7 replies to this topic

[xEva]

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.

from the discussion section:

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.

[MikeDC]

We don't know if it is programmed or natural deterioration in the brain that is causing it. There is another paper that showed microRNAs secretion determine aging speed. If we can figure out all the microRNAs require at the youthful level. We can do periodic infusions.

[xEva]

So you're saying that the well-known events like synaptic pruning, the first phase of which has long been known to occur just before puberty, is not part of the programmed development but "natural deterioration" -?

 

In epigenetic shifts of gene expression, what can distinguish the two?  (i.e. programmed development vs natural deterioration) 

 

Re RNAs, micro and otherwise, sure they can affect gene expression, but aren't they, firstly, the product of the active genes?

[MikeDC]

Synaptic pruning ends just before puberty and starts again in adulthood.
Human development and aging is chain reaction. Not time based programming

[tunt01]

 

Re RNAs, micro and otherwise, sure they can affect gene expression, but aren't they, firstly, the product of the active genes?

 

Yes.  miRNA are 19-24 bps and encoded from active genes and cut/processed (Drosha/Dicer-dependent).  

 

See this graphic and the associated paper from Wang, et al.

 

 

 

Wang J, e. (2017). Nutrition, epigenetics, and metabolic syndrome. - PubMed - NCBI. Ncbi.nlm.nih.gov. Retrieved 17 September 2017, from https://www.ncbi.nlm...pubmed/22044276

[RWhigham]

The fountain of youth operating in heterochronic parabiosis may be differences in thousands microRNAs, so the search for a magic molecule is not going to work. These differences are directed by an aging clock in the hypothalamus gland. See Josh Mitteldorf

[MikeDC]

Nobody is searching for a single molecule. We are searching for important molecules that have major impact on aging. NAD+ is probably the first one we have found and we happen to have a solution already with NR. Klotho is also a major one, but we don’t have a good solution to increase it. Temporary solution is to use GABA which can restore Klotho levels for old people. The other important factor is senolytics. Let’s hope FOXO4-DRI prove effective in humans.

[abelard lindsay]

This epigenetic theory of aging is the idea behind the Russian anti-aging peptides.  They extract low molecular weight peptides from young cow organs and put those in pills.  The theory is that the peptides epigenetically alter the DNA expression in cells making them act like younger cells.  That the epigenetic signaling is conserved across mammalian species is unlikely, but not impossible. 

 

I agree that this is not going to end in a single molecule.  Though one of them  might be synthetic GHRH or similar as these are produced within the hypothalmus.  That would certainly be a good place to look for the human epigenetic clock.

Edited by abelard lindsay, 25 March 2018 - 06:09 AM.