To prevent getting lost, the elevator goes directly to the safety island to report Liu Yadong A
Source: Metz Medicine
Author: Swagpp
From the Taoist pursuit of "feathering and ascending to immortals, immortality" to the Norse mythology of "the goddess of youth Eton and her golden apple", people have had an endless yearning for "longevity" since ancient times, but many stories of the pursuit of immortality have ended in failure. Even today, scientists are still searching to understand the meaning of aging.
Aging, which usually refers to the process of functional decline of an organism from adulthood, is an inevitable, multi-stage, and gradual process. Mechanistically, the aging process is mainly due to the gradual accumulation of random damage in cells, organelles and macromolecules, but the specific mechanism of damage is still unknown.
The exploration continues, and the pursuit continues. In December 2022, Cell released Hallmarks of aging: An expanding universe, which unveiled 12 markers of aging, including: genomic instability, telomere depletion, cellular senescence, altered cell-cell communication, dysbiosis, etc. If these markers are stimulated, they can accelerate aging, while targeted interventions can slow down or even reverse aging.
12 Aging Markers
In recent years, there has been a steady stream of research on one of the 12 major features of aging, altered cell-to-cell communication, which is often inseparable from blood. In fact, circulating molecules in the blood are a major contributor to aging, leading to impaired tissue communication and further aging-related degeneration.
Based on this, scientists have developed a method of "rejuvenation" - heterochronic parabiosis. In this way, the researcher connects the circulatory systems of two different ages (one old and one young) together to form a shared circulatory system. The blood from the young mice rejuvenated the brain, heart, liver, skeletal muscle, and so on of the old mice.
Sounds a bit like "rejuvenation"? What kind of "rejuvenation" factor exists in young blood?
Recently, a team from the School of Life Sciences of Nanjing University has discovered the key to opening the "magic box" of longevity! Researchers injected small extracellular vesicles (sEVs) from the plasma of young mice into the body of old mice, which can extend the life of the latter by 12.42% and show a healthier state, including higher glossy hair, stronger fertility, healthier metabolic level, stronger cognitive ability and so on.
What's even more amazing is that the injection of sEVs made the "longest-lived" mice live to 1266 days, which is equivalent to 120-130 years old in humans!
doi: 10.1038/s43587-024-00612-4
First, the researchers built a 2-month-old juvenile and 20-month-old male mouse models, and purified sEVs from plasma. 200 μl of juvenile sEVs are injected intravenously into elderly male mice, containing 1.80 μg of total protein per microliter, once a week until death, and the control group is injected with the same volume of PBS.
Survival analysis showed that weekly injection of juvenile sEVs significantly extended the median lifespan of aged mice. After sEVs injection, the lifespan of mice was extended to 34.4 months, while the lifespan of the control group injected with PBS was 30.6 months, and the former was 12.42% longer than the latter.
The longest-lived mice lived to 1,266 days, which is equivalent to 120-130 years in humans! This longevity far outweighs the effects of calorie-restricted diets, metformin, and niacinamide.
In addition, after receiving treatment with young sEVs, the elderly mice were rejuvenated in a short period of time – their hair was darker and shiny, and they could even walk with wind under their feet. Specifically, the older mice also looked healthier, preventing the development of alopecia areata, and the treatment of sEVs improved the frailty index of the older mice.
Effect of injection of young sEVs on lifespan and hair in mice
In the long run, the "rejuvenation" brought by the injection of juvenile sEVs is systemic and long-lasting! Fertility is significantly improved, metabolic health is "rejuvenated", heart performance is significantly improved, and even brain atrophy is alleviated. In other words, sEVs treatment returns the morphology and performance of aged tissues and organs to a "younger" state.
So, the question arises: since young sEVs can improve the physiological and behavioral level of older mice, will injecting old sEVs into young mice make them "white-headed overnight"?
Sure enough, young mice treated with elderly sEVs became more susceptible to exhaustion during the treadmill run test and showed worse memory in the Morris water maze test. That is, old sEVs led to a rapid decline in memory function and exercise tolerance in young mice. Therefore, it can be determined that sEVs largely mediate the regulation of plasma aging.
Effect of young sEVs on multi-organ tissues
At a deeper level, young sEVs cause changes at the proteomic level, such as significant changes in the spleen, hippocampus, and lung tissue. In fact, gene ontology (GO) enrichment analysis showed that sEVs were able to reverse age-related degenerative changes through a variety of mechanisms, including the regulation of mitochondrial dysfunction, epigenetic alterations, and genomic instability.
Mechanistic studies have shown that young sEVs can stimulate the expression of receptor γ helper activator 1α (PGC-1α) in vivo and in vitro, thereby improving mitochondrial function, making up for mitochondrial defects in aging tissues, and achieving "rejuvenation".
sEVs中miRNA能调节PGC-1α表达来影响线粒体代谢
For a long time, the story of "blood transfusion rejuvenation" has fascinated many people, and even pinned the hope of "immortality" on the exchange of blood.
In fact, as early as 2021, a study in Nature explored the effect of blood transfusion therapy - by transfusing the blood of young mice into the body of elderly mice, the muscles of elderly mice can be rejuvenated. At the time, the study confirmed the important role of extracellular vesicles as carriers of anti-aging components.
Coincidentally, a new study in Nature has shown another effect of exchange transfusion, alleviating Alzheimer's disease! The study found that whole blood exchange with healthy individuals significantly reduced the formation of amyloid plates in the brain by 40%-80%, and even improved spatial memory.
However, the safety and efficacy of exchange transfusion are highly debated, so it is even more important to find the key components in young blood. Young sEVs, as a natural carrier present in the blood circulation, do not produce toxicity or immunogenicity, or become an effective way to "stay young".
Imagine if one day "sEVs injections to improve aging" came true, would you be willing to give it a try?
参考资料：[1]Chen X, Luo Y, Zhu Q, Zhang J, Huang H, Kan Y, Li D, Xu M, Liu S, Li J, Pan J, Zhang L, Guo Y, Wang B, Qi G, Zhou Z, Zhang CY, Fang L, Wang Y, Chen X. Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism. Nat Aging. 2024 Apr 16. doi: 10.1038/s43587-024-00612-4. Epub ahead of print. PMID: 38627524. [2] Urayama, A., Moreno-Gonzalez, I., Morales-Scheihing, D. et al. Preventive and therapeutic reduction of amyloid deposition and behavioral impairments in a model of Alzheimer’s disease by whole blood exchange. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01679-4