More Work on Gene Expression Changes as a Biomarker of Aging

A range of research groups are presently working on the development of biomarkers based on gene expression changes that occur with aging. Insofar as everyone suffers the same forms of cell and tissue damage that causes aging, it should be expected that cellular reactions to rising levels of that damage have similar patterns, albeit mixed in with environment effects and individual differences. A robust biomarker of aging would be a very useful thing to have to hand, as without it the only way to prove that a potential rejuvenation therapy in fact extends healthy life is to wait and see. That is slow and expensive, even in mouse studies, and this cost is a ball and chain holding back the pace of progress.

Researchers examined expression of genes in blood samples from 15,000 people across the world. They found 1,450 genes that are linked to ageing, and also uncovered a link between these genes and factors such as diet, smoking and exercise. The research team specifically looked for changes in gene expression, a process in which the information contained in genes is 'expressed' by reading the DNA sequence and creating RNA, and subsequently proteins. By looking in blood, the researchers aimed to find easy to measure markers of human ageing. This technique allowed them to develop a new method to predict people's 'biological age' and show that people with a biological age older than their actual age were more likely to have conditions such as high blood pressure or cholesterol. Many of the genes work together in pathways such as generating the energy supply of the cells (mitochondrial function), metabolic processes, and the stability and flexibility of the cells.

"This study has discovered many genes that change in their patterns of expression with age. This study has not only given insights into ageing mechanisms - such as mitochondrial function - but these techniques have potential use in prediction and treatment. Large, observational, and collaborative projects such as these provide a great platform to focus ageing research in the future, with the hope that predictive tests can be developed, and treatment strategies for age-related conditions improved."

Link: http://www.exeter.ac.uk/news/featurednews/title_478415_en.html

Comments

Great, the better the biomarkers we have the easier to prove efficacy without waiting till people die. One of the best sets of biomarkers is the system Steve Horvath uses at UCLA, he offers free software to interpret DNAm data from Ilumina 450k assays that offer very accurate biomarkers for aging so the more tools we have to join that the better!

Posted by: Steve H at October 26th, 2015 11:17 AM

The results of this study are not only important as biomarkers!

In line with both the SENS approach and the viewpoint of programmed aging, we should correct the gene expression levels to a youthfull state!

Posted by: Prometheus at October 26th, 2015 5:19 PM

Sens does not tinker with metabolism to restore youthful gene expression. They seem more interested in replacing things like dysfunctional telomeres and aged stem cells rather than messing with metabolism.

Posted by: Steve h at October 26th, 2015 5:25 PM

Hello everyone!

This study is great and indeed the finer we comprehend, differentiate, identify and classify the details and differences between transcriptional aging, epigenetic aging, chronological aging and pathological (with diseases) aging by creating new truly reliable biological markers; the better our capacity to create and adapt new (non-) genetic therapies to various states of aging. The devil is in the details or is it the perfection (quest) ?

Quote of full study's very important take-away point (phenotypes) :

" A positive delta age, interpreted as reflecting *more rapid biological ageing*, was *consistently*
associated with higher systolic blood pressure and diastolic blood pressure, total cholesterol, HDL cholesterol [and we can hypothesize higher LDL too, it wasn't measured. LDL major culprit of atherosclerotic plaque formation], *fasting glucose* [this one IMHO is the most important one to correlate with true longevity, be it transcriptional and/or epigenetic aging. Glycemic homeostasis is crucial to avoid accelerated AGEs ECM glycation/crosslink formation (hello glucosepane) like in diabetes with rising fasting glucose levels and dysfunctional pancreatic beta cells] and body-mass-index (BMI) [that one two is highly revealing though it is not perfect predictor. Some centenarians were fat obese people with high BMI in their 5th decade and later on slowly reduced BMI to live 100
]. "

Posted by: CANanonymity at October 27th, 2015 12:20 PM

Part 2

I wish to stress fasting blood glucose FBG because, " in these metformin times ", it has immense significance. The longest-lived mammals keep FBG in check, otherwise they prematurely die from accelerated AGEs glycation aging (diabetes). Advanced Glycation End-products (AGEs) have direct correlation to specie maximal longevity (just check mouse ECM collagen glycation rate by Pentosidine or CML formation, mice accumulate Pentosidine 40 times faster than in human ECM. They die 40 times faster too, a strong correlation to MLSP). Not just some random 'convenient' coincidental correlation when it suits the researcher's study (biased) results,
but a in vivo provable *Causation* of biological aging (including transcriptional and epigenetic aging types).
Indeed, this next study (see link below) shows how FBG and PPBG (post-prandial) are a big part of the AGEs puzzle/equation. The fact that feeding high-AGE concentrated food in calorie restricted mice despite lower quantitative amount of food given (calorie wise and carbs wise (amount/type carbohydrates large culprit of FBG and PPBG) led to - Shorter lifespans (nullified calorie restriction effect). Whereas, the other mice on 'all you can eat - but only nutritious low-AGE food', who ate more calories lived - Longer lifespans than the CR mice eating only damaging/unutritious high-AGE
food. AGEs load intake were the culprit - not calories or carbs. AGEs = MLSP.

1. http://www.ncbi.nlm.nih.gov/pubmed/17525257

Posted by: CANanonymity at October 27th, 2015 1:21 PM

Erratum : link 4. doesn't work, and actually link 2, the study is two old CR fed mice groups, both are CR mice, one fed high AGEs and the other low AGEs concentrated food, my apologies. Still, high AGE food accelerated the mice's aging, thus carbs/calories do still have a certain impact fot they are converted to the culprit (AGEs) during glycation process.

Posted by: CANanonymity at October 27th, 2015 2:34 PM

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