Distribution of Mitochondria is Connected to Function in Aging Neurons
Mitochondrial dysfunction is a prominent feature of aging, particularly in tissues with high energy requirements, such as muscles and the brain. Part of the problem is that autophagy to clear out damaged mitochondria becomes less effective. Here researchers show that the distribution of mitochondria in neurons is important to the operation of autophagy and mitochondrial function. Unlike other cells, neurons have very long projections, the axons, that require a sufficiently large population of localized mitochondria for correct function. Aging impairs the mechanisms involved in ensuring that axons are sufficiently supplied with mitochondria, and this in turn impairs function in the brain.
Neuronal aging and neurodegenerative diseases are accompanied by proteostasis collapse, while the cellular factors that trigger it have not been identified. Impaired mitochondrial transport in the axon is another feature of aging and neurodegenerative diseases. Using Drosophila, we found that genetic depletion of axonal mitochondria causes dysregulation of protein degradation. Axons with mitochondrial depletion showed abnormal protein accumulation and autophagic defects. Lowering neuronal ATP levels by blocking glycolysis did not reduce autophagy, suggesting that autophagic defects are associated with mitochondrial distribution.
We found that eIF2β was increased by the depletion of axonal mitochondria via proteome analysis. Phosphorylation of eIF2α, another subunit of eIF2, was lowered, and global translation was suppressed. Neuronal overexpression of eIF2β phenocopied the autophagic defects and neuronal dysfunctions, and lowering eIF2β expression rescued those perturbations caused by depletion of axonal mitochondria. These results indicate the mitochondria-eIF2β axis maintains proteostasis in the axon, of which disruption may underlie the onset and progression of age-related neurodegenerative diseases.
50 years ago I discovered the cause of aging with minimal medical knowledge. I didn't need a double-blind scientific study to do this.
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All I had to do was look at the hands and faces of my grandmother and grandfather, who spent all day in the fields. The parts of their bodies covered by clothing were completely smooth and white like babies.
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And so for 30 years I took drugs that protect against ionizing radiation, the so-called geroprotectors. And now I am 20 years younger than I am.
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I can't understand why in 50 years no one has found the cause of aging, like I have. It even seems to me that they are resisting it, as if they don't want to find it. People also ask me why no one else knows the cause of aging. So why don't these people want to delay aging?. Who knows?
@Dalis : Environmental cause of aging such as solar radiation (ultraviolet rays) is one cause of aging, you are correct. But there are many other causes of aging which are not visible on skin and hair. Breathing oxygen- oxidative stress is another cause of it. Proteins inside the body misfolding and sticking to sugar and fat molecules -- another cause of it. Scientists don't know all the causes yet -- still trying to discover more causes. Then finding treatments to counteract the known causes takes many years. Research is proceeding too slowly. Many people who are waiting for anti-aging pill will be dead before it is approved by governments.
solar radiation (ultraviolet light) is one cause of aging - it makes skin wrinkled and brownish spots on white skin. But there are many other causes of aging ( now it is known seven or nine other causes). scientists are trying to discover more causes ..... Then discovering treatment methods to counteract the known causes takes many years. Many people waiting for anti-aging drugs will be dead before it is discovered and approved for general use.