rRNA-gene methylation and biological aging

D’Aquila, Patrizia; Bellizzi, Dina; Passarino, Giuseppe

doi:10.18632/aging.101369

Cited by 6 publications

(3 citation statements)

References 7 publications

(7 reference statements)

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“…At the same time, it should be noted that, in humans, rDNA hypermethylation has been associated to age-related conditions and pathologies, including Werner syndrome (WS) [53] and a decrease in cognitive performance and survival chance [37,54]. Tissue-specific hypermethylation was also described in brain samples from patients with mild cognitive impairment and Alzheimer's disease [55].…”

Section: Discussionmentioning

confidence: 99%

Aging and Caloric Restriction Modulate the DNA Methylation Profile of the Ribosomal RNA Locus in Human and Rat Liver

Gensous¹,

Ravaioli²,

Pirazzini

et al. 2020

Nutrients

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A growing amount of evidence suggests that the downregulation of protein synthesis is an adaptive response during physiological aging, which positively contributes to longevity and can be modulated by nutritional interventions like caloric restriction (CR). The expression of ribosomal RNA (rRNA) is one of the main determinants of translational rate, and epigenetic modifications finely contribute to its regulation. Previous reports suggest that hypermethylation of ribosomal DNA (rDNA) locus occurs with aging, although with some species- and tissue- specificity. In the present study, we experimentally measured DNA methylation of three regions (the promoter, the 5′ of the 18S and the 5′ of 28S sequences) in the rDNA locus in liver tissues from rats at two, four, 10, and 18 months. We confirm previous findings, showing age-related hypermethylation, and describe, for the first time, that this gain in methylation also occurs in human hepatocytes. Furthermore, we show that age-related hypermethylation is enhanced in livers of rat upon CR at two and 10 months, and that at two months a trend towards the reduction of rRNA expression occurs. Collectively, our results suggest that CR modulates age-related regulation of methylation at the rDNA locus, thus providing an epigenetic readout of the pro-longevity effects of CR.

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“…The m6As of certain mRNA in blood cells were found to be lower with age than in young human blood cells [ 9 ]. The methylation promoter region of mouse rRNA gradually and uniformly increases with age [ 10 ]. We hypothesized that RNA methylation was a link between aging and cancer.…”

Section: Dear Editormentioning

confidence: 99%

A pan-cancer analysis of the oncogenic role of leucine zipper protein 2 in human cancer

et al. 2022

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In this study, we aimed to perform a pan-cancer analysis of leucine zipper protein 2 (LUZP2). A standardized TCGA pan-cancer dataset was downloaded. Differential expression, clinical prognosis, genetic mutations, immune infiltration, epigenetic modifications, tumor stemness and heterogeneity were analyzed. We conducted all analyses through software R 3.6.3 and its suitable packages. Compared to normal samples, we observed that the LUZP2 mRNA expression was significantly upregulated in LGG, PRAD, LUSC and downregulated in KIRC and other eleven cancer species patients. In terms of overall survival, low-expression of LUZP2 was significantly associated with poor prognosis in lower grade glioma (LGG), lung squamous cell carcinoma (LUSC), kidney renal clear cell carcinoma (KIRC) and prostate adenocarcinoma (PRAD). For progression-free survival, we observed that downregulation of LUZP2 was significantly related to LGG, KIRC, LUSC, and PRAD. Our results observed negative correlations of the stemness of LGG and PRAD with the mRNA expression of LUZP2, whose downregulation was closely associated with poor prognosis. The mutation frequencies of LGG, PRAD, KIRC, and LUSC were 0.4%, 0.4%, 0.3%, and 2.1%, respectively. We detected that the LUZP2 level was negatively associated with TILs in most cancers, including LGG, LUSC, PRAD, and KIRC, while the LUZP2 methylation showed the opposite results. In conclusion, the results of our initial pan-cancer investigation provided a somewhat thorough understanding of the functions of LUZP2 on KIRC, LGG, PRAD, and LUSC.

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“…In this context, in addition to non-directional changes in DNA methylation patterns, referred to as epigenetic drift, directional, and non-stochastic hyper- or hypo-methylation events, occurring over time at discrete CpG sites throughout the genome, turned out to be very useful, and also able to be predictive of both chronological and biological aging (3–7). These age-Differentially Methylated Regions (a-DMRs) have been found associated with survival chance, disability, frailty, multi-morbidity, thus determining the overall variation in life expectancy (8–12). What is more, the setup of a series of multi-tissue age estimator models, namely epigenetic clocks, is allowing the prediction of all-cause mortality independent of several risk factors (13–24).…”

Section: Introductionmentioning

confidence: 99%

Mini Nutritional Assessment Scores Indicate Higher Risk for Prospective Mortality and Contrasting Correlation With Age-Related Epigenetic Biomarkers

et al. 2019

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The plasticity of the individual epigenetic landscape that goes to countless rearrangements throughout life is closely the reflection of environmental factors such as chemical exposure, socio-economic status and nutrient intakes both early and late in life. The Mini Nutritional Assessment (MNA) is a well-validated tool for assessing malnutrition in old people. It includes 6 (MNA-SF) or 18 (MNA-LF) self-reported questions derived from general, anthropometric, dietary, and self- assessment. We evaluated the association between the nutritional status, as measured by MNA, and methylation biomarkers we previously demonstrated to be associated with chronological and biological age in human. We found that malnutrition is positively correlated with DNA methylation status at the global level, in line with our previous reports. On the contrary, most of the sites located within specific genes, which were previously reported to be correlated with chronological and biological aging, showed to be not affected by malnutrition, or even to have correlations with malnutrition opposite to those previously reported with frailty. These results may suggest that malnutrition is among the first effects of disability and other age- related problems and a generalized non-specific epigenetic remodeling may be the initial response of the organism. By contrast, the fine remodeling of specific genomic sites is scarcely affected by malnutrition and may respond to a more complex interaction of different factors. Therefore, although malnutrition in the elderly is certainly a risk factor for survival, this is partially independent of the aging process of the organism which leads to the methylation remodeling previously described to measure chronological and biological aging.

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rRNA-gene methylation and biological aging

Cited by 6 publications

References 7 publications

Aging and Caloric Restriction Modulate the DNA Methylation Profile of the Ribosomal RNA Locus in Human and Rat Liver

A pan-cancer analysis of the oncogenic role of leucine zipper protein 2 in human cancer

Mini Nutritional Assessment Scores Indicate Higher Risk for Prospective Mortality and Contrasting Correlation With Age-Related Epigenetic Biomarkers

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