On the day of the Lunar New Year (February 1), a number of Chinese scientists joined hands to present a precious gift for the development of the aging field.
Chinese scholars have conducted research on salamanders and deer antler velvets with super regenerative abilities, and analyzed the metabolic processes of humans and other primates at different ages, and finally found that a substance called uridine can greatly reverse the aging of human stem cells and promote the regeneration of various tissues in the body [1]. 2022 opened the door, and Chinese scientists attacked another city in the study of anti-aging mechanisms.
At the same time, the expert team behind this blockbuster research can be described as "all the stars gathered", including Liu Guanghui, the leader of the research on the aging gene KAT7 of the CCTV special report, Professor Han Jingdong of Peking University, the creator of the new physiological age clock that is most suitable for the Chinese people, and Qu Jing and Zhang Weiqi of the Chinese Academy of Sciences, who are well-known in the field of aging. Before the spring thunder, in the "game of chess" with aging, Chinese scholars have already made a strong national voice first.
The blockbuster discovery was published in Cell Discovery, a top journal of Nature
Regenerative Power and Aging:
Will we end up "broken"?
Perhaps a gift from the Creator, most creatures have a certain ability to regenerate and repair tissues, just like geckos can re-grow their tails after escaping from a broken tail, and human blood, immune cells, and muscles can regenerate for a long time [2]. However, the precious regenerative power comparable to the "art of rebirth" is not equal, and there are huge differences between different species and even different ages of the same organism.
For example, mammals (humans, mice, etc.) have very limited regenerative ability, after the end of embryonic development, generally only bones, nerves, blood and other tissues can regenerate to a certain extent, such as the heart, which has a decisive role in life, but can not be "revived" [3]. In contrast, salamanders, planarians and other animals are much luckier, can be widely, multi-structure regeneration, and even full body regeneration.
In addition to their weak regenerative capacity, the regenerative repair of most species is greatly limited by aging, one of the reasons is that with age, stem cells and progenitor cells (that is, cells have a certain maturity, but can still undergo cell division) lose their self-renewal ability, change their proliferative activity, and reduce their function and potency, especially in humans [4, 5].
Note: There are significant differences in the regenerative capacity of different organisms. Image source[2]
But there is always a chance that many animals, such as hydra, planarians, zebrafish and salamanders, can miraculously "jump out" of the shackles of aging and maintain the regenerative ability to remain active throughout the life cycle [2].
Unlike the unassuming salamander, its regenerative capacity is not altered by recurrent regeneration and aging, and it is the only vertebrate capable of regenerating a full limb in adulthood,[6] due to its unique differentiated cell reprogramming[7] and strong stem cell regenerative capacity.[8]
Illustration: The regeneration of complex structures in classical models, ABCD is hydra, planarian, zebrafish and salamander. Image source[2]
Key pro-regenerative metabolites have been discovered!
To a reborn future without fear of aging
With super regenerative abilities + no fear of the threat of aging, these "gifted" creatures have successfully attracted the attention of scientists. In this study, Chinese scholars selected the classical regenerative model salamander and deer antler velvet, the only regenerative organ in mammals[9], and incorporated tissues or stem cells of primates (including humans) of different ages to try to find the root cause of the differences in regenerative ability associated with aging across species.
By analyzing a large amount of sequencing data, the researchers found that the expression of genes related to regenerative ability, whether between different species or in multiple tissues of the same organism, showed significant differences, and the differences between species (such as between salamanders and human stem cells) were particularly pronounced.
Note: Species or tissues with different regenerative abilities have significant differences in gene expression
Moreover, what is even more exciting is that under this seemingly complex and irregular change, further analysis shows that tissues with high regenerative capacity have similar metabolic expressions between tissues, but tissues with poor regenerative capacity have obvious differences in metabolic processes with high regenerative capacity tissues.
This seems to suggest that the "magic rebirth" in some animals that does not dissipate with the passage of time may have traces, and it is entirely possible that we will find the ultimate key regulator!
Note: Metabolomics characteristics of species and tissues with different regenerative abilities
And it turns out. Through the combing of many metabolic pathways one by one, the target is targeted at some products in the metabolic processes of fat, amino acids and nucleotides (the changes in these three major metabolic processes account for 60% of all metabolic changes), and finally the uridine in the nucleotide pathway is determined to be the core metabolic substance that determines the level of regeneration - the senescent human stem cells after uridine treatment are "reborn": regenerative ability is restored, genome stability is enhanced and mitochondrial activity is significantly improved.
Uridine in nucleotide metabolism is a key regulator of changes in aging-related regenerative capacity
Promote muscle regeneration, repair heart function,
Mention the outward manifestations of "old" rats,
Uridine is late
So, what is the sacredness of the slightly oddly named substance? Speaking of the full name of uridine , " uracil nucleoside " , it may be more familiar : it is composed of a nitrogen-containing base ( uracil ) + a molecule of ribose , which is essentially a nucleoside compound commonly used in the synthesis of RNA and membrane components [10].
Unexpectedly, this small molecule of human origin, which is widely present in vegetables and grains, has become a key substance affecting the ability to regenerate. Does this mean that bio-exogenous supplementation with uridine can provide tangible anti-aging effects?
Note: The main properties and uses of uridine
Thanks to the "full support" of the mice, we were able to initially solve the puzzle - uridine supplementation promoted the regeneration or repair of a variety of tissues in the mice, including skeletal muscle, heart, liver:
Promotes muscle tissue regeneration:
Uridine supplementation reduced the area where muscle fibrosis occurred, lowered the level of pro-inflammatory cytokines (eg, IL-6, TNF-α), and the treated mice showed stronger grip and longer running distances. Uridine upregulates muscle development-related pathways, such as nucleotide metabolism and small molecule biosynthesis processes, which promote the repair of up to 14 muscle cells.
Note: Uridine enhances the regenerative and repair capacity of muscle tissue in vivo
Improves heart function:
Uridine supplementation to the heart after myocardial infarction, compared with the control group, the heart function of the mice treated with uridine was greatly improved, such as left ventricular ejection fraction, serum lactate dehydrogenase, etc., and even gene expression was "dialed back" to the pre-disease state, and genes related to inflammatory factor secretion were significantly downregulated.
Note: Uridine promotes cardiac repair after myocardial infarction
In addition, uridine supplementation also restored carbon tetrachloride (CCl4)-induced liver damage, promoted hair regrowth and regeneration of damaged cartilage, and was no less than inferior in improving the external performance of elderly mice. When uridine was supplemented to elderly mice (22 months) for 2 consecutive months, their grip strength and exercise endurance, an important measure of aging, were significantly enhanced.
Figure Note: Uridine supplementation repaired the liver, cartilage and other tissues in the body, and improved the external performance of elderly mice
Time Pie reviews
"The book of rambling poetry is ecstatic", it is really appropriate to use this poem to describe the author when combing through the research. The memory still seems to stay at the annual meeting of the time faction last month, and the anti-aging colleagues exchanged the major events of 2021 on the spot, and the heavy research from Chinese scholars often appeared. However, only a few months later, Chinese scientists have been the first to discover another sharp blade against aging, the key metabolite of uroside, which promotes regeneration, and it can be said that the "Chinese era" of aging research has arrived!
Returning to this study, in my opinion, the article shows us only the "tip of the iceberg" in the series of trials - is there an optimal dose of uridine supplementation? Are there differentiated anti-aging effects for model organisms at different ages? Is it possible that the underlying mechanisms of its miraculous regenerative power could be further explored? And the public is very interested: is it possible for uridine to extend the healthy lifespan of organisms, how much can it be extended, and will it be the next star life extension substance? These questions may be fully answered in subsequent research reports.
—— TIMEPIE ——
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