Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice

Abstract

As human lifespan increases, a greater fraction of the population is suffering from age-related cognitive impairments, making it important to elucidate a means to combat the effects of aging1,2. Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level. Genome-wide microarray analysis of heterochronic parabionts—in which circulatory systems of young and aged animals are connected—identified synaptic plasticity–related transcriptional changes in the hippocampus of aged mice. Dendritic spine density of mature neurons increased and synaptic plasticity improved in the hippocampus of aged heterochronic parabionts. At the cognitive level, systemic administration of young blood plasma into aged mice improved age-related cognitive impairments in both contextual fear conditioning and spatial learning and memory. Structural and cognitive enhancements elicited by exposure to young blood are mediated, in part, by activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus. Our data indicate that exposure of aged mice to young blood late in life is capable of rejuvenating synaptic plasticity and improving cognitive function.

Extracellular RNA profiles with human age

“…Accumulating evidence suggests that circulating factors play important roles in regulating tissue function and aging. Studies demonstrate that old mice exposed to blood from young mice improved cognitive and muscle function and had less‐evident brain atrophy (Conboy et al., 2005; Katsimpardi et al., 2014; Villeda et al., 2014). The circulating molecules that mediate this effect are yet to be elucidated.…”

Aging hair follicles rejuvenated by transplantation to a young subcutaneous environment

“…Recently, parabiosis experiments pairing old and young mice have suggested that some features of aging organs in old mice, in particular stem cells, can be reversed by factors in blood of young mice, 1 including brain, 2,3 spinal cord, 4 and heart. 5 The hair follicle, which cycles through telogen (resting), anagen (growing), and catagen (regression) throughout the life of mammals, undergoes obvious age-related changes including hair loss.…”

“…Instead of using complex parabiosis surgery, 3 we used hairfollicle subcutaneous transplantation in order to determine if the hair follicle, including its ability to produce hair shafts, and its HAP stem cells, can be rejuvinated.…”

An ingredient for the elixir of youth

“…This procedure can rejuvenate a number of organs in the older of the pair [1][2][3]. The provision of young blood even enhances cognitive performance in aged mice by improving synaptic plasticity in the hippocampus [4]. Conversely, aged blood has negative effects on the brain and skeletal muscle of young animals [5,6].…”