Shortened telomere length in peripheral blood leukocytes is associated with cumulative radioactive iodine doses in patients with differentiated thyroid carcinoma.

BACKGROUND: Telomere length is associated with cancer risk and cancer aggressiveness. Radioactive iodine (RAI) therapy for thyroid cancer has raised concerns for second primary malignancy (SPM) in patients with high cumulative doses. The association between RAI dose and peripheral blood leukocyte telomere length was examined. METHODS: A total of 425 patients were included who underwent total thyroidectomy and were followed up for at least 1 year with or without RAI treatment. The relative telomere length (RTL) of the patients was assessed via a quantitative polymerase chain reaction amplification method. RAI doses were divided into five groups on the basis of cumulative dose, and a comparison was made among these groups. RESULTS: The number of patients with RAI treatment was 287 (67.5%), and the cumulative RAI dose was 3.33 GBq (range, 1.11-131.35 GBq). The mean RTL was significantly shorter in the highest RAI group (>22.2 GBq) compared to both the no-RAI and lower dose groups. The association between RAI dose and RTL was positive in the lower RAI group (1.1-3.7 GBq) and negative in the highest RAI group in both univariate and multivariate analyses. We observed 59 (13.9%) SPMs and 20 (4.7%) mortalities, and RTL did not show a significant risk effect for all-cause, thyroid cancer-specific, or SPM-specific mortality. CONCLUSIONS: In patients with thyroid cancer who underwent total thyroidectomy, peripheral blood leukocyte telomere length exhibited a significant association with cumulative RAI dose higher than 22.2 GBq. These results suggest the possibility of telomere length shortening in patients who undergo high-dose RAI treatment.

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.

Prenatal thyroid hormones accelerate postnatal growth and telomere shortening in wild great tits.

The early-life environment is known to affect later-life health and disease, which could be mediated by the early-life programming of telomere length, a key hallmark of ageing. According to the fetal programming of telomere biology hypothesis, variation in prenatal exposure to hormones is likely to influence telomere length. Yet, the contribution of key metabolic hormones, i.e. thyroid hormones (THs), has been largely ignored. We recently showed that in contrast to predictions, exposure to elevated prenatal THs increased postnatal telomere length in wild collared flycatchers, but the generality of such effect, the underlying proximate mechanisms and consequences for survival have not been investigated. We therefore conducted a comprehensive study evaluating the impact of THs on potential drivers of telomere dynamics (growth, post-natal THs, mitochondria and oxidative stress), telomere length and medium-term survival using wild great tits as a model system. While prenatal THs did not significantly affect telomere length a week after hatching (i.e. day 7), they influenced postnatal telomere shortening (i.e. shorter telomeres at day 14 and the following winter) but not apparent survival. Circulating THs, mitochondrial density or oxidative stress biomarkers were not significantly influenced, whereas the TH-supplemented group showed accelerated growth, which may explain the observed delayed effect on telomeres. We discuss several alternative hypotheses that may explain the contrast with our previous findings in flycatchers. Given that shorter telomeres in early life tend to be carried until adulthood and are often associated with decreased survival prospects, the effects of prenatal THs on telomeres may have long-lasting effects on senescence.

Effect of Omega-3 Fatty Acids on Telomeres-Are They the Elixir of Youth?

Telomeres are complexes consisting of tandem repeat DNA combined with associated proteins that play a key role in protecting the ends of chromosomes and maintaining genome stability. They are considered a biological clock, as they shorten in parallel with aging. Furthermore, short telomeres are associated with several age-related diseases. However, the variability in telomere shortening independent of chronological age suggests that it is a modifiable factor. In fact, it is regulated inter alia by genetic damage, cell division, aging, oxidative stress, and inflammation. A key question remains: how can we prevent accelerated telomere attrition and subsequent premature replicative senescence? A number of studies have explored the possible impact of omega-3 fatty acids on telomere shortening. This review summarizes published cross-sectional studies, randomized controlled trials, and rodent studies investigating the role of omega-3 fatty acids in telomere biology. It also covers a broad overview of the mechanism, currently favored in the field, that explains the impact of omega-3 fatty acids on telomeres-the food compound's ability to modulate oxidative stress and inflammation. Although the results of the studies performed to date are not consistent, the vast majority indicate a beneficial effect of omega-3 fatty acids on telomere length.

Importance of Telomere Shortening in the Pathogenesis of Ulcerative Colitis: A New Treatment From the Aspect of Telomeres in Intestinal Epithelial Cells.

BACKGROUND AND AIMS: Ulcerative colitis [UC] is a chronic inflammatory disease of the colon with frequent relapses. Telomere shortening in intestinal epithelial cells has been reported in severe or longstanding cases. However, its influence on UC pathogenesis remains unelucidated. To this end, we evaluated telomere shortening using a long-term organoid inflammation model that we had originally established. METHODS: A UC model using human colon organoids was established to assess telomere changes chronologically. MST-312 was used for the telomerase inhibition assay. The potential of telomerase activators as a novel UC treatment was evaluated with an in vitro model, including microarray analysis, and histological changes were assessed using xenotransplantation into mouse colonic mucosa. RESULTS: Our UC model reproduced telomere shortening in vitro, which was induced by the continuous suppression of telomerase activity via P53. MST-312-based analysis revealed that telomere shortening was involved in the pathogenesis of UC. Madecassoside [MD] improved the telomere length of the UC model and UC patient-derived organoids, which further promoted cell proliferation in vitro and improved the graft take-rate of xenotransplantation. Moreover, histological analysis revealed that MD induced normal crypt structure with abundant goblet cells. CONCLUSIONS: This study is the first to reveal the mechanism and importance of telomere shortening in the pathogenesis of UC. MD could be a novel candidate for UC treatment beyond endoscopic mucosal healing.

Trends in Natural Nutrients for Oxidative Stress and Cell Senescence.

Due to the increase in the aged population and increased life expectancy, the underlying mechanisms involved in the aging process and cell senescence and the ways for modulating these processes in age-related diseases become important. One of the main mechanisms involved in aging and cell senescence, especially in the diseases related to aging, is the oxidative stress process and the following inflammation. Hence, the effects of antioxidants are highlighted in the literature due to their beneficial impacts on inhibiting telomere shortening or DNA damage and other processes related to aging and cell senescence in age-related diseases. Dietary components, foods, and dietary patterns rich in antioxidants can modulate the aging process and delay the progression of some chronic diseases such as cardiovascular diseases, diabetes, and Alzheimer's disease. Foods high in polyphenols, vitamin C, or carotenoids, olive oil, seeds, nuts, legumes, dietary supplements such as CoQ10, and some other dietary factors are the most important nutritional sources that have high antioxidant contents which can positively affect cell senescence and disease progression. Plant dietary patterns including Mediterranean diets can also inhibit telomere shortening following oxidative damages, and this can delay cell aging and senescence in age-related diseases. Further, olive oil can inhibit protein aggregation in Alzheimer's disease. It can be concluded that nutrition can delay the process of cell senescence in age-related diseases via inhibiting oxidative and inflammatory pathways. However, more studies are needed to better clarify the underlying mechanisms of nutrition and dietary components on cell senescence, aging, and disease progression, especially those related to age.

Folic acid alleviates age-related cognitive decline and inhibits apoptosis of neurocytes in senescence-accelerated mouse prone 8: deoxythymidine triphosphate biosynthesis as a potential mechanism.

Disturbed deoxythymidine triphosphate biosynthesis due to the inhibition of thymidylate synthase (TS) can lead to uracil accumulation in DNA, eventually, lead to neurocytes apoptosis and cognitive decline. Folic acid supplementation delayed cognitive decline and neurodegeneration in senescence-accelerated mouse prone 8 (SAMP8). Whether folic acid, one of nutrition factor, the effect on the expression of TS is unknown. The study aimed to determine if folic acid supplementation could alleviate age-related cognitive decline and apoptosis of neurocytes by increasing TS expression in SAMP8 mice. According to folic acid concentration in diet, four-month-old male SAMP8 mice were randomly divided into three different diet groups by baseline body weight in equal numbers. Moreover, to evaluate the role of TS, a TS inhibitor was injected intraperitoneal. Cognitive test, apoptosis rates of neurocytes, expression of TS, relative uracil level in telomere, and telomere length in brain tissue were detected. The results showed that folic acid supplementation decreased deoxyuridine monophosphate accumulation, uracil misincorporation in telomere, alleviated telomere length shorting, increased expression of TS, then decreased apoptosis rates of neurocytes, and alleviated cognitive performance in SAMP8 mice. Moreover, at the same concentration of folic acid, TS inhibitor raltitrexed increased deoxyuridine monophosphate accumulation, uracil misincorporation in telomere, and exacerbated telomere length shorting, decreased expression of TS, then increased apoptosis rates of neurocytes, and decreased cognitive performance in SAMP8 mice. In conclusion, folic acid supplementation alleviated age-related cognitive decline and inhibited apoptosis of neurocytes by increasing TS expression in SAMP8 mice.

Bovine Colostrum, Telomeres, and Skin Aging.

BACKGROUND: Applied topically, growth factors, cytokines, and other components in bovine colostrum are known to affect collagen biosynthesis, thus offering promise as a therapeutic modality in wound healing, delay in skin aging, and skin rejuvenation. OBJECTIVE: To demonstrate the protective effect that liposomal bovine colostrum exerts on skin aging using telomere length as an aging biomarker. METHODS: Human fibroblasts were cultured for 8 weeks with colostrum at three concentrations (0.125%, 0.25%, 0.50%). Cells were cultured and assayed both under standard conditions, as well as with H2O2 added as an agent of oxidative stress. Alterations in proliferation rates, telomere lengths, and telomere shortening rates (TSRs) were determined in each treatment group and compared. RESULTS: Colostrum increased the proliferation rate of the fibroblast control cells and the addition of H2O2(without colostrum) decreased the proliferation rates of the fibroblast control cells. Under standard culture conditions, telomeres shortened progressively over 8 weeks and the addition of colostrum reduced the rate of telomere shortening. Under oxidative stress conditions (H2O2 – induced) the TSR increased; however, treatment with colostrum appeared to attenuate this increase. CONCLUSIONS: Under normal culture conditions and after both 4 weeks and 8 weeks of treatment, liposomal bovine colostrum appears to exert a protective effect on telomere length erosion. Under culture conditions of oxidative stress and after 8 weeks of treatment, colostrum appears to exert a protective effect on telomere length erosion. These results suggest that topical treatment of the liposomal bovine colostrum formulation would enhance skin health as the skin ages. J Drugs Dermatol. 20(5):538-545. doi:10.36849/JDD.5851.

Telomerase as a Therapeutic Target in Cardiovascular Disease.

Shortened telomeres have been linked to numerous chronic diseases, most importantly coronary artery disease, but the underlying mechanisms remain ill defined. Loss-of-function mutations and deletions in telomerase both accelerate telomere shortening but do not necessarily lead to a clinical phenotype associated with atherosclerosis, questioning the causal role of telomere length in cardiac pathology. The differential extranuclear functions of the 2 main components of telomerase, telomerase reverse transcriptase and telomerase RNA component, offer important clues about the complex relationship between telomere length and cardiovascular pathology. In this review, we critically discuss relevant preclinical models, genetic disorders, and clinical studies to elucidate the impact of telomerase in cardiovascular disease and its potential role as a therapeutic target. We suggest that the antioxidative function of mitochondrial telomerase reverse transcriptase might be atheroprotective, making it a potential target for clinical trials. Graphic Abstract: A graphic abstract is available for this article.

The Association between Antidiabetic Agents and Leukocyte Telomere Length in the Novel Classification of Type 2 Diabetes Mellitus.

AIMS: This study aimed to explore the new role of telomere length (TL) in the novel classification of type 2 diabetes mellitus (T2DM) patients driven by cluster analysis. MATERIALS AND METHODS: A total of 541 T2DM patients were divided into 4 subgroups by k-means analysis: mild obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), and mild age-related diabetes (MARD). After patients with insufficient data were excluded, further analysis was conducted on 246 T2DM patients. The TL was detected using telomere restriction fragment, and the related diabetic indexes were also measured by clinical standard procedures. RESULTS: The MARD group had significantly shorter TLs than the MOD and SIDD groups. Then, we subdivided all T2DM patients into the MARD and NONMARD groups, which included the MOD, SIDD, and SIRD groups. The TLs of the MARD group, associated with age, were discovered to be significantly shorter than those of the NONMARD group (p = 0.0012), and this difference in TL disappeared after metformin (p = 0.880) and acarbose treatment (p = 0.058). The linear analysis showed that metformin can more obviously reduce telomere shortening in the MARD group (r = 0.030, 95% CI 0.010-0.051, p = 0.004), and acarbose can more apparently promote telomere attrition in the SIRD group (r = -0.069, 95% CI -0.100 to -0.039, p< 0.001) compared with other T2DM patients after adjusting for age and gender. CONCLUSIONS: The MARD group was found to have shorter TLs and benefit more from the antiaging effect of metformin than other T2DM. Shorter TLs were observed in the SIRD group after acarbose use.

Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial.

INTRODUCTION: Aging is characterized by the progressive loss of physiological capacity. At the cellular level, two key hallmarks of the aging process include telomere length (TL) shortening and cellular senescence. Repeated intermittent hyperoxic exposures, using certain hyperbaric oxygen therapy (HBOT) protocols, can induce regenerative effects which normally occur during hypoxia. The aim of the current study was to evaluate whether HBOT affects TL and senescent cell concentrations in a normal, non-pathological, aging adult population. METHODS: Thirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures. Whole blood samples were collected at baseline, at the 30th and 60th session, and 1-2 weeks following the last HBOT session. Peripheral blood mononuclear cells (PBMCs) telomeres length and senescence were assessed. RESULTS: Telomeres length of T helper, T cytotoxic, natural killer and B cells increased significantly by over 20% following HBOT. The most significant change was noticed in B cells which increased at the 30th session, 60th session and post HBOT by 25.68%±40.42 (p=0.007), 29.39%±23.39 (p=0.0001) and 37.63%±52.73 (p=0.007), respectively. There was a significant decrease in the number of senescent T helpers by -37.30%±33.04 post-HBOT (P<0.0001). T-cytotoxic senescent cell percentages decreased significantly by -10.96%±12.59 (p=0.0004) post-HBOT. In conclusion, the study indicates that HBOT may induce significant senolytic effects including significantly increasing telomere length and clearance of senescent cells in the aging populations.

Stabilization of telomere by the antioxidant property of polyphenols: Anti-aging potential.

Aging is a form of a gradual loss of physiological integrity that results in impaired cellular function and ultimately increased vulnerability to disease and death. This process is a significant risk factor for critical age-related disorders such as cancer, diabetes, cardiovascular disease, and neurological conditions. Several mechanisms contribute to aging, most notably progressive telomeres shortening, which can be counteracted by telomerase enzyme activity and increasing in this enzyme activity associated with partly delaying the onset of aging. Individual behaviors and environmental factors such as nutrition affect the life-span by impact the telomerase activity rate. Healthy eating habits, including antioxidant intakes, such as polyphenols, can have a positive effect on telomere length by this mechanism. In this review, after studying the underlying mechanisms of aging and understanding the relationships between telomeres, telomerase, and aging, it has been attempted to explain the effect of polyphenols on reversing the oxidative stress and aging process.

Consequences of trace metal cocktail exposure in zebra finch (Taeniopygia guttata) and effect of calcium supplementation.

Trace metal elements are significant stressors in urban areas. Their harmful effects on physiological parameters are demonstrated, but current laboratory studies are not representative of wild chronic exposure to a trace metal cocktail. Calcium can reduce the accumulation and toxicity of several metals, but soil acidification in cities leads to a decrease in bioavailability of this element. The objective of this study was to investigate the accumulation and toxicity of a trace metal cocktail representative of urban exposure on passerine birds, and test the importance of calcium availability on these toxic effects. We exposed zebra finches (Taeniopygia guttata) to a cocktail of seven metals and one metalloid in drinking water, with or without calcium supplementation. We monitored the concentration of metals in the blood and feathers, and their effects on oxidative status and telomere length. The metal cocktail led to higher concentration of all elements in the feathers, and of arsenic and lead in the blood. Birds with a higher concentration of cadmium, arsenic and lead in the feathers had shorter telomeres, but no impact of the cocktail was detected on oxidative status. Birds of the 'calcium' group and the 'calcium and metal' group accumulated higher concentrations of zinc, chromium and nickel in feathers. The 'calcium and metal' group also accumulated lower concentrations of arsenic and lead in feathers compared to the 'metal' group. Our results suggest that chronic exposure to a cocktail of metals at low concentrations has deleterious effects on birds, which can be limited through calcium intake.

Obesity and ageing: Two sides of the same coin.

Conditions and comorbidities of obesity mirror those of ageing and age-related diseases. Obesity and ageing share a similar spectrum of phenotypes such as compromised genomic integrity, impaired mitochondrial function, accumulation of intracellular macromolecules, weakened immunity, shifts in tissue and body composition, and enhanced systemic inflammation. Moreover, it has been shown that obesity reduces life expectancy by 5.8 years in men and 7.1 years in women after the age of 40. Shorter life expectancy could be because obesity holistically accelerates ageing at multiple levels. Besides jeopardizing nuclear DNA and mitochondrial DNA integrity, obesity modifies the DNA methylation pattern, which is associated with epigenetic ageing in different tissues. Additionally, other signs of ageing are seen in individuals with obesity including telomere shortening, systemic inflammation, and functional declines. This review aims to show how obesity and ageing are "two sides of the same coin" through discussing how obesity predisposes an individual to age-related conditions, illness, and disease. We will further demonstrate how the mechanisms that perpetuate the early-onset of chronic diseases in obesity parallel those of ageing.

Protective role of selenium in the shortening of telomere length in newborns induced by in utero heavy metal exposure.

The effects of toxic heavy metals, such as arsenic (As), cadmium (Cd), and lead (Pb), on telomere length (TL) have been reported previously. Although selenium (Se) is considered as an anti-oxidant which may detoxify the effects, there are no data on whether Se could protect against the TL-shortening effects of heavy metals. Thus, the aim of this study was to evaluate the protective role of Se against heavy metal-induced TL shortening. A birth cohort study was conducted in Myanmar in 2016, including 408 mother-infant pairs. First, pregnant women in the third trimester were interviewed concerning their socioeconomic, and pregnancy and birth characteristics using a pre-validated questionnaire. Maternal spot urine samples were collected after the interview. During the follow-up period (1-3 months), blood samples were collected from the umbilical cord at birth by local health workers. Metal concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). TL was measured by quantitative real-time polymerase chain reaction (PCR). Relative TL was calculated as the ratio of telomere genes to single-copy genes. To evaluate the effect of Se on TL shortening, molar ratios were calculated. Linear regression analyses were performed to examine the associations between heavy metals and TL, individually and after adjustment for Se level. The effects of As, Cd, and Pb exposure on TL were smaller after adjustment for the Se level, especially for Pb (unadjusted ß = -0.10; 95% CI: 0.18, -0.01; adjusted ß = -0.03; 95% CI: 0.13, 0.05). On stratifying the data by Se concentration, there was no significant association between Cd or Pb exposure and TL in the high-Se group. Our study indicated a protective effect of Se against the TL shortening induced by heavy metal exposure, where the effect sizes were smaller after adjusting for the Se level, compared to individual metal exposure.

Antioxidant supplementation slows telomere shortening in free-living white stork chicks.

Telomere length (TL) and shortening is increasingly shown to predict variation in survival and lifespan, raising the question of what causes variation in these traits. Oxidative stress is well known to accelerate telomere attrition in vitro, but its importance in vivo is largely hypothetical. We tested this hypothesis experimentally by supplementing white stork (Ciconia ciconia) chicks with antioxidants. Individuals received either a control treatment, or a supply of tocopherol (vitamin E) and selenium, which both have antioxidant properties. The antioxidant treatment increased the concentration of tocopherol for up to two weeks after treatment but did not affect growth. Using the telomere restriction fragment technique, we evaluated erythrocyte TL and its dynamics. Telomeres shortened significantly over the 21 days between the baseline and final sample, independent of sex, mass, size and hatching order. The antioxidant treatment significantly mitigated shortening rate of average TL (-31% in shorter telomeres; percentiles 10th, 20th and 30th). Thus, our results support the hypothesis that oxidative stress shortens telomeres in vivo.

Effect of antioxidants, mitochondrial cofactors and omega-3 fatty acids on telomere length and kinematic joint mobility in young and old shepherd dogs - A randomized, blinded and placebo-controlled study.

In dogs, decreasing telomere length is a biomarker for cellular aging. On a systemic level, aging affects the locomotor system in particular, leading to restricted joint mobility. As aging is thought to be related to oxidative stress, it may be counteracted by a diet enriched with antioxidants, mitochondrial cofactors and omega-3 fatty acids. This randomized, blinded and placebo-controlled study examined the influence of an accordingly enriched diet compared to a control diet on 36 young and 38 old shepherd dogs. At the outset, after 3 and after 6 months, mean and minimum telomere lengths were measured. Furthermore, minimum and maximum joint angles and range of motion of the shoulder, elbow, carpal, hip, stifle and tarsal joints were measured by computer-assisted gait analysis. A positive influence of the enriched diet on old dogs could be verified for minimum telomere length and all three parameters of the shoulder joint on the side with the higher vertical ground reaction force after 6 months. In the other joints there were less significant differences; in some cases they indicated a contrary influence of the enriched diet on young dogs, probably due to its reduced protein content. The greater effect of the enriched diet on minimum than on mean telomere length may be due to the higher preference of telomerase for short telomeres. The greater effect on shoulder joint mobility is explained by the greater influence of musculature and connective tissue in this joint. For elderly dogs it is advisable to feed these nutritional supplements.

The Psilocybin-Telomere Hypothesis: An empirically falsifiable prediction concerning the beneficial neuropsychopharmacological effects of psilocybin on genetic aging.

We introduce a novel hypothesis which states that the therapeutic utilisation of psilocybin has beneficial effects on genetic aging. Ex hypothesi, we predict a priori that controlled psilocybin interventions exert quantifiable positive impact on leucocyte telomere length (telomeres are a robust predictor of mortality and multifarious aging-related diseases). Our hypothesising follows the Popperian logic of scientific discovery, viz., bold (and refutable) conjectures form the very foundation of scientific progress. The 'psilocybin-telomere hypothesis' is formalised as a logically valid deductive (syllogistic) argument and we provide substantial evidence to support the underlying premises. Impetus for our theorising derives from a plurality of converging empirical sources indicating that psilocybin has persistent beneficial effects on various aspects of mental health (e.g., in the context of depression, anxiety, PTSD, OCD, addiction, etc.). Additional support is based on a large corpus of studies that establish reliable correlations between mental health and telomere attrition (improved mental health is generally correlated with longer telomeres). Another pertinent component of our argument is based on recent studies which demonstrate that "meditative states of consciousness" provide beneficial effects on genetic aging. Similarly, psilocybin can induce states of consciousness that are neurophysiologically and phenomenologically significantly congruent with meditative states. Furthermore, prior research has demonstrated that a single dose of psilocybin can occasion life-changing transformative experiences (≈ 70% of healthy volunteers rate their experience with psilocybin amongst the five personally most meaningful lifetime events, viz., ranked next to giving birth to a child or losing a loved one). We postulate that these profound psychological events leave quantifiable marks at the molecular genetic/epigenetic level. Given the ubiquitous availability and cost effectiveness of telomere length assays, we suggest that quantitative telomere analysis should be regularly included in future psilocybin studies as an adjunctive biological marker (i.e., to facilitate scientific consilience via methodological triangulation). In order to substantiate the 'psilocybin-telomere hypothesis' potential neuropsychopharmacological, endocrinological, and genetic mechanisms of action are discussed (e.g., HPA-axis reactivity, hippocampal neurogenesis, neurotropic growth factors such as BDNF, 5-HT2A receptor agonism, neuroplasticity/synaptoplasticity, brain-wide alterations in neuronal functional connectivity density, involvement of the SLC6A4 serotonin transporter gene, inter alia). The proposed research agenda is thus intrinsically highly interdisciplinary, and it has deep ramifications from a philosophy of science perspective as it connects the epistemic level (qualitative experiential phenomenology) with the ontic level (quantitative molecular genetics) of analysis. In the long term, multidisciplinary and innovative investigations of the 'psilocybin-telomere hypothesis' could contribute to the improvement of senotherapeutic psychological interventions and the identification of novel geroprotective and neuroprotective/restorative pharmaceutical targets to decelerate genetic aging and improve well-being and quality of life during the aging process.

Leukocyte telomere length and serum polyunsaturated fatty acids, dietary habits, cardiovascular risk factors and features of myocardial infarction in elderly patients.

BACKGROUND: Telomeres are non-coding sequences at the end of eukaryote chromosomes, which in complex with associated proteins serve to protect subtelomeric DNA. Telomeres shorten with each cell division, are regarded as a biomarker for aging and have also been suggested to play a role in atherosclerosis and cardiovascular disease (CVD). The aim of the present study was to explore the associations between leukocyte telomere length and serum polyunsaturated fatty acids, diet, cardiovascular risk factors and features of myocardial infarction (MI) in elderly patients. METHODS: The material is based upon the first 299 included patients in the OMEMI trial, where patients aged 70-82 years of age are randomized to receive omega-3 supplements or corn oil (placebo) after MI. Patients were included 2-8 weeks after the index MI. DNA was extracted from whole blood, and leukocyte telomere length (LTL) was analyzed by qPCR and reported as a number relative to a reference gene. Serum long chain polyunsaturated fatty acid (LCPUFA) content was analyzed by gas chromatography. Diet was evaluated with the validated SmartDiet food frequency questionnaire. Medical records, patient interviews and clinical examination provided previous medical history and anthropometric data. Non-parametric statistical tests were used. RESULTS: Median (25, 75 percentile) LTL was 0.55 (0.42, 0.72). Patients had a median age of 75 years, 70.2% were male and 45.2% used omega-3 supplements. There was a weak, but significant correlation between LTL and linoleic acid (r = 0.139, p = 0.017), but not with other LCPUFAs. There was a trend towards longer telomeres with a healthier diet, but this did not reach statistical significance (p = 0.073). No associations were found between LTL and CVD risk factors or features of MI. CONCLUSIONS: In our population of elderly with a recent myocardial infarction LTL was associated with linoleic acid concentrations, but not with other LCPUFAs. Patients with a healthy diet tended to have longer telomeres. The limited associations may be due to age and the narrow age-span in our population. Further studies, designed to detect longitudinal changes should be performed to explore the role of telomeres in cardiovascular aging. TRIAL REGISTRATION: Clinical trials no. NCT01841944, registration date April 29, 2013.