New Breakthrough: Controlling Free Radicals to Fight Aging and Disease

In 1956, Denham Harman suggested that aging results from the accumulation of oxidative damage in cells, and this damage is caused by free radicals generated during aerobic respiration. [1]. Free radicals are uunstable atomsWhich has unpaired electrons, which means that free radicals are constantly looking for atoms that have electrons that can come in to fill space. This makes them very reactive, and when they steal atoms from your cells, it’s very dangerous.

Longevity Technology: Apart from being generated in the normal metabolism of cells, free radicals can be obtained from external sources (pollution, cigarette smoke, radiation, drugs, etc.) While the theory of aging free radicals have been widely debated [2]Understanding the dangers posed by free radicals is increasing public interest in superfoods, vitamins, and minerals that are antioxidants—substances with spare electrons that they are happy to provide to bypass free radicals, thereby removing them from the harmful equation.

But before you get to blueberries, it’s important to recognize that the story, as is so often the case in biology, is not black and white. Like misunderstood cartoon villains, free radicals also have a beneficial side – though not to excess. Free radicals generated by the mitochondria of cells are useful in wound healing, and others act as important signaling agents. Free radicals are used as weapons by the body’s defense system, destroying disease-causing microbes that attack to prevent disease.

Cells need a certain level of basic control of free radicals as they signal molecules, activating protective pathways. So if they are all doused with antioxidants, the role of natural, protective and homeostatic radicals in cells is also eliminated.

The yin-and-yang nature of free radicals is why smoothing them is key—and now researchers at the Buck Institute for Aging Research and Calico Laboratories have found a new way to deal with them: Instead of washing them down with antioxidants, take a pill that selectively prevents them from being produced. beginning. .

Researchers have found that they can specifically block the production of free radicals in the mitochondria, the powerhouses of our cells, which, when they become dysfunctional due to age or damage, begin to decrease the cell’s energy production and increase free radical production.

Posted in Free Radical Biology and MedicineIn this study, the researchers demonstrated that specifically inhibiting free radical production at certain mitochondrial sites prevented and treated the metabolic syndrome in mice by preventing and reversing insulin dependence. [3].

“We believe that mitochondrial radical production causes many chronic aging diseases, and blocking free radical production is an effective disease-fighting and anti-aging treatment,” said Martin Brand, PhD, Buck Professor Emeritus and principal investigator on the study. .

Martin Brand, Ph.D., Professor Emeritus Buck and senior investigator of the study

“We have found a way to selectively control problematic free radicals without compromising normal energy production in mitochondria. This compound acts like a cork in a wine bottle. They clog specific sites so that free radicals are not produced, without hindering mitochondrial critical functions in energy metabolism. We look forward to continuing this pioneering research area.”

The developed bioavailability compound, S1QEL1.719 (“New S1QEL” – IQ Electron Leakage Site Blocker), is administered preventively and therapeutically to rats fed a high-fat diet that causes metabolic syndrome. Treatment reduces fat accumulation, strongly protects against decreased glucose tolerance and prevents or reverses increased fasting insulin levels by protecting against the development of insulin resistance.

Today, Mitochondrial Complex I; Tomorrow world

S1QEL1 acts on IQ in situ at mitochondrial complex I (The mitochondrial electron transport chain consists of four protein complexes embedded in the inner mitochondrial membrane. Together, they carry out a multistep process by which the cell obtains 90% of its energy.)

The current literature strongly implicates compound I in a number of different diseases, from metabolic syndrome to Alzheimer’s disease, fatty liver disease, and noise-induced hearing loss, as well as the underlying aging process itself, said first author and Buck team scientist Mark Watson, Ph.D. .

Mark Watson, PhD, senior author and PAC team scientist

“S1QEL does not scavenge oxidants or radicals. Rather, they specifically inhibit radical production at the IQ site in complex I without interfering with other sites,” said Watson. “So the normal redox signaling that we need in our cells will continue. S1QEL just modified that site. They are very clean, very specific, and don’t disrupt mitochondria the way mitochondrial blockers do.”

Brand says data shows that free radical production of compound 1 is a major driver of insulin resistance and metabolic syndrome, major diseases associated with poor lifestyle choices and aging. He said this feature is a compelling reason to reconsider the mitochondrial theory of aging.

“These compounds regulate the production of mitochondrial free radicals,” he said. “And this is very interesting; simply inhibiting this specific site improves the entire redox environment and prevents metabolic disease, which is amazing.”

[1] https://escholarship.org/content/qt3w86c4g7/qt3w86c4g7.pdf
[2] https://www.sciencedirect.com/science/article/abs/pii/S0531556505002032
[3]

Featured image: Julee Ashmead/Vecteezy.
Additional image: Buck Institute for Research on Aging

2023-07-14 03:37:12
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