Chinese scientists have discovered key metabolites for anti-aging

◎ Science and Technology Daily reporter Zhang Jiaxing

When the Year of the Tiger arrives, everyone is talking about tigers, and today we talk about tiger food - deer.

Deer antler velvet on deer is the only mammalian organ found to be fully regenerative.

Over the years, deer antler velvet has been medicated, or as a dietary supplement, and people hope to gain anti-aging and disease prevention capabilities from it, but the mechanism is not well understood.

On February 1, a study by mainland scientists was published in Cell Discovery, which looked for what kind of life active substances make deer antler velvet have the ability to regenerate by mapping a variety of cells, including deer antler stem cells.

Screenshot of the paper

"Our analysis included deer antler stem cells, as well as buds from the 'King of Regeneration' salamander severed limb regeneration, young primate tissues, and human stem cells with strong regenerative abilities." Qu Jing, one of the corresponding authors of the paper and a researcher at the Institute of Zoology of the Chinese Academy of Sciences, introduced, "After analyzing these cells with high precision, we hope to find out what different components are in them that lead to differences in regenerative ability."

Stem cells "get older and more useless"

Or is it "the more evolved the less useful it is"?

During the annual antler regeneration process, deer antler stem cells located in the periosteum of the antler can differentiate to produce intact antler organs including blood vessels, cartilage, bone, dermis and nerves. It can be seen that stem cells are the "protagonists" of regeneration.

"The regenerative and repair effects of stem cells are cross-species, and human adult stem cells can also regenerate and repair a variety of tissues and organs." Qu Jing said, but the problem is that this ability continues to weaken with aging.

One clue scientists have identified is that both evolution and aging have reduced this coveted regenerative capacity. It is speculated that it is possible that the same changes have occurred in aging and evolution.

The team decided to use the law of stem cells "the older the more useless", compared with "the more evolutionary regeneration is more difficult", to learn from the regeneration process of inferior animals that exist in nature, to learn from young stem cells with strong regenerative ability, and to reveal the regenerative superpower.

Pro-regenerative, anti-aging

Key active substances surface

"We chose the metabolic level for analysis." Qu Jing said that there have been previous analysis studies at the gene level and transcriptome level, although the metabolic level is more complex and cumbersome, but the reflection on living organisms is more direct, and there is less confusing information. What's more, evolutionarily conserved small molecule metabolites do not have interspecies-to-species immune rejection.

With the development of biotechnology, the means of capturing small molecules of metabolism are constantly improving. Cyclic metabolism of tricarboxylic acid, pentose phosphate metabolism, glycogen anabolic metabolism, polyamine metabolism, uracil metabolism, fatty acid metabolism... The roadmap of metabolic pathways has been constantly "circled" over the years.

Within the framework of the existing metabolic pathways, the research team analyzed a large number of cells across species, ages, and tissues, and found that regenerative cells have their own "preferences" for metabolic pathways, and enrichment of polyamine metabolism, uracil metabolism, fatty acid metabolism and so on occur more frequently.

"We believe that these metabolic pathways are cross-species conservative, closely related to regeneration, and may contain the code for regeneration." Zhang Weiqi, one of the corresponding authors of the paper and a researcher at the Beijing Institute of Genomics of the Chinese Academy of Sciences, said.

At the same time, the research team combined with the existing human stem cell aging research platform to conduct a meticulous screening of potential regenerative metabolites, and finally found a "star molecule" uridine.

According to the data, uridine has previously been used as a drug to prevent and treat cardiovascular and cerebrovascular diseases.

In the latest paper, researchers have proved through animal experiments that urinary glycoside treatment in mice by injection, application, oral administration and other means can promote the repair of 5 tissues and organs after damage. For example, mice with muscle damage enhanced limb grip, mice with hair damage achieved hair regeneration, mice with myocardial infarction had enhanced heart contractility, and mice had liver fibrosis alleviated... Feeding uridine directly to elderly mice for two months also significantly increased their systemic motor capacity. These studies confirm that uridine is a key metabolite that can delay the aging of human stem cells and promote the regeneration and repair of mammalian multi-tissue.

"We believe that the single metabolite uridine can promote the regenerative repair process of mammalian multi-organ tissues." Zhang Weiqi explained, and the higher uridine content in the blood of young people compared with the blood of the elderly also proves this.

According to reports, the research has been funded by the Ministry of Science and Technology, the National Natural Science Foundation of China, the Chinese Academy of Sciences and the Beijing MunicipalIty. Liu Guanghui, researcher of the Institute of Zoology of the Chinese Academy of Sciences, Qu Jing, researcher of the Institute of Zoology of the Chinese Academy of Sciences, and Zhang Weiqi, researcher of the Beijing Institute of Genomics of the Chinese Academy of Sciences, are the co-corresponding authors of the paper.

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Source: Science and Technology Daily

Editor: Liu Yiyang

Review: Wang Xiaolong

Final Judge: He Yi