N6-methyladenosine RNA methylation is modulated in aging and age-related diseases

Alterations in the epigenetic transcriptome are crucial in the aging process and the occurrence of age-related diseases. This study aims to define global RNA methylation patterns in nursing home residents, an aged population with a high burden of age-related health deficits and sharing a common environment. The study was conducted on RNA samples extracted from blood samples of 56 older adults in a nursing home and of 36 young subjects living independently in their own homes. The RNA samples were both used for the quantification of the global methylation levels by ELISA assays and for the evaluation of the gene expression of enzymes specifically involved in RNA methylation/demethylation reactions as well as in decoding the m6A epigenetic message by comparative-relative qPCR. In older adults , lower m6A RNA levels compared to the younger subjects and a correlation between m6A levels, and the Geriatric Depression Scale were observed. Consistently, a generalized reduction in the expression of the writer, reader, and eraser genes emerged, both in older adults compared to younger ones and in the presence of a poor health status and pathological conditions such as diabetes and heart disease. Overall, data reveal that a consistent process of demethylation of the transcriptome via the downregulation of the expression of genes involved in m6A RNA methylation occurs, late in life, depending on the overall health status of the population sample. Further studies are needed to clarify whether this process is representative of old age and/or age-related phenotypes or is rather population specific. This will provide useful insights for improving nursing care, well-being, and healthy aging. • m6A RNA levels are decreased in older adults compared to younger ones. • A reduced expression of genes involved in m6A RNA methylation process occurs, late in life, depending on the overall health status of the population sample. • Understanding the epigenetic plasticity of RNA patterns in aging and age-related disease is crucial for improving overall health and quality of life.