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A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status.

Sood S, Gallagher IJ, Lunnon K, Rullman E, Keohane A, Crossland H, Phillips BE, Cederholm T, Jensen T, van Loon LJ, Lannfelt L, Kraus WE, Atherton PJ, Howard R, Gustafsson T, Hodges A, Timmons JA - Genome Biol. (2015)

Bottom Line: Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity.We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample.This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.

View Article: PubMed Central - PubMed

Affiliation: XRGenomics Ltd, London, UK.

ABSTRACT

Background: Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health.

Results: One hundred and fifty probe-sets form an accurate classifier of young versus older muscle tissue and this healthy ageing RNA classifier performed consistently in independent cohorts of human muscle, skin and brain tissue (n = 594, AUC = 0.83-0.96) and thus represents a biomarker for biological age. Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity. The gene score is 'up-regulated' in healthy human hippocampus with age, and when applied to blood RNA profiles from two large independent age-matched dementia case-control data sets (n = 717) the healthy controls have significantly greater gene scores than those with cognitive impairment. Alone, or when combined with our previously described prototype Alzheimer disease (AD) RNA 'disease signature', the healthy ageing RNA classifier is diagnostic for AD.

Conclusions: We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample. This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.

No MeSH data available.


Related in: MedlinePlus

Validation of novel blood RNA classifiers as a diagnostic for Alzheimer’s disease. We used the independent batch 2 AD data set (see “Materials and methods”) to test the predictive performance of our healthy ageing classifier and our previously published AD prototype diagnostic. The performance of each was evaluated using ROC curves. The healthy ageing gene classifier generated independent AUCs of 0.73 and 0.66 for AD in cohorts 1 and 2, respectively. For the combined ‘healthy ageing’ plus ‘AD disease’ RNA classifier (150 + 48 probe-sets) we obtained AUCs of 0.86 and 0.73 for AD without any attempt at optimization. The AD disease RNA classifier probe-sets were selected using cohort 1
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Fig5: Validation of novel blood RNA classifiers as a diagnostic for Alzheimer’s disease. We used the independent batch 2 AD data set (see “Materials and methods”) to test the predictive performance of our healthy ageing classifier and our previously published AD prototype diagnostic. The performance of each was evaluated using ROC curves. The healthy ageing gene classifier generated independent AUCs of 0.73 and 0.66 for AD in cohorts 1 and 2, respectively. For the combined ‘healthy ageing’ plus ‘AD disease’ RNA classifier (150 + 48 probe-sets) we obtained AUCs of 0.86 and 0.73 for AD without any attempt at optimization. The AD disease RNA classifier probe-sets were selected using cohort 1

Mentions: Clinical characteristics of batch 1 and batch 2 of case–control subjects that contributed to the blood gene-chip profiles analyzed and presented in Figs. 4 and 5


A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status.

Sood S, Gallagher IJ, Lunnon K, Rullman E, Keohane A, Crossland H, Phillips BE, Cederholm T, Jensen T, van Loon LJ, Lannfelt L, Kraus WE, Atherton PJ, Howard R, Gustafsson T, Hodges A, Timmons JA - Genome Biol. (2015)

Validation of novel blood RNA classifiers as a diagnostic for Alzheimer’s disease. We used the independent batch 2 AD data set (see “Materials and methods”) to test the predictive performance of our healthy ageing classifier and our previously published AD prototype diagnostic. The performance of each was evaluated using ROC curves. The healthy ageing gene classifier generated independent AUCs of 0.73 and 0.66 for AD in cohorts 1 and 2, respectively. For the combined ‘healthy ageing’ plus ‘AD disease’ RNA classifier (150 + 48 probe-sets) we obtained AUCs of 0.86 and 0.73 for AD without any attempt at optimization. The AD disease RNA classifier probe-sets were selected using cohort 1
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4561473&req=5

Fig5: Validation of novel blood RNA classifiers as a diagnostic for Alzheimer’s disease. We used the independent batch 2 AD data set (see “Materials and methods”) to test the predictive performance of our healthy ageing classifier and our previously published AD prototype diagnostic. The performance of each was evaluated using ROC curves. The healthy ageing gene classifier generated independent AUCs of 0.73 and 0.66 for AD in cohorts 1 and 2, respectively. For the combined ‘healthy ageing’ plus ‘AD disease’ RNA classifier (150 + 48 probe-sets) we obtained AUCs of 0.86 and 0.73 for AD without any attempt at optimization. The AD disease RNA classifier probe-sets were selected using cohort 1
Mentions: Clinical characteristics of batch 1 and batch 2 of case–control subjects that contributed to the blood gene-chip profiles analyzed and presented in Figs. 4 and 5

Bottom Line: Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity.We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample.This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.

View Article: PubMed Central - PubMed

Affiliation: XRGenomics Ltd, London, UK.

ABSTRACT

Background: Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health.

Results: One hundred and fifty probe-sets form an accurate classifier of young versus older muscle tissue and this healthy ageing RNA classifier performed consistently in independent cohorts of human muscle, skin and brain tissue (n = 594, AUC = 0.83-0.96) and thus represents a biomarker for biological age. Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity. The gene score is 'up-regulated' in healthy human hippocampus with age, and when applied to blood RNA profiles from two large independent age-matched dementia case-control data sets (n = 717) the healthy controls have significantly greater gene scores than those with cognitive impairment. Alone, or when combined with our previously described prototype Alzheimer disease (AD) RNA 'disease signature', the healthy ageing RNA classifier is diagnostic for AD.

Conclusions: We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample. This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.

No MeSH data available.


Related in: MedlinePlus