Abstract
Aging is a key risk factor for chronic diseases of the elderly. MicroRNAs regulate post-transcriptional gene silencing through base-pair binding on their target mRNAs. We identified nonlinear changes in age-related microRNAs by analyzing whole blood from 1334 healthy individuals. We observed a larger influence of the age as compared to the sex and provide evidence for a shift to the 5’ mature form of miRNAs in healthy aging. The addition of 3059 diseased patients uncovered pan-disease and disease-specific alterations in aging profiles. Disease biomarker sets for all diseases were different between young and old patients. Computational deconvolution of whole-blood miRNAs into blood cell types suggests that cell intrinsic gene expression changes may impart greater significance than cell abundance changes to the whole blood miRNA profile. Altogether, these data provide a foundation for understanding the relationship between healthy aging and disease, and for the development of age-specific disease biomarkers.
Highlights
Aging is a key risk factor for chronic diseases of the elderly
We previously reported a significant number of age-related miRNAs26, and Huan and coworkers measured a selection of miRNAs by RT-qPCR in whole blood from over 5000 individuals from the Framingham Heart Study[27]
As males have shorter lifespans than females, and each sex suffers a different array of agerelated diseases, we investigated the interplay between age and sex on blood miRNA profiles
Summary
Aging is a key risk factor for chronic diseases of the elderly. MicroRNAs regulate posttranscriptional gene silencing through base-pair binding on their target mRNAs. Computational deconvolution of whole-blood miRNAs into blood cell types suggests that cell intrinsic gene expression changes may impart greater significance than cell abundance changes to the whole blood miRNA profile These data provide a foundation for understanding the relationship between healthy aging and disease, and for the development of age-specific disease biomarkers. Functional improvement of aged tissues has been achieved by an expanding number of techniques, ranging from dietary restriction[9] to senescent cell elimination and partial cellular reprogramming. This includes heterochronic parabiosis, in which an old mouse is exposed to a young circulatory system. That each plasma protein interacts with complex intracellular regulatory networks, and that alterations to such networks are a key component of aging and rejuvenation
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