Heterochronic parabiosis, involving the mixing of young and old blood, has been explored for several years with the hope of reversing biological aging and combating age-related diseases. Experiments on animal models have demonstrated that transferring young blood into an old organism extends its lifespan. The observed effects, manifesting at the tissue level, suggest that they result directly from transferable plasma factors. These findings have led to extensive research aimed at identifying and isolating these potential factors.
However, in the biology of aging, it is crucial to differentiate between improving organ health or function and truly reversing age at the molecular level. While the former can be achieved through drugs or surgical interventions, the clinical biomarkers identified so far are insufficient to precisely establish the fundamental mechanisms associated with the latter.
The new study, published in the GeroScience journal, aimed to determine if treatments based on heterochronic parabiosis could genuinely reverse biological age. The experiment also marks the world’s first case of interspecies epigenetic transfer. “This study aimed to answer the following question: Does young pig plasma reverse the biological age of rat tissues?” explain the experts from the University of California and the Yuvan Research Laboratory in their paper.
An Analysis Based On Six Epigenetic Clocks
Epigenetic changes, such as methylation and glycosylation, are well-established features of aging. The difference between methylation age and chronological age, for example, is predictive of mortality (all-cause) and is associated with a wide range of age-related pathologies, such as neurodegeneration. In the new study, six distinct epigenetic clocks were used to quantify the rate of aging in rats. Among these clocks are methylation and glycosylation, both applicable to humans.
On the other hand, analyses of human immunoglobulin G (IgG) have shown that changes in its N-glycome composition occur with aging and age-related pathological conditions. This pathway provides a glycan clock that can indicate molecular age and may be reversed through lifestyle changes. In addition to the epigenetic clocks, the researchers in the study conducted profiling of IgG N-glycans as well as physiological, histological, biochemical, and cognitive assessments.
Bringing An 80-year-old Person Back to 26 Years?
The E5 treatment, administered to rats aged up to 2.3 years, is composed of plasma nanoparticle fractions from young pigs. These fractions include exosomes, extracellular vesicles carrying bioactive molecules involved in intercellular communication, anti-tumor activity, tissue regeneration, and immune response, all vital functions that deteriorate with age. Among these molecules are a wide range of proteins, lipids, microRNAs, and mRNAs.
Furthermore, the treatment is based on the principle of heterochronic plasma exchange and does not involve the physical attachment of the circulatory systems of both animals (the pig and the rat). This has the advantage of significantly reducing stress-induced stress. Moreover, a young rat weighs approximately half as much as an old rat and could only replace 50% of the latter’s plasma. In contrast, a pig, due to its size, can replace 100% of an old rat’s blood.
After only a few days of treatment, the rats experienced a remarkable reversal of biological age, with an average of 67.4%. In another experiment, aging rats saw a 77.6% rejuvenation of their livers. Similar results in humans could bring an 80-year-old person back to a biological age of 26.
Aside from humans, the treatment could potentially be applied to other animals, extending the lifespan of pets, for example. Furthermore, it could contribute to the conservation of endangered species. Indeed, if used in a controlled and responsible manner, this treatment might, over the long term, help rebalance the conservation status of certain species and restore entire ecosystems. However, many challenges remain to be overcome before considering clinical applications.