Editors' ChoicePhysiology

Bettering Your Elders

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Science Signaling  13 May 2014:
Vol. 7, Issue 325, pp. ec125
DOI: 10.1126/scisignal.2005463

Reductions in cognition, healing, and physical endurance are inevitable natural consequences of aging. Age-related declines in cognitive function are associated with decreased neurogenesis and changes in brain microvasculature that reduce blood flow. Muscles in aged mice have fewer stem cells than those in young mice, and these stem cells have greater accumulation of DNA damage and impaired regenerative capacity. Heterochronic parabiosis experiments, in which the circulatory systems of young and old mice are joined, have demonstrated that the blood of young animals contains factors that can improve stem cell function in many organs. Three studies examine the molecular, cellular, and functional changes that the infusion of blood from young mice induces in the muscles and brains of aged mice. Sinha et al. report that heterochronic parabiosis improved muscle function, decreased genomic damage in muscle stem cells, and increased the physical strength and stamina of aged mice. Similarly, Katsimpardi et al. report that heterochronic parabiosis stimulated vascular remodeling and increased blood flow in the cerebrum, promoted the proliferation of neural stem cells that give rise to olfactory neurons, and improved olfaction in aged mice. In these studies, treating aged mice with recombinant GDF11 (growth differentiation factor 11), which is abundant in young mice and decreases with age, recapitulated the effects of heterochronic parabiosis. In another study, Villeda et al. report that the benefits of young blood extend to cognition. Aged mice parabiotically paired with young mice exhibited improved learning and memory and greater hippocampal synaptic plasticity. These changes required activation of the transcription factor Creb (cyclic adenosine monophosphate response element-binding protein), which has been previously implicated in synaptic plasticity. These studies may not have identified the fountain of youth, but they suggest potential mechanisms for restoring the regenerative capacity of stem cells to enhance physical strength and increasing synaptic plasticity to improve cognitive functions in aged individuals.

M. Sinha, Y. C. Jang, J. Oh, D. Khong, E. Y. Wu, R. Manohar, C. Miller, S. G. Regalado, F. S. Loffredo, J. R. Pancoast, M. F. Hirshman, J. Lebowitz, J. L. Shadrach, M. Cerletti, M.-J. Kim, T. Serwold, L. J. Goodyear, B. Rosner, R. T. Lee, A. J. Wagers, Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle. Science 344, 649–652 (2014). [Abstract] [Full Text]

L. Katsimpardi, N. K. Litterman, P. A. Schein, C. M. Miller, F. S. Loffredo, G. R. Wojtkiewicz, J. W. Chen, R. T. Lee, A. J. Wagers, L. L. Rubin, Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science 344, 630–634 (2014). [Abstract] [Full Text]

S. A. Villeda, K. E. Plambeck, J. Middeldorp, J. M. Castellano, K. I. Mosher, J. Luo, L. K. Smith, G. Bieri, K. Lin, D. Berdnik, R. Wabl, J. Udeochu, E. G. Wheatley, B. Zou, D. A. Simmons, X. S. Xie, F. M. Longo, T. Wyss-Coray, Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat. Med.; published online 4 May 2014; DOI:10.1038/nm.3569. [PubMed]