International Business Department           Liu Bojia           April 19, 2023

  We all know that the gradual ageing of life is inevitable. As we age, the ability of cells responsible for maintaining homeostasis and repairing damage gradually diminishes, ultimately leading to functional decline of tissues. In addition to natural aging, some chronic diseases can even further accelerate the aging process of the body. But is there a way to slow down the body's aging rate, or even reverse the aging process?

  More than 20 years ago, scientists set their sights on younger individuals. Specifically the blood of younger individuals is likely to have a role in revers ing aging. For example, after connecting the circulatory system of young mice to that of older mice through surgery, several tissues and organs of the older mice recovered their function, with positive effects on the muscles, liver and brain.

  But with so many blood components, it remains unclear which molecules play a key role, and with direct blood exchange in the body impractical for the average person, it is important to find the components that specifically play a role in reversing aging.

  In a new paper published in Nature Aging, a team of researchers from Nanjing University and Nanjing Gulou Hospital collaborated to discover that extracellular vesicles (EVs) in young blood may hold the key to rejuvenation we've been looking for. Originally responsible for regulating intercellular communication and maintaining tissue homeostasis, the new study found that EVs in young mice significantly reversed aging in older individuals and extended lifespan.

  Of course, this isn't the first time that EV has been found to have the potential to reverse aging, as a 2021 study, also from Nature Aging, suggests that removing EV from the blood of young mice deprives the young blood of its ability to help repair muscle in older individuals, as Klotho, a protein contained in EV, is essential for anti-aging.

  In the new study, the authors wanted to test the role of EV in reversing aging in a broader dimension. To do this, they tried extracting and purifying small extracellular vesicles (small EV, sEV) from the blood of young mice (aged 2 months), which were then injected into older mice (aged 20 months) at a weekly frequency at a reasonable dose.

  As a result, the median lifespan of mice injected weekly with young sEVs increased by 12.42% compared to the control group - the median lifespan of mice in the experimental group was 34.4 months, compared to 30.6 months for control mice. At the same time, weekly injections of young sEV resulted in younger looking mice, and although the mice's hair colour turned grey, their hair loss process was greatly inhibited.

  In addition, the researchers have established an assessment system to determine the degree of debility in mice. According to their analysis, injection of young sEV significantly reduced the frailty index of mice, and defects in the muscular and skeletal systems were greatly improved. On top of that, the heart function of the experimental mice became healthier, the brain's associative and spatial memory was better than that of control mice of the same age, and their exercise endurance was longer lasting.

  Even more surprisingly, the fertility of the older male mice injected with YEV was restored, and the total number of spermatozoa and sperm viability were significantly improved. The authors' calculations showed that the biological age of the experimental mice was only about 15.1 months at the actual age of 24 months, so it can be said that weekly injections of young sEVs allowed the older mice to fully reverse aging!

  Mechanistically, the young sEV that entered the mice improved mitochondrial function, increasing mitochondrial volume and allowing the mitochondria to supply more ATP. analyses of the data showed that mitochondrial energy metabolism in the experimental mice improved, resisting the mitochondrial defects that would otherwise be associated with aging.

  In addition to the observation of EV, the researchers additionally compared other components of young and old mice. For example, microRNAs (miRNAs) belong to a class of blood markers that change with aging, with those pro-aging miRNAs accumulating more as they age, while anti-aging, youth-related miRNAs are gradually lost. By detecting the balance between these two types of miRNAs, it is possible to predict an individual's aging process.

  Based on these findings, the authors believe that in the future it will be possible to use sEVs from young individual sources to help with anti-aging after determining that aging is occurring too rapidly. Since sEVs do not cause toxicity or immunogenicity, they could help with aging faster and simpler than targeting hard-to-target targets such as telomeres.