Old plasma dilution reduces human biological age: a clinical study

Abstract

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.

Plasma Exchange Reduces Aβ Levels in Plasma and Decreases Amyloid Plaques in the Brain in a Mouse Model of Alzheimer’s Disease

“…Besides the possibility of Aβ removal from plasma and a putative role of albumin in PE, there are other possible effects reported for this treatment that could have actively but indirectly contributed to the observed results. For example, it has been suggested that PE has the ability to reduce pro-aging phenotypes through its dilutive effect on old plasma, leading to a switch toward a younger proteome signature and a pro-regenerative phenotype [54]. In support of this, a study conducted using mouse models found that the replacement of old plasma with a 5% albumin solution induced broad rejuvenation changes in different tissues [55].…”

Evaluation of quantitative biomarkers of aging in human PBMCs

“…It may be difficult to identify cellular markers of aging if these are heavily influenced by extrinsic factors like cell signalling, nutrient availability, and waste accumulation ( López-Otín et al, 2023 ). Heterochronic parabiosis and plasma exchange experiments demonstrate cells can be rejuvenated by exposure to young plasma or by dilution of old plasma with saline ( Villeda et al, 2011 ; Conboy and Rando, 2012 ; Elabd et al, 2014 ; Rebo et al, 2016 ; Kang and Yang, 2020 ; Mehdipour et al, 2020 ; Kim et al, 2022 ). A cell culture model of aging must acknowledge that both the breakdown in cellular functions and the tissue environment are important.…”

Long-term human spaceflight and inflammaging: Does it promote aging?

“…However, the possibility to implement therapies or treatments that may modulate NF-κB seems at the moment unlikely, due to the wide pleiotropy of this transcription factor. On the other hand, a recent work appears to pave the way for the decrease of molecular inflammatory profile at systemic level, thus likely counteracting inflammaging and reducing human biological age (Kim et al, 2022).…”