The peculiar aging of human liver: A geroscience perspective within transplant context

Morsiani, Cristina; Bacalini, Maria Giulia; Santoro, Aurelia; Garagnani, Paolo; Collura, Salvatore; D’Errico, Antonietta; Eguileor, Magda de; Grazi, Gian Luca; Cescon, Matteo; Franceschi, Claudio; Capri, Miriam

doi:10.1016/j.arr.2019.02.002

Cited by 42 publications

(35 citation statements)

References 133 publications

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“…[196][197][198] On the other hand, there is a clinical evidence that orthotopic liver transplants from aged donors are comparable to those from young donors. 199 We propose significant progress on the roles of ncRNA in aging liver as many transplants in clinic are from people more than 70 to 80 years old.…”

Section: Resultsmentioning

confidence: 99%

Noncoding RNA in Liver Regeneration—From Molecular Mechanisms to Clinical Implications

2019

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The unique ability of the adult liver to regenerate after injury is the basis for efficient surgical resection and liver transplantation and provides solutions for the treatment of liver cancer and acute liver failure. Current success in surgical treatments could be enhanced by directed regulation of liver regeneration. A number of small molecules and growth factors have been tested in mice models to improve liver regeneration. Noncoding ribonucleic acids (ncRNA) are less studied regulators of various cellular processes. Here, the authors carefully review ncRNA involved in liver regeneration and discuss molecular mechanisms and regulatory networks. These ncRNAs modulate the expression of pro- and antiproliferative genes allowing to orchestrate precisely the proliferation of hepatocytes. The authors expect that ncRNA will become new targets in liver regeneration due to recent progress in therapeutic nucleic acids. Among a large number of preclinical studies on ncRNA, only a few entered clinical trials, and further studies are needed to uncover their potential as therapeutic targets.

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Section: Resultsmentioning

confidence: 99%

Noncoding RNA in Liver Regeneration—From Molecular Mechanisms to Clinical Implications

2019

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“…Several evidence supports a central role of ribosome regulation during aging: ribosomal proteins are overrepresentated in studies investigating age-associated transcriptomic changes [49], and the association between small nucleoli and longevity has been reported [50]. We focused our attention on liver, a key metabolic organ that undergoes a relatively successful aging when compared to other body districts [51] and that is characterized by specific epigenomic and transcriptomic age-associated changes [52].…”

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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“…On the other hand, the experimental protocol allows the assessment of interactions between other important variables studied. We also considered the effect of aging on our experimental protocol, since lipogenesis and fat accumulation leading to liver steatosis are both part of the natural aging process of the liver [ 35 , 36 ]. Accordingly, we used age-matched animals, as control groups, and the effect of time as a covariable was discarded due to a non-significant correlation between both variables.…”

Section: Discussionmentioning

confidence: 99%

Effects of high-intensity infrasound on liver lipid content of rats

Pereira

Santos

et al. 2020

Heliyon

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Previous experimental studies show that exposure to noise with high and audible frequencies causes multiple metabolic alterations, such as increased liver glycogen and triglycerides. However, the effect of exposure to sound with lower frequencies, such as high-intensity infrasound (frequency <20 Hz and sound pressure level >90 dB), on the liver lipid content is still unclear. As such, we aimed to study the effect of exposure to high-intensity infrasound of both normal and glucose intolerant rats on the liver lipid content. For this study, 79 wild-type male Wistar rats were randomly divided into two groups: G1, no treatment, and G2, induced glucose intolerance. Each of these two groups was randomly divided in two subgroups: s (animals kept in silence) and i (animals continuously exposed to high-intensity infrasound noise). At three noise-exposure time-points (1, 6 and 12 weeks) the rats were sacrificed, the liver was excised and hepatic lipids extracted. Data analysis was performed using a two-way ANOVA (p = 0.05). No significant effects due to interactions between the several factors exist on the liver lipid content (p=0.077). Moreover, no significant effects due to infrasound exposure (p=0.407) or glucose tolerance status (p=0.938) were observed. Our study shows that continuous exposure to high-intensity infrasound has no influence on the lipid content of the liver of both normal and glucose intolerant animals. This finding reinforces the need for further experimental studies on the physiological effects of infrasound due to its possible hazardous effects on human health.

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The peculiar aging of human liver: A geroscience perspective within transplant context

Cited by 42 publications

References 133 publications

Noncoding RNA in Liver Regeneration—From Molecular Mechanisms to Clinical Implications

Noncoding RNA in Liver Regeneration—From Molecular Mechanisms to Clinical Implications

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

Effects of high-intensity infrasound on liver lipid content of rats

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