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1.
DNA Res ; 31(3)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38600880

ABSTRACT

We report the complete telomere-to-telomere genome assembly of Oldenlandia diffusa which renowned in traditional Chinese medicine, comprising 16 chromosomes and spanning 499.7 Mb. The assembly showcases 28 telomeres and minimal gaps, with a total of only five. Repeat sequences constitute 46.41% of the genome, and 49,701 potential protein-coding genes have been predicted. Compared with O. corymbosa, O. diffusa exhibits chromosome duplication and fusion events, diverging 20.34 million years ago. Additionally, a total of 11 clusters of terpene synthase have been identified. The comprehensive genome sequence, gene catalog, and terpene synthase clusters of O. diffusa detailed in this study will significantly contribute to advancing research in this species' genetic, genomic, and pharmacological aspects.


Subject(s)
Genome, Plant , Telomere , Telomere/genetics , Alkyl and Aryl Transferases/genetics , Chromosome Duplication
2.
Cardiovasc Diabetol ; 23(1): 98, 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38493287

ABSTRACT

BACKGROUND: Telomere Length (TL), a marker of cellular aging, holds promise as a biomarker to elucidate the molecular mechanism of diabetes. This study aimed to investigate whether shorter telomeres are associated with a higher risk of type 2 diabetes mellitus (T2DM) incidence in patients with coronary heart disease; and to determine whether the most suitable dietary patterns, particularly a Mediterranean diet or a low-fat diet, can mitigate the development of diabetes in these patients after a follow-up period of five years. METHODS: The CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study) was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive two healthy diets. Clinical investigators were masked to treatment assignment; participants were not. Quantitative-PCR was used to assess TL measurements. FINDINGS: 1002 patients (59.5 ± 8.7 years and 82.5% men) were enrolled into Mediterranean diet (n = 502) or a low-fat diet (n = 500) groups. In this analysis, we included all 462 patients who did not have T2DM at baseline. Among them, 107 patients developed T2DM after a median of 60 months. Cox regression analyses showed that patients at risk of short telomeres (TL < percentile 20th) are more likely to experience T2DM than those at no risk of short telomeres (HR 1.65, p-value 0.023). In terms of diet, patients at high risk of short telomeres had a higher risk of T2DM incidence after consuming a low-fat diet compared to patients at no risk of short telomeres (HR 2.43, 95CI% 1.26 to 4.69, p-value 0.008), while no differences were observed in the Mediterranean diet group. CONCLUSION: Patients with shorter TL presented a higher risk of developing T2DM. This association could be mitigated with a specific dietary pattern, in our case a Mediterranean diet, to prevent T2DM in patients with coronary heart disease. TRIAL REGISTRATION: Clinicaltrials.gov number NCT00924937.


Subject(s)
Cardiovascular Diseases , Coronary Disease , Diabetes Mellitus, Type 2 , Diet, Mediterranean , Female , Humans , Male , Biomarkers , Cardiovascular Diseases/epidemiology , Coronary Disease/diagnosis , Coronary Disease/epidemiology , Coronary Disease/genetics , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , Telomere , Young Adult , Adult , Middle Aged , Aged
3.
Aging (Albany NY) ; 16(6): 5711-5739, 2024 03 26.
Article in English | MEDLINE | ID: mdl-38535988

ABSTRACT

BACKGROUND: Observational studies have previously shown a possible link between fatty acids and aging-related diseases, raising questions about its health implications. However, the causal relationship between the two remains uncertain. METHODS: Univariable and multivariable Mendelian randomization (MR) was used to analyze the relationship between five types of fatty acids-polyunsaturated fatty acid (PUFA), monounsaturated fatty acid (MUFA), saturated fatty acid (SFA), Omega-6 fatty acid (Omega-6 FA), and Omega-3 fatty acid (Omega-3 FA) and three markers of aging: telomere length (TL), frailty index (FI), and facial aging (FclAg). The primary approach for Mendelian randomization (MR) analysis involved utilizing the inverse variance weighted (IVW) method, with additional supplementary methods employed. RESULTS: Univariate MR analysis revealed that MUFA, PUFA, SFA, and Omega-6 fatty acids were positively associated with TL (MUFA OR: 1.019, 95% CI: 1.006-1.033; PUFA OR: 1.014, 95% CI: 1.002-1.026; SFA OR: 1.016, 95% CI: 1.002-1.031; Omega-6 FAs OR=1.031, 95% CI: 1.006-1.058). PUFA was also associated with a higher FI (OR: 1.033, 95% CI: 1.009-1.057). In multivariate MR analysis, after adjusting for mutual influences among the five fatty acids, MUFA and PUFA were positively independently associated with TL (MUFA OR: 1.1508, 95% CI = 1.0724-1.2350; PUFA OR: 1.1670, 95% CI = 1.0497-1.2973, while SFA was negatively correlated (OR: 0.8005, 95% CI: 0.7045-0.9096). CONCLUSIONS: Our research presents compelling evidence of a causal association between certain fatty acids and indicators of the aging process. In particular, MUFA and PUFA may play a role in slowing down the aging process, while SFAs may contribute to accelerated aging. These findings could have significant implications for dietary recommendations aimed at promoting healthy aging.


Subject(s)
Fatty Acids, Omega-3 , Fatty Acids , Dietary Fats , Mendelian Randomization Analysis , Fatty Acids, Unsaturated , Fatty Acids, Monounsaturated
4.
Cancer ; 130(12): 2215-2223, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38376914

ABSTRACT

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.


Subject(s)
Iodine Radioisotopes , Leukocytes , Telomere , Thyroid Neoplasms , Thyroidectomy , Humans , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/blood , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Iodine Radioisotopes/therapeutic use , Male , Female , Middle Aged , Adult , Leukocytes/radiation effects , Aged , Telomere/radiation effects , Telomere Shortening/radiation effects , Young Adult , Neoplasms, Second Primary/blood , Adolescent
5.
Environ Res ; 248: 118355, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38295973

ABSTRACT

INTRODUCTION: Placental function is essential for fetal development, but it may be susceptible to malnutrition and environmental stressors. OBJECTIVE: To assess the impact of toxic and essential trace elements in placenta on placental function. METHODS: Toxic metals (cadmium, lead, mercury, cobalt) and essential elements (copper, manganese, zinc, selenium) were measured in placenta of 406 pregnant women in northern Sweden using ICP-MS. Placental weight and birth weight were obtained from hospital records and fetoplacental weight ratio was used to estimate placental efficiency. Placental relative telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) were determined by quantitative PCR (n = 285). Single exposure-outcome associations were evaluated using linear or spline regression, and joint associations and interactions with Bayesian kernel machine regression (BKMR), all adjusted for sex, maternal smoking, and age or BMI. RESULTS: Median cadmium, mercury, lead, cobalt, copper, manganese, zinc, and selenium concentrations in placenta were 3.2, 1.8, 4.3, 2.3, 1058, 66, 10626, and 166 µg/kg, respectively. In the adjusted regression, selenium (>147 µg/kg) was inversely associated with placental weight (B: -158; 95 % CI: -246, -71, per doubling), as was lead at low selenium (B: -23.6; 95 % CI: -43.2, -4.0, per doubling). Manganese was positively associated with placental weight (B: 41; 95 % CI: 5.9, 77, per doubling) and inversely associated with placental efficiency (B: -0.01; 95 % CI: -0.019, -0.004, per doubling). Cobalt was inversely associated with mtDNAcn (B: -11; 95 % CI: -20, -0.018, per doubling), whereas all essential elements were positively associated with mtDNAcn, individually and joint. CONCLUSION: Among the toxic metals, lead appeared to negatively impact placental weight and cobalt decreased placental mtDNAcn. Joint essential element concentrations increased placental mtDNAcn. Manganese also appeared to increase placental weight, but not birth weight. The inverse association of selenium with placental weight may reflect increased transport of selenium to the fetus in late gestation.


Subject(s)
Mercury , Selenium , Trace Elements , Pregnancy , Female , Humans , Placenta , Copper , Manganese , Cadmium , Bayes Theorem , Zinc , Birth Weight , Cobalt , DNA, Mitochondrial
6.
J Ethnopharmacol ; 323: 117694, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38163559

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The Bazhen decoction is one of the most extensively used Traditional Chinese medicine (TCM) prescriptions for treatment of aging related diseases. However, due to the complexity of the components, the pharmacological mechanism of Bazhen decoction is still limited. AIM OF THE STUDY: In this study, with the aim of helping the clinical precision medicine of TCM, we try out a systematic analysis for dissecting the molecular mechanism of complicated TCM prescription: Bazhen decoction. We identify the pharmacological mechanism of Bazhen decoction in telomere elongation as revealed by systematic analysis. MATERIALS AND METHODS: By RNA sequencing and transcriptome analysis of Bazhen decoction treated wild type cells, we reveal the transcriptome profile induced by Bazhen decoction. We utilized the cells derived from Werner syndrome (WS) mice, which is known to be dysfunctional in telomere elongation due to the deficiency of DNA helicase Wrn. By Western blot, qPCR, Immunofluorescence, flow cytometry, telomere FISH, and SA-ß-Gal staining, we verify the transcriptome data and confirm the pharmacological function of Bazhen decoction and its drug containing serum in telomere elongation and reversing progeroid cell senescence. RESULTS: We reveal that Bazhen decoction may systematically regulate multiple anti-aging pathways, including stem cell regulation, protein homeostasis, cardiovascular function, neuronal function, anti-inflammation, anti-DNA damage induced stress, DNA helicase activity and telomere lengthening. We find that Bazhen decoction and its drug containing serum could up-regulate multiple DNA helicases and telomere regulating proteins. The increased DNA helicases promote the resolving of G-quadruplex (G4) structures, and facilitate DNA replication and telomere elongation. These improvements also endow the cellular resistance to DNA damages induced by replication stress, and rescue the WS caused cellular senescence. CONCLUSIONS: Together these data suggest that Bazhen decoction up-regulate the expression of DNA helicases, thus facilitate G4 resolving and telomere maintenance, which rescue the progeroid cellular senescence and contribute to its anti-aging properties. Our data reveal a new molecular mechanism of Bazhen decoction in anti-aging related diseases via elongating telomere, this may shed light in the application of Bazhen decoction in multiple degenerative diseases caused by telomere erosion.


Subject(s)
Werner Syndrome , Animals , Mice , Werner Syndrome/genetics , DNA Damage , Telomere , Cellular Senescence , DNA Helicases/genetics
7.
Eur J Nutr ; 63(1): 291-302, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37870657

ABSTRACT

PURPOSE: Oxidative stress has been reported to cause telomere attrition, which triggers cell apoptosis. Apoptosis of neurocytes may play an essential role in the pathogenesis of neurodegenerative diseases. This study hypothesized that folic acid (FA) supplementation decreased neurocyte apoptosis by alleviating oxidative stress-induced telomere attrition in 25-month-old Sprague Dawley (SD) rats. METHODS: Three-month-old male SD rats were randomly divided into four diet groups by different concentrations of folic acid in equal numbers, with intervention for 22 months. Folate, homocysteine (Hcy), reactive oxygen species (ROS) levels, antioxidant activities, and telomere length in the brain tissues were tested at 11, 18, and 22 months of intervention, and 8-hydroxy-deoxyguanosine (8-OHdG) levels, neurocyte apoptosis and telomere length in the cerebral cortex and hippocampal regions were tested during the 22-month intervention. An automated chemiluminescence system, auto-chemistry analyzer, Q-FISH, qPCR, and TUNEL assay were used in this study. RESULTS: The rats had lower folate concentrations and higher Hcy, ROS, and 8-OHdG concentrations in brain tissue with aging. However, FA supplementation increased folate concentrations and antioxidant activities while decreasing Hcy, ROS, and 8-OHdG levels in rat brain tissue after 11, 18, and 22 months of intervention. Furthermore, FA supplementation alleviated telomere length shortening and inhibited neurocyte apoptosis during the 22-month intervention. CONCLUSION: FA supplementation alleviated oxidative stress-induced telomere attrition and inhibited apoptosis of neurocytes in 25-month-old rats.


Subject(s)
Antioxidants , Folic Acid , Rats , Male , Animals , Folic Acid/pharmacology , Antioxidants/pharmacology , Reactive Oxygen Species , Rats, Sprague-Dawley , Oxidative Stress , Apoptosis , 8-Hydroxy-2'-Deoxyguanosine , Telomere
8.
J Nutr ; 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37918674

ABSTRACT

BACKGROUND: Vitamin B12 is essential for deoxyribonucleic acid synthesis and genome stability. A deficiency of vitamin B12 is associated with telomere shortening, genomic aging, and increased risk of chronic disease and mortality. OBJECTIVES: The study aims to determine the effect of vitamin B12 supplementation on leukocyte telomere length (LTL) in infants at risk of vitamin B12 deficiency. METHODS: The study was a predefined secondary analysis of a randomized controlled trial enrolling 600 Nepalese infants aged 6 -11 mo, who were supplemented with 2 µg (2-3 recommended daily allowances) vitamin B12 or placebo daily for 1 y. At the end of the study, LTL was measured in 497 participants. Mean LTL was compared between the treatment arms in the full sample and predefined subgroups based on markers of vitamin B12 status, hemoglobin, sex, and growth indices. RESULTS: LTL at end-study did not differ between the vitamin B12 and placebo arm with a standardized mean difference (95% confidence interval) of 0.04 (-0.14, 0.21). There was no effect of vitamin B12 on LTL in any of the subgroups. CONCLUSIONS: Providing daily vitamin B12 for 1 y during infancy in a population at risk of vitamin B12 deficiency does not affect LTL. This trial was registered at clinicaltrials.gov as NCT02272842.

9.
Mol Med Rep ; 28(6)2023 Dec.
Article in English | MEDLINE | ID: mdl-37921058

ABSTRACT

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.


Subject(s)
Telomerase , Rats , Animals , Telomerase/metabolism , Leukocytes, Mononuclear/metabolism , Telomere Shortening , Dietary Supplements , Telomere/metabolism
10.
Cureus ; 15(9): e46130, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37900433

ABSTRACT

Mindfulness practices have demonstrated the potential to positively impact various aspects of human health associated with telomere length (TL) - a recognized marker of healthy aging and susceptibility to age-related diseases. This review seeks to conduct an in-depth comparative analysis, examining methodological variations, outcome assessments, strengths, weaknesses, and gaps across mindfulness-focused studies concerning TL and attrition rates. While emerging data tentatively suggest a positive connection between mindfulness practices and TL, a notable research gap pertains to establishing the clinically recommended dosage of yoga/meditation and mindfulness interventions to effectively influence TL. To address this gap, upcoming research should prioritize meticulous structuring, pedagogical precision, and vigilant monitoring of mindfulness interventions to yield psychological and physiological benefits across an appropriate timeframe and intensity. The amalgamation of yoga/meditation or mindfulness emerges as a promising avenue for enhancing the quality of life while counteracting the influence of telomere attrition in the spectrum of age-related diseases. The core objective of this review is to meticulously investigate the interplay between yoga/meditation and mindfulness practices and their potential impact on TL - an essential biomarker indicative of age-related health and well-being. To achieve this, our study methodically compares various methodological approaches, outcome measures, strengths, and limitations within relevant research endeavors focused on TL and attrition rates. Through this scrutiny, we highlight prevailing research gaps. Our analysis underscores the need for comprehensive research efforts aimed at establishing the optimal therapeutic regimen for yielding significant clinical effects on TL and overall health. In summation, our exploration emphasizes the urgency of further studies to unravel the most effective approaches for positively influencing TL and its implications for holistic health.

11.
Nutrients ; 15(19)2023 Oct 09.
Article in English | MEDLINE | ID: mdl-37836587

ABSTRACT

This study examined the association between folic acid supplements (FAs) during different periods of pregnancy and offspring telomere length (TL) at age four in 666 children from the INMA study. FAs were self-reported using food-structured questionnaires during three periods of pregnancy (the first three months of pregnancy, from month fourth onward, and the whole pregnancy). For each period, the average daily dosage of FAs was categorised into (i) <400 µg/d, (ii) ≥400 to 999 µg/d, (iii) ≥1000 to 4999 µg/d, and (iv) ≥5000 µg/d. Leucocyte TL at age four was measured using quantitative PCR methods. Multiple robust linear log-level regression models were used to report the % difference among FA categories. During the first period, and compared with children whose mothers were classified in the reference group (<400 µg/d), children whose mothers took higher dosages of FAs showed shorter TL at age four (≥5000 µg/d). When the first and the second periods were mutually adjusted, children whose mothers self-reported ≥5000 µg/d during the first period of pregnancy had a statistically significant shorter TL than their counterparts (% difference: -7.28% [95% CI: -14.42 to -0.13]). Similar trends were observed for the whole period of pregnancy. When the analysis was stratified by sex, the association was more evident in boys (% difference: -13.5% [95% CI: -23.0 to -4.04]), whereas no association was observed in girls. This study suggests that high dosages of FAs in the first pregnancy period may be associated with a shorter TL in children at age four, particularly among boys. Further studies should confirm these results.


Subject(s)
Dietary Supplements , Folic Acid , Male , Pregnancy , Female , Humans , Child , Cohort Studies , Surveys and Questionnaires , Telomere
12.
J Nutr Health Aging ; 27(8): 609-616, 2023.
Article in English | MEDLINE | ID: mdl-37702332

ABSTRACT

OBJECTIVES: Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio). DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: Participants were Australians aged 60-84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation. RESULTS: The mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was -0.001 (95% CI -0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration. CONCLUSION: In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length.


Subject(s)
Vitamin D , Vitamins , Humans , Aged , Australia , Vitamins/pharmacology , Vitamins/therapeutic use , Calcifediol , Telomere , Dietary Supplements , Randomized Controlled Trials as Topic
13.
Drug Metab Pers Ther ; 38(3): 211-226, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37708954

ABSTRACT

INTRODUCTION: Medicinal plants and herbs are the most important part of the Ayurveda. The term Rasayana in Charaka Samhita confers long life, youthfulness, strong body, freedom from diseases and the plants mentioned in Rsayana possess antiaging property. Aging is the collective term used for the complex detrimental physiological changes that reduce the functional ability of the cell. Oxidative stress, telomeres shortening, inflammation, and mitochondrial dysfunction are the main factors that regulate the aging process. Chronological aging is an irreversible process but the factors causing biological aging can be controlled. Ayurvedic herbs are better for the management of age-related problems. There are several natural bioactive agents present in plants that can delay the aging process in humans. They trigger actions like enhancing gene longevity and telomerase activity, ROS scavenging furthermore regeneration of tissues. CONTENT: The plants mentioned in the Rasayana of Ayurveda have antiaging potential and can be used to solve modern problems related to aging. Some Ayurvedic plants and their antiaging potential has explained in this review. The main causes of aging, medicinal plants and their use as potential antiaging mediator are covered in this study. SUMMARY: The process of aging is still an enigma. It is a complex, irretrievable, dynamic process that involves a number of factors and is subject to a number of environmental and genetic influences. Rasayana aspect has not been much investigated in clinical trials. Aging is considered to result from free radical damage. According to Charaka, Rasayana drugs open the partially or fully blocked channels. Many Rasayanas show free radical scavenging activity and has the potential to mitigate the effects of aging. It gives an overview of the significance of Ayurvedic medicinal plants as a source of inspiration and the use of these plants as remedies for antiaging. OUTLOOK: This study briefly outlooks the causes of aging and how medicinal plants can be used to reverse the aging process. In this study, we discussed the antiaging potential and mechanistic roles of Ayurvedic herbs. These herbs have the properties to slow down the natural process of aging and can successfully manage common age-related problems.


Subject(s)
Aging , Oxidative Stress , Humans
14.
J Dairy Sci ; 106(12): 9822-9842, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37641324

ABSTRACT

The current study was conducted to examine the effect of l-carnitine (LC) supplementation on telomere length and mitochondrial DNA copy number (mtDNAcn) per cell in mid-lactation cows challenged by lipopolysaccharide (LPS) in blood and liver. The mRNA abundance of 31 genes related to inflammation, oxidative stress, and the corresponding stress response mechanisms, the mitochondrial quality control and the protein import system, as well as the phosphatidylinositol 3-kinase/protein kinase B pathway, were assessed using microfluidics integrated fluidic circuit chips (96.96 dynamic arrays). In addition to comparing the responses in cows with or without LC, our objectives were to characterize the oxidative and inflammatory status by assessing the circulating concentration of lactoferrin (Lf), haptoglobin (Hp), fibrinogen, derivates of reactive oxygen metabolites (dROM), and arylesterase activity (AEA), and to extend the measurement of Lf and Hp to milk. Pluriparous Holstein cows were assigned to either a control group (CON, n = 26) or an LC-supplemented group (CAR; 25 g LC/cow per day; d 42 ante partum to d 126 postpartum (PP), n = 27). On d 111 PP, each cow was injected intravenously with LPS (Escherichia coli O111:B4, 0.5 µg/kg). The mRNA abundance was examined in liver biopsies of d -11 and +1 relative to LPS administration. Plasma and milk samples were frequently collected before and after the challenge. After LPS administration, circulating plasma fibrinogen and serum dROM concentrations increased, whereas AEA decreased. Moreover, serum P4 initially increased by 3 h after LPS administration and declined thereafter irrespective of grouping. The Lf concentrations increased in both groups after LPS administration, with the CAR group showing greater concentrations in serum and milk than the CON group. After LPS administration, telomere length in blood increased, whereas mtDNAcn per cell decreased; however, both remained unaffected in liver. For mitochondrial protein import genes, the hepatic mRNA abundance of the translocase of the mitochondrial inner membrane (TIM)-17B was increased in CAR cows. Moreover, TIM23 increased in both groups after LPS administration. Regarding the mRNA abundance of genes related to stress response mechanisms, 7 out of 14 genes showed group × time interactions, indicating a (local) protective effect due to the dietary LC supplementation against oxidative stress in mid-lactating dairy cows. For mtDNAcn and telomere length, the effects of the LPS-induced inflammation were more pronounced than the dietary supplementation of LC. Dietary LC supplementation affected the response to LPS primarily by altering mitochondrial dynamics. Regarding mRNA abundance of genes related to the mitochondrial protein import system, the inner mitochondrial membrane translocase (TIM complex) seemed to be more sensitive to dietary LC than the outer mitochondrial membrane translocase (TOM complex).


Subject(s)
Cattle Diseases , Lactation , Female , Cattle , Animals , Lactation/physiology , Lipopolysaccharides/adverse effects , Carnitine/metabolism , DNA, Mitochondrial , DNA Copy Number Variations , Mitochondrial Dynamics , Inflammation/veterinary , Dietary Supplements , Liver/metabolism , Milk/metabolism , Diet/veterinary , Gene Expression , Fibrinogen/adverse effects , Fibrinogen/metabolism , RNA, Messenger/metabolism , Mitochondrial Proteins/metabolism , Telomere , Cattle Diseases/metabolism
15.
Adv Nutr ; 14(6): 1337-1358, 2023 11.
Article in English | MEDLINE | ID: mdl-37573943

ABSTRACT

Accumulation of deoxyribonucleic acid (DNA) damage diminishes cellular health, increases risk of developmental and degenerative diseases, and accelerates aging. Optimizing nutrient intake can minimize accrual of DNA damage. The objectives of this review are to: 1) assemble and systematically analyze high-level evidence for the effect of supplementation with micronutrients and phytochemicals on baseline levels of DNA damage in humans, and 2) use this knowledge to identify which of these essential micronutrients or nonessential phytochemicals promote DNA integrity in vivo in humans. We conducted systematic literature searches of the PubMed database to identify interventional, prospective, cross-sectional, or in vitro studies that explored the association between nutrients and established biomarkers of DNA damage associated with developmental and degenerative disease risk. Biomarkers included lymphocyte chromosome aberrations, lymphocyte and buccal cell micronuclei, DNA methylation, lymphocyte/leukocyte DNA strand breaks, DNA oxidation, telomere length, telomerase activity, and mitochondrial DNA mutations. Only randomized, controlled interventions and uncontrolled longitudinal intervention studies conducted in humans were selected for evaluation and data extraction. These studies were ranked for the quality of their study design. In all, 96 of the 124 articles identified reported studies that achieved a quality assessment score ≥ 5 (from a maximum score of 7) and were included in the final review. Based on these studies, nutrients associated with protective effects included vitamin A and its precursor ß-carotene, vitamins C, E, B1, B12, folate, minerals selenium and zinc, and phytochemicals such as curcumin (with piperine), lycopene, and proanthocyanidins. These findings highlight the importance of nutrients involved in (i) DNA metabolism and repair (folate, vitamin B12, and zinc) and (ii) prevention of oxidative stress and inflammation (vitamins A, C, E, lycopene, curcumin, proanthocyanidins, selenium, and zinc). Supplementation with certain micronutrients and their combinations may reduce DNA damage and promote cellular health by improving the maintenance of genome integrity.


Subject(s)
Curcumin , Proanthocyanidins , Selenium , Humans , Prospective Studies , Lycopene , Cross-Sectional Studies , Curcumin/pharmacology , Randomized Controlled Trials as Topic , Vitamins/pharmacology , Vitamin A , Micronutrients/pharmacology , Folic Acid/pharmacology , Zinc/pharmacology , Beverages , Phytochemicals/pharmacology , DNA , DNA Damage , Biomarkers , Dietary Supplements
16.
Integr Cancer Ther ; 22: 15347354231154267, 2023.
Article in English | MEDLINE | ID: mdl-37615075

ABSTRACT

A 4-year prospective cohort study on patients with lung, gastric, hepatic, colorectal, breast, uterine, and ovarian cancer was conducted at the East-West Cancer Center (EWCC) of Daejeon Korean Medicine Hospital in Daejeon, Korea. We divided patients into 2 groups based on how long they had been receiving TKM oncotherapy and compared event-free survival (EFS), telomere length change, and quality of life (QoL). The study collected data on 83 patients from October 2016 to June 2020 and discovered no statistical differences in EFS based on the duration of TKM oncotherapy. In the analysis of changes in QoL outcomes, there were no statistically significant group differences between the groups. After controlling for covariates that could affect telomere length, the long-term TKM oncotherapy group had a higher daily telomere attrition rate. The study of the relationship between telomere length and prognostic factors discovered that patients with advanced N stage at the time of diagnosis and who had previously received radiotherapy had shorter telomere length. When examining associations between SNP genotype and percentile score of telomere length, this study was able to confirm an association between telomere length and rs4387287. This study is significant because it is the first to assess the effects of TKM oncotherapy and investigate telomere length-related factors. To assess the effects of TKM oncotherapy on cancer patients' survival and QoL, a longer-term observational study with a larger sample size is required.


Subject(s)
Medicine, Korean Traditional , Quality of Life , Female , Humans , Prospective Studies , Progression-Free Survival , Telomere/genetics , Republic of Korea
17.
J Med Food ; 26(8): 580-585, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37477674

ABSTRACT

Royal jelly (RJ) is a natural bee product that has been used for therapeutic purposes since ancient times. The therapeutic properties of this product, which has rich biological content, are still being investigated with new approaches. In this study, the effect of RJ on telomere length, some antioxidant parameters, and lipid profile was examined. This study will contribute to the literature as it is the first to evaluate the effect of RJ on the length of telomeres in damaged liver tissues. In the study, the levels of serum triglyceride, total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), aspartate transaminase (AST), alanine transaminase (ALT), telomerase, 8'-hydroxy-2'-deoxyguanosine (8-OHdG), and paraoxonase-1 (PON1) were investigated with enzyme-linked immunosorbent assay method and telomere lengths were investigated by real-time quantitative polymerase chain reaction. The increased TC, LDL-C levels, and AST and ALT activities in the serum after carbon tetrachloride (CCl4) administration approached the control level after RJ administration. PON1 activity decreased in groups with CCl4. PON1 activity increased after RJ administration. The level of 8-OHdG, which increased groups with CCl4, decreased after RJ administration. According to the results of telomere length analysis in liver tissues, telomere lengths in damaged tissues were significantly shortened with CCl4 application and increased with RJ application. Based on the findings of the study, it was concluded that RJ may have therapeutic effects on telomere lengths and some biochemistry parameters.


Subject(s)
Carbon Tetrachloride , Liver Diseases , Rats , Animals , Bees , Rats, Wistar , Carbon Tetrachloride/adverse effects , Cholesterol, LDL , Liver Diseases/drug therapy , Antioxidants/pharmacology , Antioxidants/therapeutic use , Liver , Aspartate Aminotransferases
18.
Front Psychol ; 14: 1222863, 2023.
Article in English | MEDLINE | ID: mdl-37519381

ABSTRACT

Introduction: Telomeres are protective end caps of chromosomes which naturally shorten with each cell division and thus with age. Short telomeres have been associated with many age-related diseases. Meditation has come to the fore as a mind-body practice which could influence the telomere dynamics underlying these phenomena. We previously reported meditation to be associated with higher telomerase levels, mindfulness and quality of life. Here, reporting on the same study population, we describe associations between long-term meditation and telomere length (TL), expression of hTERT and hTR genes and methylation of the promoter region of hTERT gene. Methods: Thirty healthy meditators and matched non-meditators were recruited. TL was measured using quantitative PCR, gene expression was assessed using reverse transcriptase PCR, and methylation level was quantified by bisulfite-specific PCR followed by Sanger sequencing. Comparisons between meditators and controls were carried out using t-tests, while Pearson correlation was used to identify correlations, and regression was used to identify predictors. Results: Males comprised 63.4% of each group with an average age of 43 years. On average, they had meditated daily for 5.82 h (±3.45) for 6.8 years (±3.27). Meditators had longer relative TLs (p = 0.020), and TL decreased with age (p < 0.001) but was not associated with other socio-demographic variables. Regression analysis showed that age (p < 0.001) and duration of meditation (p = 0.003) significantly predicted TL. The meditators showed higher relative expression of hTERT (p = 0.020) and hTR (p = 0.029) genes while the methylation level of the promoter region of hTERT gene was significantly lower when compared to non-meditators (p < 0.001). Negative correlations were identified between the methylation level of the promoter region of hTERT gene and the expression of the hTERT gene (p = 0.001) and duration of meditation (p = 0.001). Conclusion: The findings suggest that meditation as a lifestyle practice has multi-level beneficial effects on telomere dynamics with potential to promote healthy aging.

19.
Front Psychol ; 14: 1158760, 2023.
Article in English | MEDLINE | ID: mdl-37342644

ABSTRACT

Objective: Exhaustion, stress, and burnout have all been found to be reduced using techniques like yoga and meditation. This study was carried out to check the effectiveness of Heartfulness practice (a form of meditation) on certain psychological and genetic variables. Methods: A total of 100 healthy individuals (aged 18-24) were recruited and randomized into two groups-Heartfulness intervention and control group. The intervention was carried out for 03 months. Participants from both groups were analysed for their cortisol levels and telomere length before and after the intervention. Psychometric measures of anxiety, perceived stress, well-being and mindfulness were carried out using Beck Anxiety Inventory (BAI), Perceived Stress Scale (PSS), WHO-Well-being Index (WHO-WBI) and Five Facet Mindfulness Questionnaire (FFMQ). Results: The cortisol levels in the meditators group significantly decreased (p < 0.001) after the intervention as compared to the non-meditators group, whereas, the telomere length increased in the mediators group. This increase was not significant (p > 0.05). Anxiety and perceived stress also decreased post intervention, and well-being as well as mindfulness increased, as assessed by the questionnaire tools, although the decrease in perceived stress was statistically insignificant (p > 0.05). A negative correlation was observed between telomere length and cortisol (stress biomarker), whereas a positive correlation was found between telomere length and well-being. Conclusion: Our data provide evidence that Heartfulness meditation practice can improve our mental health. Additionally, telomere length is shown to be affected by cortisol levels, and this meditation practice can also help to increase telomere length, and thereby slow down cellular aging. However, future studies with larger sample size are required to confirm our observations.

20.
Drug Metab Pers Ther ; 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-37254529

ABSTRACT

INTRODUCTION: Medicinal plants and herbs are the most important part of the Ayurveda. The term Rasayana in Charaka Samhita confers long life, youthfulness, strong body, freedom from diseases and the plants mentioned in Rsayana possess antiaging property. Aging is the collective term used for the complex detrimental physiological changes that reduce the functional ability of the cell. Oxidative stress, telomeres shortening, inflammation, and mitochondrial dysfunction are the main factors that regulate the aging process. Chronological aging is an irreversible process but the factors causing biological aging can be controlled. Ayurvedic herbs are better for the management of age-related problems. There are several natural bioactive agents present in plants that can delay the aging process in humans. They trigger actions like enhancing gene longevity and telomerase activity, ROS scavenging furthermore regeneration of tissues. CONTENT: The plants mentioned in the Rasayana of Ayurveda have antiaging potential and can be used to solve modern problems related to aging. Some Ayurvedic plants and their antiaging potential has explained in this review. The main causes of aging, medicinal plants and their use as potential antiaging mediator are covered in this study. SUMMARY: The process of aging is still an enigma. It is a complex, irretrievable, dynamic process that involves a number of factors and is subject to a number of environmental and genetic influences. Rasayana aspect has not been much investigated in clinical trials. Aging is considered to result from free radical damage. According to Charaka, Rasayana drugs open the partially or fully blocked channels. Many Rasayanas show free radical scavenging activity and has the potential to mitigate the effects of aging. It gives an overview of the significance of Ayurvedic medicinal plants as a source of inspiration and the use of these plants as remedies for antiaging. OUTLOOK: This study briefly outlooks the causes of aging and how medicinal plants can be used to reverse the aging process. In this study, we discussed the antiaging potential and mechanistic roles of Ayurvedic herbs. These herbs have the properties to slow down the natural process of aging and can successfully manage common age-related problems.

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