A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia, 2017
from the abstract:
We found that lifespan transcriptome trajectories describe a calendar of gene regulatory events in the brain of humans and mice. Transcriptome trajectories defined a sequence of gene expression changes in neuronal, glial and endothelial cell-types, which enabled prediction of age from tissue samples.
...
We propose a genomic program generates a lifespan calendar of gene regulation that times age-dependent molecular organization of the brain and mutations that interrupt the program in young adults cause schizophrenia.
We focussed on identifying age-dependent gene regulatory events that were detected when the trajectory in the level of gene expression changed. Studying the transcriptome trajectories across the lifespan of the human neocortex and mouse hippocampus showed that TTTPs occurred at all ages. Moreover, because these events were a defining characteristic of every age, we found that actual age could be predicted by examination of an RNA sample from mouse and human brain tissue. These findings indicate there is a ‘genetic lifespan calendar’ that sets the date for gene expression changes in both species.
we conclude that mammals with greatly differing lifespans share a conserved genomic program regulating the sequence of cellular and synaptic changes throughout the lifespan.
Even though there are major changes during brain maturation in young adults, the complex trajectories were found throughout the lifespan, suggesting they could be used to predict the biological age of the brain. To test this, we used radial basis support vector machines and demonstrated that classifiers trained on partitioned subsets of the gene expression data (training sets) predicted age in the test sets with an accuracy ... in humans of 5.5 years and 28 days in mice. Remarkably, they showed accurate age predictions across the entire range of ages in both species (human, R2 = 0.88, mice, R2 = 0.94) using only 40 probes in humans and 100 in mice. Thus, TTTPs and trajectories are highly characteristic features defining brain age across the lifespan in mice and humans. This indicates a ‘genetic lifespan calendar’ of transcriptome events is a conserved feature of mammals.
So, who'll be the first to poo-poo it?
Edited by xEva, 17 September 2017 - 01:27 AM.