To delay aging, can we really use young blood?

When it comes to delaying aging and "rejuvenation", modern people are no less obsessed with it than the ancients, and even more so. "Anti-aging magic drugs", anti-aging health products, fasting to prevent aging... are all hotly debated methods, and related research has frequently appeared in top academic journals.

Recently, a Nature magazine sub-journal reported a breakthrough study - proving that life is not powerless in the face of time, and the process of cell aging can be regulated by the environment. The method used is still the controversial blood exchange.

After exchanging blood between young and old mice, the research team found that signs of aging were quickly transmitted to the young mice through the blood, with muscle and visceral cells aging and strength and endurance declining. On the other hand, the old mice had improved muscle strength and physical endurance, and their athletic ability was restored.

It is impossible to do such experiments on humans, but researchers have also conducted some attempts at the cellular level. They cultured young human cells in the plasma of the elderly, and found that the expression of multiple aging-related genes increased within 6 days. This also proves that there may be "factors" in the plasma of the elderly that can make young cells age.

Irina M. Conboy, the corresponding author of this study, published a groundbreaking work in the field of "blood transfusion for anti-aging" as the first author. Irina is the founder of the method of connecting two mice for blood transfusion. In 2005, she reported a study on the mechanism of "blood transfusion for anti-aging" in the journal Nature, laying the foundation for this field. It has been cited more than 2,200 times. Today, the male-female mouse connectome and the young-aged connectome have become a mature research system and method.

So, what new progress has Irina made in this new research?

The researchers connected two mice of different ages together for "alien symbiosis" and performed a single blood exchange. The two mice exchanged this time were a young mouse of 3 months old and an old mouse of about 22-24 months old. Seven days after the blood exchange, the researchers conducted a physical test on the two mice - letting them run on the running wheel until exhaustion. The results showed that mice injected with aged blood persisted for a shorter time and were more prone to fatigue than ordinary mice of the same age. More signs of aging, such as renal fibrosis, were also found in their kidneys and livers. The other old mouse injected with young blood was "youthful". Its blood lipids and fibrosis indicators decreased, and its muscle endurance and anti-fatigue conditions improved.

The researchers speculate that blood from old mice releases the senescence-associated secretory phenotype (SASP) in the blood, which can cause muscle weakness, decreased endurance, tissue damage, etc., which are signs of aging. The senescence-associated secretory phenotype refers to the release of some secretory factors by aging cells, which affect the surrounding "young" cells and promote the aging of young cells. It is regarded as one of the key characteristics of aging. If the old mice are given the drug "dasatinib + quercetin" to clear senescent cells before blood exchange, the signs of aging in young mice will be significantly weakened. This shows that the senescence-associated secretory phenotype of old mice that have cleared senescent cells will be greatly weakened.

So, specifically at the molecular mechanism level, what changes occurred after the two mice exchanged blood?

The researchers conducted in vitro experiments. They cultured primary cells from mice and humans in young/old mouse serum and young/old human plasma. The results of the comparison of serum from 4-month-old young mice and 32-month-old old mice showed that the expression of the aging up-regulated gene Cdkn2a increased and the expression of the aging down-regulated gene Lmnb1 decreased in the serum of old mice.

Here, upregulation means that the gene is positively regulated when it is transcribed into mRNA, that is, the expression is promoted; downregulation is the opposite. The expression of β-galactosidase (SA-β-gal) associated with upregulation of aging increases, while cell proliferation decreases.

Moreover, when the serum of young mice and the serum of old mice accounted for half each, the aging of the mouse cells after treatment was comparable to that after cultured with 100% old mouse serum. In other words, the content of factors promoting aging in the serum of old mice is very high, and diluting it by half will not affect the effect of promoting aging. In addition, the researchers also cultured human kidney cells in the blood environment of 60-70-year-old people. After 6 days of the experiment, many aging markers were found in the cells.

However, if kidney cells are cultured in the blood of 20-30-year-old humans, this phenomenon will not be found. Finally, the researchers said that the above experiments show that regulating various aging factors including SASP can be a strategy for anti-aging and life extension. The "blood transfusion method" once again shows that it is worthy of attention in delaying aging. Although the specific mechanism is still unclear, some people can't wait to try it.

The earliest mouse "alien symbiosis" experiment caused a sensation, and the outside world quickly interpreted it as some beneficial components in young blood can play a "rejuvenation" effect. However, Irina herself believes that this cannot explain all the problems, and another aspect is that the harmful components in the blood of old mice have been diluted.

To confirm this, Irina's team later published another study, diluting the plasma of young mice and old mice by 50% with saline. As a result, nothing bad happened to the young mice, and the mice quickly replenished the missing plasma and remained young. However, the old mice regained their vitality significantly. In addition to strengthening their muscles and internal organs, neuroinflammation in the brain also decreased, showing improved cognitive ability.

At the same time, as the research direction of blood transfusion becomes more and more popular, some key components of young blood have been identified.

A study from the University of Pittsburgh showed that injecting young mouse blood into injured old mice can accelerate muscle regeneration. The research team proved through experiments that this is related to extracellular vesicles (EVs). If the extracellular vesicles are removed and then a "blood transfusion" is performed, the effect will disappear.

Another study from Stanford University injected the blood of mice that had been exercising continuously for a month into sedentary fat mice and observed that the sedentary mice performed better in memory tests and had lower levels of brain inflammation.

This time it is the clusterin in the blood that is at work. Clusterin levels in the blood increase after exercise, and when injected into sedentary mice, it can inhibit inflammatory signals.

Finally, it should be said that whether it is blood exchange or plasma dilution, the academic community still mainly relies on animal experiments and in vitro human experiments, and the effectiveness and risks of clinical applications still need further exploration.

But this cannot stop people's determination to pursue "immortality". In 2016, the American company Ambrosia provided young people's blood to the rich at a price of $8,000 per course of treatment. The project was stopped by the FDA in 2019. Nikolay Sidorov, a Russian madman who calls himself a biohacker, tested Irina's plasma dilution method on himself and volunteers. After three dilutions, he described himself as feeling energetic. It was like drinking a few cups of coffee in the morning, but this state could last for several days.

Thank you for reading this article. Learn about genes and live a wonderful life. Pay attention to the little things about genes and learn about genetic knowledge that can make your life more wonderful.

This article is a work supported by Science Popularization China Starry Sky Project

Team/Author Name: Tiangeng

Review: Tao Ning

Produced by: China Association for Science and Technology Department of Science Popularization

Producer: China Science and Technology Press Co., Ltd., Beijing Zhongke Xinghe Culture Media Co., Ltd.