This study is interesting on a few counts. Firstly, transfusion of old individuals with plasma from young individuals has failed to produce usefully large benefits in human trials, and the evidence in mice looks similarly shaky. Yet here, in rats, benefits are observed with a specific approach to producing a plasma fraction for use in therapy. The authors do not divulge details regarding the methodology of production, as they intend commercial development in the near future. Secondly, it connects epigenetic age reduction with reduction in senescent cell burden. It is worth noting that the epigenetic clocks used here to assess biological age are new, not existing clocks, however. The reduction in senescent cells is thus the more interesting measure to result from the study. As a final note, only a small number of rats were used in the plasma transfusion portion of the study, so this is very much a result that requires replication.

Young blood plasma is known to confer beneficial effects on various organs in mice. However, it was not known whether young plasma rejuvenates cells and tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly-accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n=593 tissue samples. As indicated by their respective names, the rat pan-tissue clock can be applied to DNA methylation profiles from all rat tissues, while the rat brain-, liver-, and blood clocks apply to the corresponding tissue types. We also developed two epigenetic clocks that apply to both human and rat tissues by adding n=850 human tissue samples to the training data.

We employed these six clocks to investigate the rejuvenation effects of a plasma fraction treatment in different rat tissues. The treatment more than halved the epigenetic ages of blood, heart, and liver tissue. A less pronounced, but statistically significant, rejuvenation effect could be observed in the hypothalamus. The treatment was accompanied by progressive improvement in the function of these organs as ascertained through numerous biochemical/physiological biomarkers and behavioral responses to assess cognitive functions. Cellular senescence, which is not associated with epigenetic aging, was also considerably reduced in vital organs. Overall, this study demonstrates that a plasma-derived treatment markedly reverses aging according to epigenetic clocks and benchmark biomarkers of aging.