Science sub-journal: fill in important gaps!

Where do we come from? who are we? Where are we going?

Where do we come from? who are we? Where are we going?

We go to old age, to death
.

We go to old age, to death
.

Aging is the inevitable end of most living things
.

The research on aging, "why aging" and "can we stay old" are one of the most profound and fascinating studies in the history of science

Aging is the inevitable end of most living things

In the study of aging, dozens of theories have been put forward, some of which have become history, and some are still shining, such as genetics, telomere, free radicals, nutrition, etc.

Legend: Nine markers of aging: genomic instability, telomere attrition, epigenetic alterations, loss of protein homeostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication in stem cells

And a recent study has made waves in this field again, and the "error catastrophe theory", which has been silent for a long time, has once again attracted people's attention
.

And a recent study has made waves in this field again, and the "error catastrophe theory", which has been silent for a long time, has once again attracted people's attention
.

The "error catastrophe theory" was put forward by chemist Leslie Orgel in 1963.
He believed that the cause of aging lies in RNA translation errors, leading to the synthesis of defective proteins, more and more wrong proteins, destroying normal physiological functions, and eventually cause aging
.

The "error catastrophe theory" was put forward by chemist Leslie Orgel in 1963.
He believed that the cause of aging lies in RNA translation errors, leading to the synthesis of defective proteins, more and more wrong proteins, destroying normal physiological functions, and eventually cause aging
.

There was not enough research evidence to support this theory at the time, and in recent years there has been some evidence that the accumulation of faulty proteins can accelerate aging, including:

There was not enough research evidence to support this theory at the time, and in recent years there has been some evidence that the accumulation of faulty proteins can accelerate aging, including:

Compared with the long-lived star in rodents and the African naked mole rat with a lifespan of up to 30 years, compared with the laboratory mouse Siwuqi, which can only live for 2-3 years, there are fewer wrongly synthesized proteins in the body;

Compared with the long-lived star in rodents and the African naked mole rat with a lifespan of up to 30 years, compared with the laboratory mouse Siwuqi, which can only live for 2-3 years, there are fewer wrongly synthesized proteins in the body;

Yeast, fruit flies and nematodes were genetically modified to increase the accuracy of protein synthesis, and they lived 23 percent longer
.

Yeast, fruit flies and nematodes were genetically modified to increase the accuracy of protein synthesis, and they lived 23 percent longer
.

A recent study by Erik Böttger and colleagues from the University of Zurich in Switzerland has demonstrated for the first time that incorrect protein synthesis can lead to shortened lifespan and accelerated aging in mammals
.

The study was published March 2 in Science Advances

A recent study by Erik Böttger and colleagues from the University of Zurich in Switzerland has demonstrated for the first time that incorrect protein synthesis can lead to shortened lifespan and accelerated aging in mammals

"This study fills a critical gap that we can finally be sure of: missynthesized proteins are accelerators of aging,

To test whether "mistakes in protein synthesis" contribute to aging in mammals, the researchers genetically engineered mice to generate Rps9 D95N heterozygous knock-in mice, which have error-prone ribosomes that are More erroneous proteins were produced in the process, as exemplified by translation errors that resulted in proteins that were too long, twice as often in Rps9 D95N mice than in normal mice
.

To test whether "mistakes in protein synthesis" contribute to aging in mammals, the researchers genetically engineered mice to generate Rps9 D95N heterozygous knock-in mice, which have error-prone ribosomes that are More erroneous proteins were produced in the process, as exemplified by translation errors that resulted in proteins that were too long, twice as often in Rps9 D95N mice than in normal mice
.

When young, these Rps9 D95N mice were virtually indistinguishable from normal mice and looked remarkably healthy
.

But by 9 months (equivalent to humans in their 30s), the Rps9 D95N mice began to show marked signs of premature aging, including hair loss, graying, hunched backs, and deformed chests

When young, these Rps9 D95N mice were virtually indistinguishable from normal mice and looked remarkably healthy

In terms of body composition, Rps9 D95N mice began to lose weight and decreased subcutaneous and visceral fat content at 9 months, while normal mice did not show weight loss until 18 months and humans after 65 years of age
.

In terms of body composition, Rps9 D95N mice began to lose weight and decreased subcutaneous and visceral fat content at 9 months, while normal mice did not show weight loss until 18 months and humans after 65 years of age
.

In terms of motor function, compared with normal mice, Rps9 D95N mice have slower walking speed, worse swimming ability, and are often sedentary
.

In terms of motor function, compared with normal mice, Rps9 D95N mice have slower walking speed, worse swimming ability, and are often sedentary
.

Not only that, Rps9 D95N mice also showed premature anemia, lymphopenia in the blood, mononucleosis, and extramedullary hematopoiesis in the spleen, all of which are characteristic of mice in the final stages of life
.
Anemia of unknown etiology is also a common symptom in older humans
.

Not only that, Rps9 D95N mice also showed premature anemia, lymphopenia in the blood, mononucleosis, and extramedullary hematopoiesis in the spleen, all of which are characteristic of mice in the final stages of life
.
Anemia of unknown etiology is also a common symptom in older humans
.

Rps9 D95N mice also showed molecular signs of premature aging, producing more free radicals, greater oxidative damage, faster shortening of telomere length, and an epigenetic predisposition to aging than normal mice of the same age.
methylation state
.

Rps9 D95N mice also showed molecular signs of premature aging, producing more free radicals, greater oxidative damage, faster shortening of telomere length, and an epigenetic predisposition to aging than normal mice of the same age.
methylation state
.

More importantly, the risk of premature death in Rps9 D95N mice was 7 times higher than that of ordinary mice.
They began to die at 6.
5 months (around 30 years old), and at 16 months, the rate of death increased , Thus, reducing protein also shortens lifespan
.

More importantly, the risk of premature death in Rps9 D95N mice was 7 times higher than that of ordinary mice.
They began to die at 6.
5 months (around 30 years old), and at 16 months, the rate of death increased , Thus, reducing protein also shortens lifespan
.

Legend: Survival curves of normal mice (grey) and Rps9 D95N mice (pink)

Legend: Survival curves of normal mice (grey) and Rps9 D95N mice (pink)

All in all, this study demonstrates that incorrect protein synthesis can lead to accelerated aging and shortened lifespan, and the next burning question is - how does it contribute to aging? Is wrong protein synthesis related to human diseases of aging?

All in all, this study demonstrates that incorrect protein synthesis can lead to accelerated aging and shortened lifespan, and the next burning question is - how does it contribute to aging? Is wrong protein synthesis related to human diseases of aging?

As the role of protein homeostasis in the aging process is gradually demonstrated, researcher Erik Böttger proposed that "the development of drugs that improve the accuracy of protein synthesis may become a new strategy for preventing
aging" .

As the role of protein homeostasis in the aging process is gradually demonstrated, researcher Erik Böttger proposed that "the development of drugs that improve the accuracy of protein synthesis may become a new strategy for preventing
aging" .
Reference sources for prevention : 1.
Glitchy protein production may hasten aging.
  https:// 2.
Shcherbakov D, Nigri M, Akbergenov R, Brilkova M, Mantovani M, Petit PI, Grimm A, Karol AA, Teo Y, Sanchón AC, Kumar Y, Eckert A, Thiam K, Seebeck P, Wolfer DP, Böttger EC.
Premature aging in mice with error-prone protein synthesis.
Sci Adv.
2022 Mar 4;8(9):eabl9051.
doi: 10.
1126/sciadv.
abl9051.
Epub 2022 Mar 2.
PMID: 35235349.
3.
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G.
The hallmarks of aging.
Cell.
2013 Jun 6;153(6):1194-217.
doi: 10.
1016/j.
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PMID: 23746838; PMCID: PMC3836174.

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