Old plasma dilution reduces human biological age: a clinical study

Area of Science:

• Gerontology
• Molecular Biology
• Biochemistry

Background:

• Animal studies suggest blood heterochronicity influences aging.
• Human aging may involve systemic molecular excess.
• Biological age requires a novel, direct measurement.

Purpose of the Study:

• To extrapolate animal findings on blood heterochronicity to humans.
• To establish a direct measurement for biological age.
• To investigate if reducing molecular excess can reverse biological age.

Main Methods:

• Developed a novel direct measurement of biological age based on protein biomarker deregulation.
• Administered therapeutic plasma exchange (TPE) to participants.
• Analyzed systemic proteome, cellular senescence, DNA damage, and signaling pathways (JAK-STAT, MAPK, TGF-beta, NF-κB, TLR4).
• Utilized big-data gene expression studies for validation.

Main Results:

• Therapeutic plasma exchange (TPE) reversed biological age.
• TPE promoted a younger systemic proteome, restoring regenerative and anticancer regulators.
• Youthful profiles of myeloid/lymphoid markers, reduced cellular senescence, and lower DNA damage were observed.
• Normalization of Toll-like receptor 4 (TLR4) was identified as a key nodal point in molecular rejuvenation, balancing key signaling pathways.

Conclusions:

• Human aging is driven by systemic molecular excess, which can be attenuated to reverse biological age.
• Therapeutic plasma exchange (TPE) effectively rejuvenates the systemic proteome and cellular characteristics.
• Normalization of TLR4 signaling is a critical mechanism for achieving molecular rejuvenation and reversing biological age.