 The healthy ageing RNA signature in healthy human brain tissue and blood of AD patients and controls. There was robust regulation of the healthy ageing RNA signature in human brain with healthy ageing and between control subjects and subjects with AD or MCI. The healthy ageing RNA signature in healthy human brain tissue and blood of AD patients and controls. There was robust regulation of the healthy ageing RNA signature in human brain with healthy ageing and between control subjects and subjects with AD or MCI. a The healthy ageing RNA signature was studied across brain regions in healthy individuals using BrainEac.org gene-chip resource [GEO:GSE60862]. Ten brain regions from 134 subjects representing 1231 samples were individually ranked (see “Materials and methods”) and the median sum of the ranked scores calculated. Regulation of the healthy ageing genes differed across brain regions with age, as determined by a Kruskal Wallis Test (hippocampus p = 0.00000002, putamen p = 0.00000004, thalamus p = 0.00004, temporal cortex p = 0.0001, substantia nigra p = 0.0002, frontal cortex p = 0.001, occipital cortex p = 0.001, white matter p = 0.01, medulla p = 0.06 and cerebellar cortex p= 0.51). Post hoc Mann–Whitney test, with correction for multiple comparisons (Holm), confirmed a striking ‘increase’ of the healthy ageing score in the healthy older samples (hippocampus, putamen, thalamus, substantia nigra, and the occipital, frontal, and temporal cortex regions; at least p < 0.002). b The healthy ageing RNA signature was studied in blood samples from two independently processed case–control studies of AD. In cohort 1 the control median gene score was greater (p = 0.004) than AD samples and greater (p = 0.00005) than that of the MCI samples (Wilcoxon rank sum test). In cohort 2 the median gene score of control samples was greater than that of AD samples (p = 0.009) and that of MCI samples (p = 0.003). Data are median gene score and standard error
Sood et al. Genome Biology 2015 16:185 doi:10.1186/s13059-015-0750-x |
A ‘gene signature’ that could be used to predict the onset of diseases, such as Alzheimer’s, years in advance has been developed by scientists. The study aimed to define a set of genes associated with ‘healthy aging’ in 65 year olds. Such a molecular profile could be useful for distinguishing people at earlier risk of age-related diseases.
“We use birth year, or chronological age, to judge everything from insurance premiums to whether you get a medical procedure or not. Most people accept that all 60 year olds are not the same, but there has been no reliable test for underlying ‘biological age’, said James Timmons, from King’s College London.
“Our discovery provides the 1st robust molecular ‘signature’ of biological age in humans and should be able to transform the way that ‘age’ is used to make medical decisions. This includes identifying those more likely to be at risk of Alzheimer’s, as catching those at ‘early’ risk is key to evaluating potential treatments.”
METHOD: The researchers analyzed the RNA of healthy 65yo subjects, and used the information to develop a signature of 150 RNA genes that indicated ‘healthy aging’. The signature was found to be a reliable predictor for risk of age-related disease when studying RNA from tissues including human muscle, brain and skin. With this RNA signature, they developed a ‘healthy age gene score’ which they used to test and compare the RNA profiles of different individuals, and demonstrated that a greater score was associated with better health in men and women.
They studied RNA from healthy 70 year old subjects and analyzed follow-up health data over 2 decades. Despite all subjects being born within a year of each other, their RNA at around 70yo showed a very wide distribution in ‘healthy age gene score’, varying over a 4-fold range. This variation was shown to link to long term health. A greater gene score was also associated with better cognitive health and renal function across a 12 year span – both important determinants of mortality.
In particular, patients diagnosed with Alzheimer’s Disease had an altered ‘healthy aging’ RNA signature in their blood, and thus lower healthy age gene score, suggesting significant association with the disease.
Timmons added: “This is the first blood test of its kind that has shown that the same set of molecules are regulated in both the blood and the brain regions associated with dementia, and it can help contribute to a dementia diagnosis. This also provides strong evidence that dementia could be called a type of ‘accelerated aging’ or ‘failure to activate the healthy aging program’.”
Given that early intervention is important in Alzheimer’s and there is a need to identify those at greatest risk, ‘healthy age gene score’ could be integrated to help decide which middle-aged subjects could be offered entry into a preventative clinical trial many years before the clinical expression of Alzheimer’s. http://www.genomebiology.com/2015/16/1/185 http://www.eurekalert.org/pub_releases/2015-09/bc-ewg090315.php
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