Editors' ChoiceLEARNING AND MEMORY

Young Blood Rejuvenates the Aging Brain

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Science Translational Medicine  28 May 2014:
Vol. 6, Issue 238, pp. 238ec95
DOI: 10.1126/scitranslmed.3009412

Vampires may rise nightly at twilight, but with their blood-based diet, they’ll never experience their twilight years—or the associated deterioration in cognitive function. Among nonvampires, aging is the primary risk factor for dementias such as Alzheimer’s disease. As the aged population expands, so does the prevalence of cognitive impairment, making the identification of strategies to counteract deterioration in brain function a priority. To address this issue, Villeda et al. revive an old technique, termed "heterochronic parabiosis," which involves surgically connecting the circulatory systems of two mice, one young and one old, so that they share blood.

Previous studies have demonstrated that instilling young blood into an old rodent can rejuvenate peripheral tissues, such as liver and muscle, and can stimulate the birth of new nerve cells in the brain. The authors show that this method can also counteract age-related declines in learning and memory by activating specific signaling pathways in the hippocampus, a region of the brain involved in learning. First, they identified families of genes that are altered in the hippocampus when young and old mice share blood. This information led to the discovery of age-related declines in the expression of many genes involved in synaptic plasticity, the molecular process by which neurons form new connections. These declines were prevented by heterochronic parabiosis, suggesting that young blood can directly counteract detrimental aspects of the aging process in the brain. Regular injections of young blood into old animals had a similar effect. Young blood also prevented both electrophysiological and behavioral deficits in learning and memory in old mice. The authors found that levels of phosphorylated Creb, a transcription factor known to be instrumental in learning and memory, increased significantly when old mice received young blood. Furthermore, they found that by lowering Creb levels, the restorative effects of young blood on the hippocampus were blocked. Thus, they concluded that young blood enhances cognition in old animals via a Creb-dependent mechanism.

These experiments raise the fascinating possibility that transfusion of blood or specific bloodborne factors from young humans might rejuvenate the aged human brain. Although subjecting large populations of elderly people to blood transfusions from young donors is unlikely to be clinically feasible, the use of specific active molecules in young blood as antiaging therapeutics might be. Unfortunately, this paper did not go so far as to identify the brain-saving factors in young blood. Further studies are needed to identify these factors and to evaluate the efficacy of this intervention in older humans.

S. A. Villeda et al., Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat. Med. 10.1038/nm.3569 (2014). [PubMed]

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