Evaluation of telomere length and telomerase activity on predicting in vitro fertilization treatment outcomes.

The current article is a literature review aiming to provide an overview of the existing knowledge on the association between telomere length and telomerase activity and in vitro fertilization. Recently, telomeres have been used as an effective biomarker to determine biological age, which may differ from chronological age due to genetic, lifestyle, and environmental factors. Cellular senescence, along with other exogenous and mainly environmental factors, can enhance telomere wear, further shortening their ends and may also affect reproductive aging. IVF is a common fertility treatment caused by female reasons (age, ovulation disorders, damaged or blocked fallopian tubes, endometriosis), male reasons (low sperm quantity or quality), or unexplained infertility. A growing number of studies have proposed a relationship between telomere length and telomerase activity and IVF success and have suggested their use as candidate biomarkers for IVF outcome. Nevertheless, additional studies are necessary to be conducted, in order to clarify the possible implication of telomeres in IVF and to evaluate their possible role as valuable predictors of IVF result.

Assessing locomotory rate in response to food for the identification of neuronal and muscular defects in C. elegans.

C. elegans is a bacteria-eating soil-dwelling nematode. Typical cultivation of laboratory-reared populations occurs on bacteria-covered solid media, where they move along with sinusoidal undulations. Nematodes decelerate when they encounter food. Dopaminergic and serotonergic neurotransmission regulate this behavior. Here, we describe the procedure for determining food-dependent locomotion rate of fed and fasting nematodes. We detail steps for assay plate preparation, C. elegans synchronization, and assessment of locomotion. The behaviors we describe provide information regarding the animal's physiological neuronal and muscular function. For complete details on the use and execution of this protocol, please refer to Petratou et al. (2023)1 and Sawin et al. (2000).2.

Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy.

Cancer of the colon and rectum (CRC) has been identified among the three most prevalent types of cancer and cancer-related deaths for both sexes. Even though significant progress in surgical and chemotherapeutic techniques has markedly improved disease-free and overall survival rates in contrast to those three decades ago, recent years have seen a stagnation in these improvements. This underscores the need for new therapies aiming to augment patient outcomes. A number of emerging strategies, such as immune checkpoint inhibitors (ICIs) and adoptive cell therapy (ACT), have exhibited promising outcomes not only in preclinical but also in clinical settings. Additionally, a thorough appreciation of the underlying biology has expanded the scope of research into potential therapeutic interventions. For instance, the pivotal role of altered telomere length in early CRC carcinogenesis, leading to chromosomal instability and telomere dysfunction, presents a promising avenue for future treatments. Thus, this review explores the advancements in CRC immunotherapy and telomere-targeted therapies, examining potential synergies and how these novel treatment modalities intersect to potentially enhance each other's efficacy, paving the way for promising future therapeutic advancements.

Benefits of Quercetin on Glycated Hemoglobin, Blood Pressure, PiKo-6 Readings, Night-Time Sleep, Anxiety, and Quality of Life in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial.

Background: Diabetes is a rapidly growing global morbidity issue with high prevalence, and the associated dysglycemia leads to complications. Patients with type 2 diabetes mellitus (T2DM) often experience elevated anxiety levels, affecting their quality of life and diabetes management. This study investigated quercetin, a nutraceutical and potential senolytic with antioxidant activity, to detect its possible positive effect on the bio-clinical measurements and routine health of patients with T2DM. Methods: This prospective randomized controlled trial (RCT) investigated the clinical usefulness of quercetin in patients with T2DM receiving non-insulin medications. One hundred participants were stratified by age and sex (1:1) and randomized to control (n = 50) or intervention (n = 50) groups. The control received standard care only, while the intervention received 500 mg quercetin daily for 12 weeks, followed by an 8-week washout and a final consecutive 12-week supplementation period (total: 32 weeks), as adjunct to their usual care. Comprehensive health assessments, including blood analyses, were conducted at baseline and study termination. Quality of life and anxiety were assessed using the 36-item Short Form Health Survey (SF-36) and Short Anxiety Screening Test (SAST-10). Results: Eighty-eight patients with T2DM concluded the trial. Compared with the control, glycated hemoglobin (HbA1c) levels showed a significant decrease (Δ%-change: -4.0% vs. 0.1%, p = 0.011). Quercetin also significantly improved PiKo-6 readings (FEV1: 5.6% vs. -1.5%, p = 0.002), systolic blood pressure (-5.0% vs. -0.2%, p = 0.029), night-time sleep (11.6% vs. -7.3%, p < 0.001), anxiety levels (SAST-10) (-26.2% vs. 3.3%, p < 0.001), and quality of life (SF-36) (both physical and mental components, p < 0.001). Conclusions: Based on the current open-label study, quercetin appears to be a promising supplement for T2DM, providing lifestyle and care support. Further research is warranted to shift this potential from clinical usefulness and feasibility to multidisciplinary evidence.

Predictive value of the sFlt­1/PlGF ratio in women with suspected preeclampsia: An update (Review).

Preeclampsia (PE) is a major complication of pregnancy with an incidence rate of 2­8% and is a leading cause of maternal mortality and morbidity. The various consequences of severe preeclampsia for the fetus, neonate and child include intrauterine growth retardation (IUGR), fetal hypoxia, oligohydramnios, intrauterine fetal demise, increased perinatal mortality and morbidity, neurodevelopmental disorders and even irreversible brain damage (cerebral palsy). A number of studies have demonstrated that differences in maternal serum concentrations of angiogenic factors between preeclampsia and normotensive pregnancies can be used as biomarkers, either alone or in combination with other markers, to predict the development of PE. The presence in the maternal circulation of two proteins of placental origin, placental growth factor (PlGF) and soluble fms­like tyrosine kinase 1 (sFlt­1), has been shown to be of clinical value, as the sFlt­1/PlGF ratio appears to be the optimal predictive tool for the development of PE. The measurement of their concentration in maternal serum in screening models, serves as predictive marker for the development of PE or IUGR later in gestation. However, further research is required to improve its clinical applicability and provide guidelines for its use worldwide to achieve more consistent clinical management of women with PE.

Telomere length as a predictive biomarker in osteoporosis (Review).

Telomeres are the ends of chromosomes that protect them from DNA damage. There is evidence to suggest that telomere shortening appears with advanced age. Since aging is a significant risk factor for developing age-related complications, it is plausible that telomere shortening may be involved in the development of osteoporosis. The present review summarizes the potential of telomere shortening as a biomarker for detecting the onset of osteoporosis. For the purposes of the present review, the following scientific databases were searched for relevant articles: PubMed/NCBI, Cochrane Library of Systematic Reviews, Scopus, Embase and Google Scholar. The present review includes randomized and non-randomized controlled studies and case series involving humans, irrespective of the time of their publication. In six out of the 11 included studies providing data on humans, there was at least a weak association between telomere length and osteoporosis, with the remaining studies exhibiting no such association. As a result, telomere shortening may be used as a biomarker or as part of a panel of biomarkers for tracking the onset and progression of osteoporosis.

A novel nutraceutical formulation increases telomere length and activates telomerase activity in middle­aged rats.

Telomeres are major contributors to cell fate and aging through their involvement in cell cycle arrest and senescence. The accelerated attrition of telomeres is associated with aging­related diseases, and agents able to maintain telomere length (TL) through telomerase activation may serve as potential treatment strategies. The aim of the present study was to assess the potency of a novel telomerase activator on TL and telomerase activity in vivo. The administration of a nutraceutical formulation containing Centella asiatica extract, vitamin C, zinc and vitamin D3 in 18­month­old rats for a period of 3 months reduced the telomere shortening rate at the lower supplement dose and increased mean the TL at the higher dose, compared to pre­treatment levels. TL was determined using the Q­FISH method in peripheral blood mononuclear cells collected from the tail vein of the rats and cultured with RPMI­1640 medium. In both cases, TLs were significantly longer compared to the untreated controls (P≤0.001). In addition, telomerase activity was increased in the peripheral blood mononuclear cells of both treatment groups. On the whole, the present study demonstrates that the nutraceutical formulation can maintain or even increase TL and telomerase activity in middle­aged rats, indicating a potential role of this formula in the prevention and treatment of aging­related diseases.

Role of telomere length in human carcinogenesis (Review).

Cancer is considered the most important clinical, social and economic issue regarding cause­specific disability­adjusted life years among all human pathologies. Exogenous, endogenous and individual factors, including genetic predisposition, participate in cancer triggering. Telomeres are specific DNA structures positioned at the end of chromosomes and consist of repetitive nucleotide sequences, which, together with shelterin proteins, facilitate the maintenance of chromosome stability, while protecting them from genomic erosion. Even though the connection between telomere status and carcinogenesis has been identified, the absence of a universal or even a cancer­specific trend renders consent even more complex. It is indicative that both short and long telomere lengths have been associated with a high risk of cancer incidence. When evaluating risk associations between cancer and telomere length, a disparity appears to emerge. Even though shorter telomeres have been adopted as a marker of poorer health status and an older biological age, longer telomeres due to increased cell growth potential are associated with the acquirement of cancer­initiating somatic mutations. Therefore, the present review aimed to comprehensively present the multifaceted pattern of telomere length and cancer incidence association.

Advancing athletic assessment by integrating conventional methods with cutting-edge biomedical technologies for comprehensive performance, wellness, and longevity insights.

In modern athlete assessment, the integration of conventional biochemical and ergophysiologic monitoring with innovative methods like telomere analysis, genotyping/phenotypic profiling, and metabolomics has the potential to offer a comprehensive understanding of athletes' performance and potential longevity. Telomeres provide insights into cellular functioning, aging, and adaptation and elucidate the effects of training on cellular health. Genotype/phenotype analysis explores genetic variations associated with athletic performance, injury predisposition, and recovery needs, enabling personalization of training plans and interventions. Metabolomics especially focusing on low-molecular weight metabolites, reveal metabolic pathways and responses to exercise. Biochemical tests assess key biomarkers related to energy metabolism, inflammation, and recovery. Essential elements depict the micronutrient status of the individual, which is critical for optimal performance. Echocardiography provides detailed monitoring of cardiac structure and function, while burnout testing evaluates psychological stress, fatigue, and readiness for optimal performance. By integrating this scientific testing battery, a multidimensional understanding of athlete health status can be achieved, leading to personalized interventions in training, nutrition, supplementation, injury prevention, and mental wellness support. This scientifically rigorous approach hereby presented holds significant potential for improving athletic performance and longevity through evidence-based, individualized interventions, contributing to advances in the field of sports performance optimization.

Τelomerase inhibitors and activators in aging and cancer: A systematic review.

The main aim of the present systematic review was to summarize the most frequently used telomerase regulators with an impact on aging and cancer that are referred to in in vitro and in vivo studies. For this purpose, a systematic review of the available literature on telomerase regulators referred to in articles from PubMed and Scopus libraries published from 2002 to 2021 and in accordance with PRISMA 2020 criteria, was conducted. Articles were included if they met the following criteria: They referred to telomerase modulators in aging and in cancer and were in vitro and/or in vivo studies, while studies that did not provide sufficient data or studies not written in English were excluded. In the present systematic review, 54 publications were included, of which 29 were full­text published studies, 11 were full­text reviews, 10 structure­based design studies and 4 abstracts are reported in this review. Telomerase regulators were then categorized as synthetic direct telomerase inhibitors, synthetic indirect telomerase inhibitors, synthetic telomerase activators, natural direct telomerase activators, natural telomerase inhibitors and natural indirect telomerase activators, according to their origin and their activity. On the whole, as demonstrated herein, telomerase regulators appear to be promising treatment agents in various age­related diseases. However, further in vivo and in vitro studies need to be performed in order to clarify the potentiality of telomerase as a therapeutic target.

Telomerase and telomeres in aging theory and chronographic aging theory (Review).

The current review focuses on the connection of telomerase and telomeres with aging. In this review, we describe the changes in telomerase and telomere length (TEL) during development, their role in carcinogenesis processes, and the consequences of reduced telomerase activity. More specifically, the connection of TEL in peripheral blood cells with the development of aging­associated diseases is discussed. The review provides systematic data on the role of telomerase in mitochondria, the biology of telomeres in stem cells, as well as the consequences of the forced expression of telomerase (telomerization) in human cells. Additionally, it presents the effects of chronic stress exposure on telomerase activity, the effect of TEL on fertility, and the effect of nutraceutical supplements on TEL. Finally, a comparative review of the chronographic theory of aging, presented by Olovnikov is provided based on currently available scientific research on telomere, telomerase activity, and the nature of aging by multicellular organisms.

Telomere length and telomerase activity in osteoporosis and osteoarthritis.

Osteoarthritis (OA) and osteoporosis (OP) are associated skeletal pathologies and have as a distinct feature the abnormal reconstruction of the subchondral bone. OA and OP have been characterized as age-related diseases and have been associated with telomere shortening and altered telomerase activity (TA). This review discusses the role of telomeres and telomerase in OA and OP pathologies and focuses on the usability of telomere length (TL) and the rate of telomere shortening as potential disease biomarkers. A number of studies have demonstrated that telomere shortening may contribute to OA and OP as an epigenetic factor. Therefore, it has been claimed that the measurement of TL of chondrocytes and/or peripheral blood cells may be an appropriate marker for the evaluation of the progression of these diseases. However, there is a need to be perform further studies with larger cohorts, with the aim of obtaining objective results and a better understanding of the association between TL, inflammation and aging, in order to provide further insight into the pathophysiology of degenerative joint diseases.

A novel approach regarding the anti-aging of facial skin through collagen reorganization.

The needle shaping technique can be used to perform subcutaneous microtransplants, enabling the 'lifting' of the skin. This prospective cohort study aimed to examine the effects of needle shaping on facial skin tone, volume and histological structure. A total of 54 women underwent the needle shaping procedure performed by inserting a tiny acupuncture needle combined with mixed electrical currents. The overall treatment was completed within 4 sessions of 2 months apart, once every 15 days. Maintenance was ensured by 2 sessions (no longer than 15 days apart) every 6 months. Macroscopic skin appearance was evaluated by a specialized dermatologist and the satisfaction of the patients was assessed. The microscopic structure of the skin dermis was evaluated by optic and scanning electron microscopy. I-chrome staining demonstrated more compact dermis-collagen fibers which were larger and thicker as compared to the controls. Scanning electron microscopy demonstrated an increased dermis thickness as compared to pre-treatment. All patients that answered to the follow up reported satisfaction during assessment. The satisfaction of the patients was very good and excellent in 45% of cases. The results of the needle-shaping procedure are natural with no scaring or down time. Moreover, the result is lasting even for 1 year, depending always on the subject's lifestyle and general health condition.

Developing BIOTEL: A Semi-Automated Spreadsheet for Estimating Telomere Length and Biological Age.

Introduction: Telomere length (TL) is causally related to aging and several age-related diseases. Specifically, the abundance of short telomeres and the rate of telomere shortening are strong determinants of cell homeostasis. Thus, tools for analyzing and manipulating TL data can vastly improve research focused on aging. Aim: In this study, we developed a semi-automated worksheet, BIOTEL, to generate individual and group TL statistics and provide a crude estimation of biological age. Results: Data from the Telomere Length Database Project (TLDP) were implemented to the spreadsheet to produce TL statistics. 150 participants were included, and their age was from 21 to 82 years, and the sex distribution ratio was 52.3%: 47.7% (male: female). Initially, we analyzed the fluorescence intensities of telomeres that were measured on metaphase spread leukocytes using three-dimensional (3D) quantitative-fluorescent in situ hybridization (Q-FISH) procedures (3D DNA FISH) with a (C3TA2)3 peptide nucleic acid (PNA) probe. Raw data of fluorescence intensities, demographic data and medical records from the participants were imported into the worksheet. Basic statistical analyses of TL data were provided through BIOTEL, including TL percentiles, specialized charts for TL distribution including the percentage of critically short telomeres (< 3,000 kilobases), individual telomere profiles, and graphs of biological age vs. chronological age. Conclusion: BIOTEL ver. 2.4 is a functional semi-automated worksheet that calculates a wide range of TL statistics, thus a useful tool with applications in research of telomeres and biological age estimation.

Discovery of potent telomerase activators: Unfolding new therapeutic and anti-aging perspectives.

Telomere length, a marker of cellular aging, decreases with age and it has been associated with aging­related diseases. Environmental factors, including diet and lifestyle factors, affect the rate of telomere shortening which can be reversed by telomerase. Telomerase activation by natural molecules has been suggested to be an anti­aging modulator that can play a role in the treatment of aging­related diseases. This study aimed to investigate the effect of natural compounds on telomerase activity in human peripheral blood mononuclear cells (PBMCs). The tested compounds included Centella asiatica extract formulation (08AGTLF), Astragalus extract formulation (Nutrient 4), TA­65 (containing Astragalus membranaceus extract), oleanolic acid (OA), maslinic acid (MA), and 3 multi­nutrient formulas (Nutrients 1, 2 and 3) at various concentrations. The mean absorbance values of telomerase activity measured following treatment with some of the above­mentioned formulations were statistically significantly higher compared to those of the untreated cells. In particular, in order of importance with respect to telomerase activation from highest to lowest, 08AGTLF, OA, Nutrient 4, TA­65, MA, Nutrient 3 and Nutrient 2, triggered statistically significant increase in telomerase activity compared to the untreated cells. 08AGTLF reached the highest levels of telomerase activity reported to date, at least to our knowledge, increasing telomerase activity by 8.8 folds compared to untreated cells, while Nutrient 4 and OA were also potent activators (4.3­fold and 5.9­fold increase, respectively). On the whole, this study indicates that the synergistic effect of nutrients and natural compounds can activate telomerase and produce more potent formulations. Human clinical studies using these formulations are required to evaluate their mode of action. This would reveal the health benefits of telomerase activation through natural molecules and would shed new light onto the treatment of aging­related diseases.

Targeted Metabolomic Analysis of Serum Fatty Acids for the Prediction of Autoimmune Diseases.

Autoimmune diseases (ADs) are rapidly increasing worldwide and accumulating data support a key role of disrupted metabolism in ADs. This study aimed to identify an improved combination of Total Fatty Acids (TFAs) biomarkers as a predictive factor for the presence of autoimmune diseases. A retrospective nested case-control study was conducted in 403 individuals. In the case group, 240 patients diagnosed with rheumatoid arthritis, thyroid disease, multiple sclerosis, vitiligo, psoriasis, inflammatory bowel disease, and other AD were included and compared to 163 healthy individuals. Targeted metabolomic analysis of serum TFAs was performed using GC-MS, and 28 variables were used as input for the predictive models. The primary analysis identified 12 variables that were statistically significantly different between the two groups, and metabolite-metabolite correlation analysis revealed 653 significant correlation coefficients with 90% level of significance (p < 0.05). Three predictive models were developed, namely (a) a logistic regression based on Principal Component Analysis (PCA), (b) a straightforward logistic regression model and (c) an Artificial Neural Network (ANN) model. PCA and straightforward logistic regression analysis, indicated reasonably well adequacy (74.7 and 78.9%, respectively). For the ANN, a model using two hidden layers and 11 variables was developed, resulting in 76.2% total predictive accuracy. The models identified important biomarkers: lauric acid (C12:0), myristic acid (C14:0), stearic acid (C18:0), lignoceric acid (C24:0), palmitic acid (C16:0) and heptadecanoic acid (C17:0) among saturated fatty acids, Cis-10-pentadecanoic acid (C15:1), Cis-11-eicosenoic acid (C20:1n9), and erucic acid (C22:1n9) among monounsaturated fatty acids and the Gamma-linolenic acid (C18:3n6) polyunsaturated fatty acid. The metabolic pathways of the candidate biomarkers are discussed in relation to ADs. The findings indicate that the metabolic profile of serum TFAs is associated with the presence of ADs and can be an adjunct tool for the early diagnosis of ADs.

Association of nutraceutical supplements with longer telomere length.

Telomeres are nucleotide tandem repeats located at the tip of eukaryotic chromosomes that maintain genomic integrity. The gradual shortening of telomeres leads to cellular senescence and apoptosis, a key mechanism of aging and age­related chronic diseases. Epigenetic factors, such as nutrition, exercise and tobacco can affect the rate at which telomeres shorten and can modify the risk of developing chronic diseases. In this study, we evaluated the effects of a combination of nutraceutical supplements (NS) on telomere length (TL) in healthy volunteers with no medical history of any disease. Participants (n=47) were selected from healthy outpatients visiting a private clinic and were divided into the experimental group (n=16), that received the NS and the control group (n=31). We estimated the length of single telomeres in metaphase spread leukocytes, isolated from peripheral blood, using quantitative­fluorescent in situ hybridization (Q­FISH) analysis. The length of the whole telomere genome was significantly increased (P<0.05) for the mean, 1st quartile and median measurements in the experimental group. Similar findings were observed for short TL (20th percentile) (P<0.05) for the median and 3rd quartile measurements in the NS group, compared to the control group. The beneficial effects of the supplements on the length of short telomeres remained significant (P<0.05) following adjustment for age and sex. Telomeres were moderately longer in female patients compared to the male patients. On the whole, the findings of this study suggest that the administration of NS may be linked to sustaining the TL.

Application of metabolomics part II: Focus on fatty acids and their metabolites in healthy adults.

Fatty acids (FAs) play critical roles in health and disease. The detection of FA imbalances through metabolomics can provide an overview of an individual's health status, particularly as regards chronic inflammatory disorders. In this study, we aimed to establish sensitive reference value ranges for targeted plasma FAs in a well­defined population of healthy adults. Plasma samples were collected from 159 participants admitted as outpatients. A total of 24 FAs were analyzed using gas chromatography­mass spectrometry, and physiological values and 95% reference intervals were calculated using an approximate method of analysis. The differences among the age groups for the relative levels of stearic acid (P=0.005), the omega­6/omega­3 ratio (P=0.027), the arachidonic acid/eicosapentaenoic acid ratio (P<0.001) and the linoleic acid­produced dihomo­gamma­linolenic acid (P=0.046) were statistically significant. The majority of relative FA levels were higher in males than in females. The levels of myristic acid (P=0.0170) and docosahexaenoic acid (P=0.033) were significantly different between the sexes. The reference values for the FAs examined in this study represent a baseline for further studies examining the reproducibility of this methodology and sensitivities for nutrient deficiency detection and investigating the biochemical background of pathological conditions. The application of these values to clinical practice will allow for the discrimination between health and disease and contribute to early prevention and treatment.

The association of female and male infertility with telomere length (Review).

Telomere length (TL) has long been associated with aging, as telomeres serve as protective caps of chromosomes, and are thus deeply involved in the preservation of genome integrity and are vital to cellular functions. Traditionally, a strong link connects aging and infertility in both sexes, with an earlier onset in females. Over the past decade, telomeres have attracted increasing attention due to the role they play in fertility. In this review, we investigated the potential positive or negative association between relative TL and different factors of female and male infertility. A systematic search of the PubMed database was conducted. Out of the 206 studies identified, 45 were reviewed as they fulfilled the criteria of validity and relevance. Following an analysis and a comparison of the study outcomes, several clear trends were observed. The majority of female infertility factors were associated with a shorter TL, with the exception of endometriosis, premature ovarian failure and clear cell carcinoma that were associated with a longer TL and polycystic ovary syndrome (PCOS), which revealed conflicting results among several studies, leading to ambiguous conclusions. Male infertility factors were associated with a shorter TL. Although this review can provide an outline of general trends in the association of TL with infertility factors, further epidemiological and original research studies are required to focus on investigating the basis of these varying lengths of telomeres.

Improving diagnosis, prognosis and prediction by using biomarkers in CRC patients (Review).

Colorectal cancer (CRC) is among the most common cancers. In fact, it is placed in the third place among the most diagnosed cancer in men, after lung and prostate cancer, and in the second one for the most diagnosed cancer in women, following breast cancer. Moreover, its high mortality rates classifies it among the leading causes of cancer­related death worldwide. Thus, in order to help clinicians to optimize their practice, it is crucial to introduce more effective tools that will improve not only early diagnosis, but also prediction of the most likely progression of the disease and response to chemotherapy. In that way, they will be able to decrease both morbidity and mortality of their patients. In accordance with that, colon cancer research has described numerous biomarkers for diagnostic, prognostic and predictive purposes that either alone or as part of a panel would help improve patient's clinical management. This review aims to describe the most accepted biomarkers among those proposed for use in CRC divided based on the clinical specimen that is examined (tissue, faeces or blood) along with their restrictions. Lastly, new insight in CRC monitoring will be discussed presenting promising emerging biomarkers (telomerase activity, telomere length and micronuclei frequency).