Chronic stress is associated with a higher risk for carcinogenesis as well as age-related diseases and immune dysfunction. There is evidence showing that psychological stress can contribute to premature immunosenescence. Therefore, the question arose whether chronic exposure to catecholamine could drive immune cells into senescence.
View Article and Find Full Text PDFIn recent times, exploring the protective potential of medicinal plants has attracted increasing attention. To fight reactive oxygen species (ROS), which are key players in hepatic, cerebral and renal diseases, scientists have directed their efforts towards identifying novel compounds with antioxidant effects. Due to its unique composition, significant attention has been given to Cactus Seed Oil (CSO).
View Article and Find Full Text PDFTelomerase is a reverse transcriptase that consists of the telomerase reverse transcriptase (TERT) protein and the telomerase RNA component TERC which also harbors the template region for telomere synthesis. In its canonical function the enzyme adds single-stranded telomeric hexanucleotides de novo to the ends of linear chromosomes, telomeres, in telomerase-positive cells such as germline, stem- and cancer cells. This potential biochemical activity of telomerase can be measured with the help of a telomerase repeat amplification protocol (TRAP) which often includes a PCR amplification due to the low abundance of telomerase in most cells and tissues.
View Article and Find Full Text PDFSeventeen papers published in 2019 and early 2020 demonstrate the ongoing interest and research concerning telomeres and telomerase in aging and cancer [...
View Article and Find Full Text PDFTelomerase, consisting of the protein subunit telomerase reverse transcriptase (TERT) and RNA component TERC, is best known for maintaining and extending human telomeres, the ends of linear chromosomes, in tissues, where it is active, such as stem cells, germline cells, lymphocytes and endothelial cells. This function is considered as canonical. However, various non-canonical functions for the protein part TERT have been discovered.
View Article and Find Full Text PDFMost people associate the enzyme telomerase with its role in maintaining telomeres, which is its best-known canonical role. For this important function, two main components are required: the protein telomerase reverse transcriptase (TERT) and the telomerase RNA component. In addition, over the last decades, an ever-growing number of other, non-telomeric, non-canonical functions for the telomerase protein TERT has been established.
View Article and Find Full Text PDFHypertrophy in white adipose tissue (WAT) can result in sustained systemic inflammation, hyperlipidaemia, insulin resistance, and onset of senescence in adipocytes. Inflammation and hypertrophy can be induced in vitro using palmitic acid (PA). WAT adipocytes have innately low β-oxidation capacity, while inorganic nitrate can promote a beiging phenotype, with promotion of β-oxidation when cells are exposed to nitrate during differentiation.
View Article and Find Full Text PDFDue to their close connection with senescence, aging, and disease, telomeres and telomerase provide a unique and vital research route for boosting longevity and health span. Despite significant advances during the last three decades, earlier studies into these two biological players were impeded by the difficulty of achieving real-time changes inside living cells. As a result of the clustered regularly interspaced short palindromic repeats (CRISPR)-associated system's (Cas) method, targeted genetic studies are now underway to change telomerase, the genes that govern it as well as telomeres.
View Article and Find Full Text PDFMechanotransduction is defined as the ability of cells to sense mechanical stimuli from their surroundings and translate them into biochemical signals. Epidermal keratinocytes respond to mechanical cues by altering their proliferation, migration, and differentiation. In vitro cell culture, however, utilises tissue culture plastic, which is significantly stiffer than the in vivo environment.
View Article and Find Full Text PDFTelomerase is an enzyme that in its canonical function extends and maintains telomeres, the ends of chromosomes. This reverse transcriptase function is mainly important for dividing cells that shorten their telomeres continuously. However, there are a number of telomere-independent functions known for the telomerase protein TERT (Telomerase Reverse Transcriptase).
View Article and Find Full Text PDFThe mammalian sirtuin family consists of seven proteins, three of which (SIRT3, SIRT4, and SIRT5) localise specifically within mitochondria and preserve mitochondrial function and homeostasis. Mitochondrial sirtuins are involved in diverse functions such as deacetylation, ADP-ribosylation, demalonylation and desuccinylation, thus affecting various aspects of cell fate. Intriguingly, mitochondrial sirtuins are able to manage these delicate processes with accuracy mediated by crosstalk between the nucleus and mitochondria.
View Article and Find Full Text PDFIron-overload is a well-known cause for the development of chronic liver diseases and known to induce DNA damage. The protective effect of argan oil (AO) from the fruit and olive oil (OO) (6% AO or OO for 28 days) was evaluated on a mouse model of iron overload (3.5mg Fe/liter) and in human fibroblasts where DNA damage was induced via culture under hyperoxia (40% oxygen).
View Article and Find Full Text PDFCellular senescence is characterized by an irreversible cell cycle arrest as well as a pro-inflammatory phenotype, thought to contribute to aging and age-related diseases. Neutrophils have essential roles in inflammatory responses; however, in certain contexts their abundance is associated with a number of age-related diseases, including liver disease. The relationship between neutrophils and cellular senescence is not well understood.
View Article and Find Full Text PDFAgeing is a multifactorial process associated with reduced function and increased risk of morbidity and mortality. Recently, nine cellular and molecular hallmarks of ageing have been identified, which characterise the ageing process, and collectively, may be key determinants of the ageing trajectory. These include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication.
View Article and Find Full Text PDFDyskerin is a core-component of the telomerase holo-enzyme, which elongates telomeres. Telomerase is involved in endometrial epithelial cell proliferation. Most endometrial cancers (ECs) have high telomerase activity; however, dyskerin expression in human healthy endometrium or in endometrial pathologies has not been investigated yet.
View Article and Find Full Text PDFTelomeres protect chromosomal ends and they are maintained by the specialised enzyme, telomerase. Endometriosis is a common gynaecological disease and high telomerase activity and higher hTERT levels associated with longer endometrial telomere lengths are characteristics of eutopic secretory endometrial aberrations of women with endometriosis. Our ex-vivo study examined the levels of hTERC and DKC1 RNA and dyskerin protein levels in the endometrium from healthy women and those with endometriosis ( = 117).
View Article and Find Full Text PDFTelomeres are transcribed as long non-coding RNAs called TERRAs (Telomeric repeat containing RNA) that participate in a variety of cellular regulatory functions. High telomerase activity (TA) is associated with endometrial cancer (EC). This study aimed to examine the levels of three TERRAs, transcribed at chromosomes 1q-2q-4q-10q-13q-22q, 16p and 20q in healthy ( = 23) and pathological ( = 24) human endometrium and to examine their association with cellular proliferation, TA and telomere lengths.
View Article and Find Full Text PDFProtective effects of the telomerase protein TERT have been shown in neurons and brain. We previously demonstrated that TERT protein can accumulate in mitochondria of Alzheimer's disease (AD) brains and protect from pathological tau in primary mouse neurons. This prompted us to employ telomerase activators in order to boost telomerase expression in a mouse model of Parkinson's disease (PD) overexpressing human wild type α-synuclein.
View Article and Find Full Text PDFBackground: Non-ST elevation acute coronary syndrome (NSTEACS) occurs more frequently in older patients with an increased occurrence of recurrent cardiac events following the index presentation. Telomeres are structures consisting of repeated DNA sequences as associated shelterin proteins at the ends of chromosomes. We aim to determine whether telomere length (TL) and telomerase activity (TA) predicted poor outcomes in older patients presenting with NSTEACS undergoing invasive care.
View Article and Find Full Text PDFBackground: Cognitive decline is a frequent complication of Parkinson's disease (PD) and the identification of predictive biomarkers for it would help in its management.
Objective: Our aim was to analyse whether senescence markers (telomere length, p16 and p21) or their change over time could help to better predict cognitive and motor progression of newly diagnosed PD patients. We also compared these senescence markers to previously analysed markers of inflammation for the same purpose.
Telomerase is best known for its function in maintaining telomeres but has also multiple additional, non-canonical functions. One of these functions is the decrease of oxidative stress and DNA damage due to localisation of the telomerase protein TERT into mitochondria under oxidative stress. However, the exact molecular mechanisms behind these protective effects are still not well understood.
View Article and Find Full Text PDFTelomeres at the termini of human chromosomes are shortened with each round of cell division due to the "end replication problem" as well as oxidative stress. During carcinogenesis, cells acquire or retain mechanisms to maintain telomeres to avoid initiation of cellular senescence or apoptosis and halting cell division by critically short telomeres. The unique reverse transcriptase enzyme complex, telomerase, catalyzes the maintenance of telomeres but most human somatic cells do not have sufficient telomerase activity to prevent telomere shortening.
View Article and Find Full Text PDFTelomeres are specialised structures at the end of linear chromosomes. They consist of tandem repeats of the hexanucleotide sequence TTAGGG, as well as a protein complex called shelterin. Together, they form a protective loop structure against chromosome fusion and degradation.
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