Rejuvenation of the Systemic Environment (University of California, Berkeley)

Rejuvenation of the Systemic Environment

Principal Investigator: Irina Conboy

Research Team: Keith Causey, Justin Rebo

Cells exist within in a complex network of communication, mediated by signaling molecules. The core of the degenerative aging process is the accumulation of damage to cells and biomolecules, which triggers them to change their signaling patterns accordingly. The full network of such signals is powerfully demonstrated by experiments in heterochronic parabiosis, in which the circulation of an aged animal is joined to that of a young one, exposing the aged organism’s tissues to a youthful systemic environment (and vice-versa). 
 
Many studies have confirmed that parabiosis with a young animal partially rejuvenates many aspects of an aged organism’s cell and tissue function, including the regenerative capacity of tissue-specific stem cells. This research provides a useful means of studying the systemic environment as the interface for the application of multiple potential rejuvenation interventions.
 
The UC Berkeley team explored the influence of the systemic environment on aging processes using a novel computer-controlled technological platform and specialized hardware made from off-the-shelf and custom 3-D printed parts. This platform enabled the group to easily, safely, and non-surgically extract blood or plasma from laboratory animals, process that blood in any of several ways, and ultimately return it to the original animal, exchange it with that of an oppositely-aged animal, or extract or concentrate specific factors present in those biological fluids before returning it into the living environment or testing its effects in in vitro systems. The system also offers a way for scientists to disentangle the effects of the soluble factors in the shared systemic environment from the effects of an old animal having access to the young animal’s blood cells and organs (and vice-versa). This feature will be important for any potential to translate the effects of heterochronic parabiosis to humans.
 
The UC Berkeley team has now successfully used the system to perform the first set of exchanges, comparing animals subjected to full heterochronic blood exchanges with old animals that have undergone one-way transfer of young blood; young animals that have received one-way transfer of old blood; and young and old same-aged animals that have undergone full blood exchange. They have furthermore tested the effects of these transferred systemic environments on the ability of the mice’s muscles to mount a regenerative response after injury, with the analysis of the regenerating muscle cells still pending. The team also isolated the brains, livers and hearts of these animals postmortem, and assessed the effects of the transferred systemic environments on the proliferation of stem and progenitor cells in these tissues under baseline conditions.