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The SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokine release, and immunosuppression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called persistent post-COVID-19 syndrome (PPCS) is a common finding. In COVID-19 survivors, PPCS presents one or more symptoms: fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. In this study, a cohort of 117 COVID-19 survivors (post-COVID-19) and 144 non-infected volunteers (COVID-19-free) was analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. The results show a consistent biological age increase in the post-COVID-19 population, determining a DeltaAge acceleration of 10.45 ± 7.29 years (+5.25 years above the range of normality) compared with 3.68 ± 8.17 years for the COVID-19-free population ( p < 0.0001). A significant telomere shortening parallels this finding in the post-COVID-19 cohort compared with COVID-19-free subjects ( p < 0.0001). Additionally, ACE2 expression was decreased in post-COVID-19 patients, compared with the COVID-19-free population, while DPP-4 did not change. In light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID-19 condition, particularly in younger patients (< 60 years).

The short-lived turquoise killifish Nothobranchius furzeri (Nfu) is a valid model for aging studies. Here, we investigated its age-associated cardiac function. We observed oxidative stress accumulation and an engagement of microRNAs (miRNAs) in the aging heart. MiRNA-sequencing of 5 week (young), 12-21 week (adult) and 28-40 week (old) Nfu hearts revealed 23 up-regulated and 18 down-regulated miRNAs with age. MiR-29 family turned out as one of the most up-regulated miRNAs during aging. MiR-29 family increase induces a decrease of known targets like collagens and DNA methyl transferases (DNMTs) paralleled by 5´methyl-cytosine (5mC) level decrease. To further investigate miR-29 family role in the fish heart we generated a transgenic zebrafish model where miR-29 was knocked-down. In this model we found significant morphological and functional cardiac alterations and an impairment of oxygen dependent pathways by transcriptome analysis leading to hypoxic marker up-regulation. To get insights the possible hypoxic regulation of miR-29 family, we exposed human cardiac fibroblasts to 1% O 2 levels. In hypoxic condition we found miR-29 down-modulation responsible for the accumulation of collagens and 5mC. Overall, our data suggest that miR-29 family up-regulation might represent an endogenous mechanism aimed at ameliorating the age-dependent cardiac damage leading to hypertrophy and fibrosis.

Age is the most important risk factor for metabolic alterations and cardiovascular accidents. Although class III histone deacetylases, alias Sirtuins, have been appealed as "the fountain of youth" their role in longevity control and prevention of aging-associated disease is still under debate. Indeed, several lines of evidence indicate that sirtuin activity is strictly linked to metabolism and dependent on NAD(+) synthesis both often altered as aging progresses. During aging the cardiovascular system is attacked by a variety of environmental stresses, including those determined by high blood glucose and lipid levels, or by the presence of oxidized lipoproteins which, among others, determine important oxidative stress signals. In such a milieu, heart and vessels develop a functional impairment leading to atherosclerosis, ischemia, heart insufficiency and failure. Sirtuins, which are believed to have a positive impact on cardiovascular physiology and physiopathology, are distributed in different subcellular compartments including the nucleus, the cytoplasm and the mitochondria, where they regulate expression and function of a large variety of target genes and proteins. Remarkably, experimental animal models indicate resveratrol, the first natural compound described to positively regulate the activity of sirtuins, as able to protect the endothelium and the heart exposed to a variety of stress agents. This review will focus on the regulation and function of mammalian sirtuins with special attention paid to their role as cardiovascular "defenders" giving indication of their targets of potential relevance for the development of future therapeutics. This article is part of a Special Issue entitled CV Aging., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

RNA epigenetics is perhaps the most recent field of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combinations whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining changes in RNA structure are in common with those involved in DNA and chromatin structure regulation, while other molecules seem very specific to RNA. It is envisaged, then, that new small molecules, acting selectively on RNA epigenetic changes, will be reported soon, opening new therapeutic interventions based on the correction of the RNA epigenetic landscape. In this review, we shall summarize some aspects of RNA epigenetics limited to those in which the potential clinical translatability to cardiovascular disease is emerging [ABSTRACT FROM AUTHOR]

Hormones and nitric oxide (NO), a free radical, are ancestral molecules, conserved through evolution, that modulate many aspects of the physiology and pathophysiology of living organisms by regulating transcription of genes involved in development, metabolism, and differentiation. Of interest, both estrogen and NO signaling, specifically through the estrogen receptor-α (ERα) and the endothelial isoform of the nitric oxide synthase (eNOS), have been shown to counteract endothelial senescence through a shared downstream effector, the catalytic subunit of human telomerase (hTERT), a key molecule in the aging process. Since aging is the first and most relevant risk factor in cardiovascular diseases, it is tempting to speculate that hTERT may be at the cross point between the NO and estrogen pathways. The present review will focus on the evolutionary and molecular aspects linking eNOS, ERs, and hTERT in counteracting the process of endothelial cell aging. [ABSTRACT FROM AUTHOR]

The WHO estimated around 41 million deaths worldwide each year for age-related non-communicable chronic diseases. Hence, developing strategies to control the accumulation of cell senescence in living organisms and the overall aging process is an urgently needed problem of social relevance. During aging, many biological processes are altered, which globally induce the dysfunction of the whole organism. Cell senescence is one of the causes of this modification. Nowadays, several drugs approved for anticancer therapy have been repurposed to treat senescence, and others are under scrutiny in vitro and in vivo to establish their senomorphic or senolytic properties. In some cases, this research led to a significant increase in cell survival or to a prolonged lifespan in animal models, at least. Senomorphics can act to interfere with a specific pathway in order to restore the appropriate cellular function, preserve viability, and to prolong the lifespan. On the other hand, senolytics induce apoptosis in senescent cells allowing the remaining non–senescent population to preserve or restore tissue function. A large number of research articles and reviews recently addressed this topic. Herein, we would like to focus attention on those chemical agents with senomorphic or senolytic properties that perspectively, according to literature, suggest a potential application as senotherapeutics for chronic diseases. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a sex-steroid hormone-dependent cancer in which estrogens play a critical role in both initiation and progression. Recently, several long non-coding RNAs (lncRNAs) have been associated with PCa and are supposedly playing a pivotal role in the biology and progression of this type of cancer. In this review, we focused on some lncRNAs that are known for their androgen and estrogen transcriptional responsiveness in PCa. Specifically, we summarized recent pieces of evidence about lncRNAs NEAT1, H19, MALAT1, and HOTAIR, in estrogen signaling, emphasizing their role in PCa progression and the acquisition of a castration-resistant phenotype. Here, the reader will find information about lncRNAs present in estrogen-dependent transcriptional complexes. The potential role of lncRNA/estrogen signaling as a novel pathway for PCa treatment will be discussed. [ABSTRACT FROM AUTHOR]