory bowel disease and cardiovascular disease is multiplied by three.”

The researchers can only hypothesize why this particular mutation is one of the rare mutations that nearly all modern humans possess.

“Preventing oxidative stress is comparable to preventing rusting. Svante Paabo speculates that the fact that we live longer has contributed to these developments.

The Max Planck Society, NOMIS Foundation, the Jeansson Foundations, and the Magnus Bergvall Foundation financed the research. The authors report having no competing interests.

Related Publication and Further Readings

Coppo, L., P. Mishra, et al. (2022). “A substitution in the glutathione reductase lowers electron leakage and inflammation in modern humans.” Sci Adv 8(1): eabm1148.

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