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This article on dietary restrictions is part of a long series covering all things related to aging and longevity. Other articles in the series touch on cellular aging, bone and muscle maintenance, heart health, DNA damage, and many other topics.
There is a saying that goes, “You are what you eat.”But how many Eating may be just as important. In recent years, dietary restriction has been shown to extend lifespan and improve health, at least in mice and fruit flies. Dietary restriction is also associated with slowing brain aging and delaying the onset of cognitive decline. However, the exact mechanism by which this is done remains unclear. Researchers at the Buck Institute on Aging may have solved a key part of this mystery. Their discovery is nature communicationssuggests that the brain benefits associated with dietary restriction can be traced to a gene called . Oxidation resistance 1 (OXR1)helps protect cells from oxidative damage.
Discovery of longevity genes
Drosophila melanogaster has a short lifespan of 40 to 50 days, making it ideal for longevity research. Researchers can quickly observe the effects of environmental and genetic factors, such as diet, on aging and lifespan. To facilitate this research, scientists developed the Drosophila Genetic Reference Panel (DGRP), a collection of approximately 200 “standardized” Drosophila strains.
In this study, the Buck Institute team utilized 160 strains from a reference panel. He divided each strain into two groups. One group is where you can eat as much as you want; freely To put it in technical terms, some people were eating only a tenth of what they normally eat. After the fruit fly had gone through its complete life cycle, its genome was scanned.
The researchers focused on five gene variants that were strongly correlated with extreme longevity. Two of the genes are known to have corresponding versions in humans. Ferredoxin (Fdxh) and Mustard (MTD). The human versions of these genes are: Ferredoxin 2 and Oxidation resistance 1 (OXR1)), Each. They evolved from a common ancestor in the distant past and likely continue to perform similar functions across species.
these, Mustard/OXR1 attracted the attention of researchers. The missing person is Oxidation resistance 1 This gene has severe defects in the central nervous system and brain. They also tend to die early. On the other hand, in mouse models, artificial overactivation of this gene can lead to amyotrophic lateral sclerosis (ALS), a disease that affects motor neurons in the spinal cord and causes progressive muscle weakness and destruction. protect from
OXR1 and brain health
Depending on the situation, genes can be turned “on” or “off.”This process is known as gene expression, determines when and where proteins and messenger RNA (mRNA) are made. After all, genes provide the genetic instructions for protein production. Regulation of gene expression also functions as a type of “quantity control” by determining the amount of protein produced. When genes are highly expressed in the “on” position, they are said to be upregulated or overexpressed. When their expression is reduced, or in the “off” position, they are downregulated or underexpressed.
Analysis of the Drosophila genome showed that dietary restriction resulted in a seven-fold increase in expression in fruit flies. mustard mRNA in the Drosophila brain. These were the same fruit flies that showed increased lifespan.block the expression of mustard The gene, on the other hand, caused severe developmental defects and shortened lifespans, regardless of the diet the mice ate.This suggests that mustard Essential for longevity.
Similar results were observed when analyzing expression in human neurons. Oxidation resistance 1 And lifespan.
But how is that? Mustard/oxidation resistance 1 Do genes influence longevity and brain health? Researchers found that it may be due to a process known as endosomal protein recycling. Simply put, this is a kind of cellular waste management system. Once things enter the cell, they need to be sorted and separated into a “garbage” pile to be destroyed and a “recycle” pile to be destroyed. It is returned to the cell membrane and recycled.
A key player in endosomal recycling is a multi-protein complex called retromer. This protein complex is conserved across all eukaryotes, essentially all animals, plants, and fungi. Malfunction of retromer causes abnormalities in lysosomes, which are the “incineration machines” of cells, which prevents the removal of cellular debris and causes garbage to accumulate. Mutations in retromer are associated with Alzheimer's and Parkinson's diseases.
Through genetic analysis and experiments, researchers came to the following conclusions: Mustard/oxidation resistance 1 It interacts with and maintains the retromer complex and helps prevent neurodegenerative complications associated with its dysfunction. This is confirmed by the fact that artificially stabilizing the retromer complex can somehow rescue the underlying cognitive and longevity impairments. Mustard/oxidation resistance 1 deficiency. Dietary restriction promotes brain health by increasing the expression of these genes.
Notes
Although this work is exciting, there are some caveats. These are the same caveats that much of the research on dietary restriction faces.
The first thing to consider is that fruit flies are very different from us humans. That's exactly why it's such a useful resource for studying longevity. They are small, relatively simple, and short-lived. We are relatively large, complex, and long-lived. This makes it difficult to apply conclusions from Drosophila studies to humans. The same goes for studies in mice. In fact, animal research as a whole does not always predict human outcomes well. The closer the animal is to humans, the more transmissible the results will be. Consider research on apes and monkeys. However, the closer an animal is to humans, the longer its natural lifespan, making longevity difficult to study.
Another problem with many of these studies, including those discussed here, is at the methodological level. Animals that are not on a restricted diet can often eat whatever they want. Consider the Latin term used above. freely Or “Look forward to it.” This risks skewing the results, as there are differences in lifespan between diet and non-diet groups. freely Groups that are allowed to binge drink may have worse overall health.
More broadly, testing the effects of dietary restriction in humans is difficult. Again, we live long lives, so it will take a while to see results. Still, there are many factors that influence longevity, so it's difficult to pinpoint just one. Finally, it is unlikely that humans will be able to maintain the same standards of caloric restriction as other animals. Good luck if you can convince him to eat only 10% of his normal intake for most of his life.
Meaning and points
Even though the results of this latest study should be taken with a grain of salt, they do provide valuable insight into the mechanisms that may regulate brain health and aging. According to researchers, dietary restriction increases the occurrence of the following symptoms: Mustard/oxidation resistance 1 These genes help maintain retromer function in neurons. This prevents cognitive decline and reduces the risk of neurodegenerative diseases.
This information could be useful in the development of active drugs in the future. Oxidation resistance 1 It occurs independently of caloric intake. By cutting out the middleman, you get all the benefits of restrictive dieting and none of the frustrations.
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