The Journal Club returns to our Facebook page on Tuesday 30th August at 12:00 Eastern with your host, Dr. Oliver Medvedik.
This month, we investigate a paper, Old plasma dilution reduces human biological age: a clinical study, in which Irina Conboy and her team investigated the effects of therapeutic plasma exchange on aging in people. Previous experiments by the same team have focused on mice and demonstrated rejuvenation; this paper is the first step towards translating those results to humans. Could this be the first demonstration in people that aging can be reversed? Tune in to find out!
This work extrapolates to humans the previous animal studies on blood heterochronicity and establishes a novel direct measurement of biological age. Our results support the hypothesis that, similar to mice, human aging is driven by age-imposed systemic molecular excess, the attenuation of which reverses biological age, defined in our work as a deregulation (noise) of 10 novel protein biomarkers. The results on biological age are strongly supported by the data, which demonstrates that rounds of therapeutic plasma exchange (TPE) promote a global shift to a younger systemic proteome, including youthfully restored pro-regenerative, anticancer, and apoptotic regulators and a youthful profile of myeloid/lymphoid markers in circulating cells, which have reduced cellular senescence and lower DNA damage. Mechanistically, the circulatory regulators of the JAK-STAT, MAPK, TGF-beta, NF-κB, and Toll-like receptor signaling pathways become more youthfully balanced through normalization of TLR4, which we define as a nodal point of this molecular rejuvenation. The significance of our findings is confirmed through big-data gene expression studies.