10 ms·

Biomarkers and ageing: The clock-watcher

58 points by moyix 13y ago

danieltillett 13y ago
This is an amazing result. I can understand why he had so much problems in getting this published - it really does sound too good to be true. If it does hold up (and it looks pretty good so far) this truly is a nobel prize winning discovery. What having a good age clock of this accuracy allows is the practicable development of age slowing pharmaceuticals that can be shown to work in humans. This is exactly the sort of biotech area that YC should be supporting. Here is the original paper http://genomebiology.com/2013/14/10/R115 http://genomebiology.com/2013/14/10/R115
danieltillett 13y ago
For those without background in genetics the FAQ page of the paper author (Steve Horvath) is worth readings as it is a bit easier to understand than the main paper [0]. For those that think this is still tl;dr he has posted the following summary there: What is new in the article? Where is the beef? The epigenetic clock is the first age prediction method based on DNAm levels that accurately predicts age in more than one tissue or fluid. As a matter of fact, it works in the vast majority of tissues/fluids/organs. It is arguably the first accurate measure of age that allows one to compare the ages of different parts of the human body. Researchers who develop genomic biomarkers will appreciate its astonishing accuracy, the fact that it works across two Illumina array platforms and that it is remarkably robust to batch effects. The epigenetic clock yields many interesting insights. Here is a top 10 list: 1) stem cells and iPS cells are perfectly young, 2) the epigenetic clock works in chimpanzees, 3) age acceleration effects (measured by the clock) are highly heritable, 4) normal female breast tissue (adjacent to tumor) exhibits positive age acceleration effects while heart tissue appears younger, 5) cell passaging increases DNAm age, 6) the ticking rate of the epigenetic clock is fastest during development, 7) tumor morphology does not relate to age acceleration, 8) there is a weak inverse relationship between the number of somatic mutations and age acceleration in many cancer types, 9) mutations in steroid receptors are associated with lower age acceleration effects in breast cancer tissue, 10) TP53 mutation status relates to age acceleration. The big picture: Most (but certainly not all) prior articles propose that age effects on DNA methylation levels represent noise or epigenetic drift, see for example the excellent recent article by A. Teschendorff et al (2013). Hum Mol Genet. PMID: 23918660. While epigenetic drift may explain age related changes for most CpGs, Horvath (2013) presents compelling data that the epigenetic clock relates to a purposeful biological process. Further, it proposes the epigenomic maintenance system (EMS) model of DNAm age. [0] http://labs.genetics.ucla.edu/horvath/htdocs/dnamage/faq.htm http://labs.genetics.ucla.edu/horvath/htdocs/dnamage/faq.htm
cliveowen 13y ago
This man is pure genius.
untilHellbanned 13y ago
I like how this paper is a major breakthrough and is not published in Nature but is reported on in Nature. Hopefully Prof. Horvath will get the recognition he deserves.
coldcode 13y ago
Fascinating work. Makes me wish I had gotten my PhD when I had the chance so I could work on stuff like this.

58 points by moyix 13y ago

This is an amazing result. I can understand why he had so much problems in getting this published - it really does sound too good to be true. If it does hold up (and it looks pretty good so far) this truly is a nobel prize winning discovery. What having a good age clock of this accuracy allows is the practicable development of age slowing pharmaceuticals that can be shown to work in humans. This is exactly the sort of biotech area that YC should be supporting. Here is the original paper http://genomebiology.com/2013/14/10/R115 http://genomebiology.com/2013/14/10/R115

danieltillett 13y ago

For those without background in genetics the FAQ page of the paper author (Steve Horvath) is worth readings as it is a bit easier to understand than the main paper [0]. For those that think this is still tl;dr he has posted the following summary there: What is new in the article? Where is the beef? The epigenetic clock is the first age prediction method based on DNAm levels that accurately predicts age in more than one tissue or fluid. As a matter of fact, it works in the vast majority of tissues/fluids/organs. It is arguably the first accurate measure of age that allows one to compare the ages of different parts of the human body. Researchers who develop genomic biomarkers will appreciate its astonishing accuracy, the fact that it works across two Illumina array platforms and that it is remarkably robust to batch effects. The epigenetic clock yields many interesting insights. Here is a top 10 list: 1) stem cells and iPS cells are perfectly young, 2) the epigenetic clock works in chimpanzees, 3) age acceleration effects (measured by the clock) are highly heritable, 4) normal female breast tissue (adjacent to tumor) exhibits positive age acceleration effects while heart tissue appears younger, 5) cell passaging increases DNAm age, 6) the ticking rate of the epigenetic clock is fastest during development, 7) tumor morphology does not relate to age acceleration, 8) there is a weak inverse relationship between the number of somatic mutations and age acceleration in many cancer types, 9) mutations in steroid receptors are associated with lower age acceleration effects in breast cancer tissue, 10) TP53 mutation status relates to age acceleration. The big picture: Most (but certainly not all) prior articles propose that age effects on DNA methylation levels represent noise or epigenetic drift, see for example the excellent recent article by A. Teschendorff et al (2013). Hum Mol Genet. PMID: 23918660. While epigenetic drift may explain age related changes for most CpGs, Horvath (2013) presents compelling data that the epigenetic clock relates to a purposeful biological process. Further, it proposes the epigenomic maintenance system (EMS) model of DNAm age. [0] http://labs.genetics.ucla.edu/horvath/htdocs/dnamage/faq.htm http://labs.genetics.ucla.edu/horvath/htdocs/dnamage/faq.htm

cliveowen 13y ago

This man is pure genius.

untilHellbanned 13y ago

I like how this paper is a major breakthrough and is not published in Nature but is reported on in Nature. Hopefully Prof. Horvath will get the recognition he deserves.

coldcode 13y ago

Fascinating work. Makes me wish I had gotten my PhD when I had the chance so I could work on stuff like this.