The Open Geriatric Medicine Journal, 2011, 4, 1-5 1 1874-8279/11 2011 Bentham Open Open Access Ribosomal Genes Activity in Aged Down Syndrome Subjects Alaíde Gonçalves, Yara Regina Bianchini Ávalos, Elizabeth Suchi Chen, Bianca Borsatto-Galera, Roger William De Lábio, Spencer Luiz Marques Payão and Marília de Arruda Cardoso Smith * Disciplina de Genética – Departamento de Morfologia e Genética, UNIFESP/EPM, Rua Botucatu, 740 – Vila Clementino, CEP: 04023-900, São Paulo, SP, Brasil Abstract: Objective: We aimed to investigate whether rRNA 28S/18S levels decrease with aging in Down Syndrome (DS) individuals and whether these decreased levels are tissue-specific. Methods: We investigated mature rRNA 28S/18S levels by Northern Blotting in blood cells from 21 younger and 21 older DS individuals in comparison to 42 age-sex-matched controls. We also investigated these levels in oral mucosa and in blood cells from the same DS individuals. Results: All DS subjects showed no clinical signs of dementia at the time of the study. We did not detect differences in rRNA 28S/18S levels among DS and control groups concerning either aging process or cell types. Conclusions: Aging process in DS individuals was not characterized by reduced rDNA transcriptional activity and did not indicate a preclinical marker of AD in older DS subjects. Keywords: Down´s syndrome, Trisomy 21, Ageing, Ribosomal Genes Expression, rRNA. INTRODUCTION Loss of ribosomal genes has been observed in the aging process of many cell types, such as nervous tissue, cardiac and skeletal striated muscles as well as inhuman adipocytes. Alterations in rRNA biogenesis have also been associated with many diseases [1, 2]. A reduced ribosomal genes tran- scriptional activity and a preferential degradation of the ma- jor 28S subunit in relation to 18S have been verified in leu- kocytes from patients with Alzheimer disease (AD) [3-5]. Most of the clinical signs associated with normal aging occur prematurely in adult individuals with Down syndrome (DS) who also show early cognitive decline and generally develop neuropathological signs of AD [6]. A previous study conducted by our laboratory confirmed the progressive loss of chromosome 21 with age, in 2-4% of cells, in DS individuals, originally reported by Percy et al. [7], who called it an “occult mosaicism”. Therefore, older DS should be considered individuals with low levels of cel- lular mosaicism which could contribute to the phenotypic variance and to AD. We previously reported a significant decrease of satellite association and AgNOR staining frequencies in lymphocyte chromosomes carrying Nucleolar Organizer Regions (NOR) from older DS in relation to younger DS [8]. Literature shows controversial evidence regarding AgNOR staining frequencies in chromosomes from older DS individuals. *Address correspondence to this author at the Disciplina de Genética – Departamento de Morfologia e Genética, UNIFESP/EPM, Rua Botucatu, 740 – Vila Clementino, CEP: 04023-900, São Paulo, SP, Brasil; Tel: 55-11-5576 4260; Fax: 55-11-5576 4260; E-mail: macsmith.morf@epm.br Increase in the rDNA expression has been detected in lac- tents and infants with DS using this technique and Dermitas [9] proposed that this increase in ribosome biogenesis lead- ing to disturbed protein synthesis may contribute to DS phe- notype [9-13]. Reduction in the ability or protein synthesis, quantity of 5.8S and 5S rRNA, tRNA and an increase in the oxidation of RNAs were detected in the cerebral cortex of post-mortem patients exhibiting mild cognitive impairment and AD [14, 15]. The authors proposed that ribosome function alterations may be an important marker in AD pathogenesis. Addicion- ally, Honda et al. [16] suggested that rRNA acts as a redox center within the neuronal cells probably associated with reduction of protein synthesis. The aim of our study was to investigate rDNA transcrip- tional activity through mature rRNA 28S/18S levels in younger and older DS subjects in two distinct tissues show- ing different embryonic origins and cell types and in age- sex-matched-controls. Thus, we selected blood cells, meso- derm-derived cells and oral mucosa cells, neuroectoderm- derived cells which share the same embryonic origin as neu- ral cells. This is the first report comparing ribosomal tran- scriptional function in two different tissues from younger and older DS individuals. METHODS Procedure Patients were recruited at the Center of Dental Treatment for Mentally Disabled (CAOE). 42 DS individuals and 42 controls were separated into 4 groups: younger DS patients (YD); elder DS patients (ED); younger control subjects