Old plasma dilution reduces human biological age: a clinical study

• Published in: GeroScience 2022-12, Vol.44 (6), p.2701-2720
• Main Authors: Kim, Daehwan, Kiprov, Dobri D., Luellen, Connor, Lieb, Michael, Liu, Chao, Watanabe, Etsuko, Mei, Xiaoyue, Cassaleto, Kaitlin, Kramer, Joel, Conboy, Michael J., Conboy, Irina M.
• Format: Article
• Language: English
• Subjects: Age; Aging; Animals; Apoptosis; Biomedical and Life Sciences; Cell Biology; Cellular Senescence; DNA damage; Gene expression; Geriatrics/Gerontology; Humans; Life Sciences; MAP kinase; Mice; Molecular Medicine; NF-kappa B - metabolism; NF-κB protein; Original; Original Article; Proteomes; Senescence; Signal Transduction; TLR4 protein; Toll-like receptors; Transforming Growth Factor beta
• ISSN: 2509-2715; 2509-2723
• DOI: 10.1007/s11357-022-00645-w

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.