Brain Ageing: Blood-Derived Rejuvenation

RESEARCH HIGHLIGHTS

Je n n ie V a l l BRAIN AGEING i s / N

P Blood-derived rejuvenation G Studies have shown that blood from effects of young plasma. This suggests muscle — increased young mice, when introduced into that increased CREB1 signalling in blood vessel volume old animals, counteracts ageing- part mediates the effect of young and SVZ stem cell related effects in various tissues, plasma on hippocampus-dependent number in old mice, including the brain. Building on these cognitive function in old mice. suggesting that findings, three new studies show that Brain ageing is also associated GDF11‑induced young blood improves brain and with decreased adult neurogenesis, vasculature remod- muscle function in aged mice, and possibly resulting from a reduction in elling may at least provide insight into the mechanisms the number of adult neural stem cells, in part mediate underlying these effects. and a previous study showed that old the increased adult Wyss-Coray and colleagues heterochronic parabionic mice gener- neurogenesis and examined the effects of young blood ated more neurons in the subgranular olfactory function on the hippocampus (which shows zone of the DG, a region of adult in old heterochronic parabionts. ageing-related functional decline) in neurogenesis, than old isochronic The ability of GDF11 to reverse part by surgically joining the circula- parabionts. ageing-associated tissue dysfunction tory systems of two mice (a technique Rubin and colleagues found that was further highlighted by a recent called parabiosis). old heterochronic parabionic mice study on muscle cells. Aged muscle Compared with old isochronic have increased numbers of neural exhibits a decrease in the number parabionts (old mice that had been stem cells in the subventricular and function of muscle stem cells, surgically connected to other old zone (SVZ) of the lateral ventricles, and Wagers and colleagues showed mice), old heterochronic parabionts another site of adult neurogenesis. that treatment of aged mice with (old mice that had been surgically Neuroblasts derived from SVZ-born recombinant GDF11 increased connected to young mice) exhibited stem cells migrate to the olfactory the number of these cells and their increased expression of immediate- bulb, and bromodeoxyuridine stain- activity in regeneration assays, and early genes in dentate gyrus (DG) ing revealed that old heterochronic enhanced muscle function (as meas- cells and a rise in phosphorylated parabionts had nearly double the ured by grip strength and endurance CREB1 (cyclic AMP-responsive number of newborn olfactory exercise paradigms). element-binding protein 1) in the DG neurons than did old isochronic Together, these studies provide and CA1 — findings consistent with parabionts. Interestingly, old hetero- further evidence for the potentially increased synaptic plasticity. Indeed, chronic parabionts performed better rejuvenating effects of young blood hippocampal slice recordings showed in an odour discrimination task, on ageing tissues. Specifically, they Together, enhanced long-term potentiation suggesting that exposure to young reveal two different potential path- in the DG of old heterochronic blood improves olfactory function ways by which circulatory factors these studies parabionts. in aged mice by promoting SVZ may restore function in aged brains. provide further In agreement with these findings, neurogenesis. Darran Yates evidence for old mice that received repeated injec- Three-dimensional reconstruc- the potentially tions of plasma from young animals tions of brain vasculature revealed ORIGINAL RESEARCH PAPERS Villeda, S. A. exhibited increased learning and that old heterochronic parabionts et al. Young blood reverses age-related rejuvenating impairments in cognitive function and synaptic memory in hippocampus-dependent had greater blood vessel volume in plasticity in mice. Nature Med. http://dx.doi. effects of behavioural tasks compared with old the SVZ and other regions than old org/10.1038/nm.3569 (2014) | Katsimpardi, L. et al. young blood mice that received injections of old isochronic parabionts. Moreover, daily Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science on ageing plasma. Interestingly, expressing a injections of growth/differentiation 344, 630–634 (2014) | Sinha, M. et al. Restoring dominant-negative form of CREB1 factor 11 (GDF11) — which is found systemic GDF11 levels reverses age-related tissues into the DG of old mice partially in serum and known to counteract dysfunction in mouse skeletal muscle. Science 344, 649–652 (2014) reduced the cognitive-enhancing ageing-related effects on cardiac

NATURE REVIEWS | NEUROSCIENCE VOLUME 15 | JUNE 2014