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A Review of the State of Heterochronic Parabiosis Research

To follow on from yesterday's article on trials of blood transfusions from young to old, here is an open access review paper from some of the researchers involved. A range of tests and scientific programs have grown out from heterochronic parabiosis research in which the circulatory systems of an old and a young laboratory animal are joined. This produces benefits in the older animal and negatively impacts the younger animal. Researchers are now searching for the underlying mechanisms and signals that cause these reactions, so as to build therapies that might, for example, increase stem cell activity in the old.

In the modern medical era, more diverse and effective treatment options have translated to increased life expectancy. With this increased life span comes increased age-associated disease and the dire need to understand underlying causes so that therapies can be designed to mitigate the burden to health and the economy. Aging exacts a seemingly inevitable multisystem deterioration of function that acts as a risk factor for a variety of age-related disorders, including those that devastate organs of limited regenerative potential, such as the brain.

Rather than studying the brain and mechanisms that govern its aging in isolation from other organ systems, an emerging approach is to understand the relatively unappreciated communication that exists between the brain and systemic environment. Revisiting classical methods of experimental physiology in animal models has uncovered surprising regenerative activity in young blood with translational implications for the aging liver, muscle, brain, and other organs. Soluble factors present in young or aged blood are sufficient to improve or impair cognitive function, respectively, suggesting an aging continuum of brain-relevant systemic factors.

The age-associated plasma chemokine CCL11 has been shown to impair young brain function while GDF11 has been reported to increase the generation of neurons in aged mice. However, the identities of specific factors mediating memory-enhancing effects of young blood and their mechanisms of action are enigmatic. Here we review brain rejuvenation studies in the broader context of systemic rejuvenation research. We discuss putative mechanisms for blood-borne brain rejuvenation and suggest promising avenues for future research and development of therapies.

Link: http://dx.doi.org/10.1001/jamaneurol.2015.1616

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