Young Blood Revitalizes the Aging Brain




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Have neuroscientists found the proverbial fountain of youth? The idea may not be as far-fetched as you think. Researchers recently reported that infusing blood from young mice into the circulation of elderly mice is sufficient to reverse brain aging.

Considering the increase in the proportion of elderly humans, the identification of new ways to maintain or enhance cognition during aging is of primary importance. Normal brain aging is marked by cellular and molecular changes thought to mediate cognitive decline. Researchers have long sought to increase the integrity of the aged brain in animal models. However, only recently, researchers have revived a century-old method, known as parabiosis, to help rescue the aging brain from decline.

The study, conducted by Tony Wyss-Coray, Professor in the Department of Neurology and Neurological Sciences at Stanford University School of Medicine, in collaboration with researchers at the University of California at San Francisco, the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, the AfaSci Research Laboratory, and the VA Palo Alto Health Care System, was published in the May 2014 issue of Nature Medicine.

To facilitate the transfer of blood from young (3 months) to aged (18 months) mice, the researchers surgically joined young and aged mice (so that they shared the same circulatory system) for five weeks or injected young blood into the tails of aged mice. Previously, the researchers utilized similar methods to show that exposure to young blood increased stem cell function in the brains of aged mice. In the current studies, the researchers sought to investigate whether exposure to young blood could improve molecular, physiological, and behavioral measures of learning and memory in aged mice.

Aged mice exposed to young blood for five weeks showed a significant increase in the number of cells in the hippocampus, a structure important for learning and memory, positive for signaling molecules (including Erg-1, c-Fos, and pCREB) important for learning processes. In addition, these aged mice showed a significantly increased number of dendritic spines, portions of brain cells that receive signals in order to help transmit information, in the dentate gyrus of the hippocampus. In brain slices prepared from these mice, a physiological process that underlies learning, known as long-term potentiation, was significantly enhanced in the dentate gyrus of aged mice exposed to young blood. Importantly, the parabiosis procedure itself did not cause significant changes in general health, behavior, or stress response in the mice that were surgically fused together.

“We’ve shown that at least some age-related impairments in brain function are reversible. It was as if these old brains were recharged by young blood,” said Dr. Wyss-Coray.

Additional studies showed that aged mice exposed to young blood showed enhanced learning in two behavioral models of memory that depend on the hippocampus – the radial arm water maze and contextual fear conditioning. Lastly, the researchers showed that CREB signaling was necessary for the increase in dendritic spines observed in the dentate gyrus of aged mice and contributes significantly to the enhancement of behavioral learning and memory in aged mice.

“There are factors present in blood from young mice that can recharge an old mouse’s brain so that it functions more like a younger one,” said Dr. Wyss-Coray. “We’re working intensively to find out what those factors might be and from exactly which tissues they originate. We don’t know yet if this will work in humans,” he said.

References

Bishop NA, Lu T, & Yankner BA (2010). Neural mechanisms of ageing and cognitive decline. Nature, 464 (7288), 529-35 PMID: 20336135

Bliss TV, & Collingridge GL (1993). A synaptic model of memory: long-term potentiation in the hippocampus. Nature, 361 (6407), 31-9 PMID: 8421494

Conboy MJ, Conboy IM, & Rando TA (2013). Heterochronic parabiosis: historical perspective and methodological considerations for studies of aging and longevity. Aging cell, 12 (3), 525-30 PMID: 23489470

Hebert LE, Scherr PA, Bienias JL, Bennett DA, & Evans DA (2003). Alzheimer disease in the US population: prevalence estimates using the 2000 census. Archives of neurology, 60 (8), 1119-22 PMID: 12925369

Rosenzweig ES, & Barnes CA (2003). Impact of aging on hippocampal function: plasticity, network dynamics, and cognition. Progress in neurobiology, 69 (3), 143-79 PMID: 12758108

Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A, Lucin KM, Czirr E, Park JS, Couillard-Després S, Aigner L, Li G, Peskind ER, Kaye JA, Quinn JF, Galasko DR, Xie XS, Rando TA, & Wyss-Coray T (2011). The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature, 477 (7362), 90-4 PMID: 21886162

Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, Smith LK, Bieri G, Lin K, Berdnik D, Wabl R, Udeochu J, Wheatley EG, Zou B, Simmons DA, Xie XS, Longo FM, & Wyss-Coray T (2014). Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nature medicine PMID: 24793238

Image via Fer Gregory / Shutterstock.

Dario Dieguez, Jr, PhD

Dario Dieguez, Jr., Ph.D., spent over a decade conducting neuroscience research relevant to cognitive brain aging. He worked as a Science Writer in the Office of the National Institutes of Health (NIH) Director Elias Zerhouni, M.D. and at NIH's Center for Scientific Review. He taught Cellular Biology and Neurochemistry at the University of Texas at San Antonio and Cognitive Psychology at Boston University. For several years, he worked as a consultant for Pearson, Inc. and as a freelance science writer, with several clients in the U.S., Canada, Australia, and Germany. As a Research Program Manager at the Lupus Foundation of America, he oversaw the awarding of millions of dollars for research and was integral to the launching of Lupus Science and Medicine, an open access journal. Currently, he works as a Health Scientist Administrator at the Society for Women's Health Research and is an Adjunct Professor of Psychology and Bioethics at The Washington Center.
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