rRNA-gene methylation and biological aging

Epigenetic modifications, which are programmed across the individual’s lifespan by the genetic background but also modulated by environmental and lifestyle factors, are widely studied to identify biomarkers of human aging. Indeed, Garagnani et al. identified three genes whose methylation level strongly correlates with age [1]. Subsequently, Horvarth defined a high precise DNA methylation clock, able to predict age, with a low margin of error, based on methylation levels of a series of CpG sites scattered throughout the genome. These markers, and others which have consequently been identified, have proved to be reliable enough to be used for forensic purposes in order to define the age of human subjects by analysing these markers in different specimens (such as teeth, blood, semen) [2]. On the other hand, most of the scientists involved with research on aging are willing to identify epigenetic modifications correlated with biological rather than with chronological age. Such markers may be important firstly because the definition of biological age in the elderly may be much more useful than chronological age to identify the subjects needing (medical or social) care; secondly, because the identification of genes the methylation of which is correlated with biological aging may give important clues on the aging process and, possibly, on how to modulate it. Many hints suggest that these markers are likely to exist. For instance, global methylation showed to be correlated with biological and not with chronological age [3]. Ribosomal RNA (rRNA) genes consist of highly evolutionary conserved tandem and clusters of units within nucleolar organizer regions, distributed, in humans, on the short arms of acrocentric chromosomes. The expression of rRNA genes is regulated during different stages of lifetime by several factors, including nutrients, transcription factors and epigenetic marks as well [4, 5]. Previous studies have indicated that alterations of rRNA expression may be related to specific pathological conditions, such as different types of cancers and Alzheimer Disease [6]. In addition, the analysis of fibroblasts from patients with Werner Syndrome, and of hematopoietic cells from rats of different ages suggested a correlation with physiological and pathological aging. These data, coupled with the acknowledged importance of protein use and storage in the elderly, attracted our interest, suggesting that the expression of rRNA genes may be correlated to the functional status of old subjects Editorial