Taurine deficiency as a driver of aging.

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.

Integrity of hypothalamic-pituitary-testicular axis in exceptional longevity.

Hypothalamic integrity increasingly is being recognized as a marker of healthy longevity in rodent models. Insight into hypothalamic function in humans with exceptional longevity can be gained via investigation of the hypothalamic-pituitary-testicular (HPT) axis in men with exceptional longevity. This study aimed to characterize the HPT axis function, defined by levels of testosterone (T) and luteinizing hormone (LH), in 84 Ashkenazi Jewish men aged 90-106 years. We found that 94% of men exhibited preserved hypothalamic-pituitary function, as evidenced by either normal testosterone and LH levels (25%) or an appropriate rise in LH in response to aging-related primary testicular dysfunction (69%), a hormone pattern mirroring female menopause. Total T level was not associated with metabolic parameters or survival. These results demonstrate a high prevalence of testicular dysfunction with preserved hypothalamic-pituitary function in men with exceptional longevity. Thus, the role of hypothalamic integrity and HPT axis in healthy aging warrants further investigation.

Multi-Omics Interpretation of Anti-Aging Mechanisms for ω-3 Fatty Acids.

Aging is one of the hottest topics in biomedicine. Previous research suggested that ω-3 fatty acids have preventive effects on aging. However, most of previous studies on the anti-aging effects of ω-3 fatty acids are focused on clinical observations, and the anti-aging mechanisms of ω-3 fatty acids have not been fully elucidated. This stimulated our interest to use multi-omics data related to ω-3 fatty acids in order to interpret the anti-aging mechanisms of ω-3 fatty acids. First, we found that ω-3 fatty acids can affect methylation levels and expression levels of genes associated with age-related diseases or pathways in humans. Then, a Mendelian randomization analysis was conducted to determine whether there is a causal relationship between the effect of ω-3 fatty acids on blood lipid levels and variation in the gut microbiome. Our results indicate that the impact of ω-3 fatty acids on aging is partially mediated by the gut microbiome (including Actinobacteria, Bifidobacteria and Streptococcus). In conclusion, this study provides deeper insights into the anti-aging mechanisms of ω-3 fatty acids and supports the dietary supplementation of ω-3 fatty acids in aging prevention.

Impact of Selenium on Biomarkers and Clinical Aspects Related to Ageing. A Review.

Selenium (Se) is an essential dietary trace element that plays an important role in the prevention of inflammation, cardiovascular diseases, infections, and cancer. Selenoproteins contain selenocysteine in the active center and include, i.a., the enzymes thioredoxin reductases (TXNRD1-3), glutathione peroxidases (GPX1-4 and GPX6) and methionine sulfoxide reductase, involved in immune functions, metabolic homeostasis, and antioxidant defense. Ageing is an inevitable process, which, i.a., involves an imbalance between antioxidative defense and reactive oxygen species (ROS), changes in protein and mitochondrial renewal, telomere attrition, cellular senescence, epigenetic alterations, and stem cell exhaustion. These conditions are associated with mild to moderate inflammation, which always accompanies the process of ageing and age-related diseases. In older individuals, Se, by being a component in protective enzymes, operates by decreasing ROS-mediated inflammation, removing misfolded proteins, decreasing DNA damage, and promoting telomere length. Se-dependent GPX1-4 and TXNRD1-3 directly suppress oxidative stress. Selenoprotein H in the cell nucleus protects DNA, and selenoproteins residing in the endoplasmic reticulum (ER) assist in the removal of misfolded proteins and protection against ER stress. In this review, we highlight the role of adequate Se status for human ageing and prevention of age-related diseases, and further its proposed role in preservation of telomere length in middle-aged and elderly individuals.

Spectroscopic Signature of Red Blood Cells in a D-Galactose-Induced Accelerated Aging Model.

This work presents a semi-quantitative spectroscopic approach, including FTIR-ATR and Raman spectroscopies, for the biochemical analysis of red blood cells (RBCs) supported by the biochemical, morphological and rheological reference techniques. This multi-modal approach provided the description of the RBC alterations at the molecular level in a model of accelerated aging induced by administration of D-galactose (D-gal), in comparison to natural aging. Such an approach allowed to conclude that most age-related biochemical RBC membrane changes (a decrease in lipid unsaturation and the level of phospholipids, or an increase in acyl chain shortening) as well as alterations in the morphological parameters and RBC deformability are well reflected in the D-gal model of accelerated aging. Similarly, as in natural aging, a decrease in LDL level in blood plasma and no changes in the fraction of glucose, creatinine, total cholesterol, HDL, iron, or triglycerides were observed during the course of accelerated aging. Contrary to natural aging, the D-gal model led to an increase in cholesterol esters and the fraction of total esterified lipids in RBC membranes, and evoked significant changes in the secondary structure of the membrane proteins. Moreover, a significant decrease in the phosphorous level of blood plasma was specific for the D-gal model. On the other hand, natural aging induced stronger changes in the secondary structures of the proteins of the RBCs' interior. This work proves that research on the aging mechanism, especially in circulation-related diseases, should employ the D-gal model with caution. Nonetheless, the D-gal model enables to imitate age-related rheological alterations in RBCs, although they are partially derived from different changes observed in the RBC membrane at the molecular level.

1,25-Dihydroxyvitamin D deficiency accelerates male reproductive senescence in aging mice and 1,25(OH)2D3 alleviates oxidative stress via NF-κB/SOD.

1,25(OH)2D3 has been demonstrated to exert direct actions on male reproductive system in humans or in animals. With age, renal synthesis of 1,25(OH)2D3 declines significantly, and vitamin D supplementation has been found to alleviate the manifestations of male reproductive aging. Therefore, the relationship between 1,25(OH)2D3 and male reproductive aging needs further study. To determine whether 1,25(OH)2D3 deficiency accelerates male reproductive senescence in aging mice, wild-type and 1α(OH)ase-/- male mice fed a rescue diet after weaning, and the reproductive phenotypes were evaluated at 12-18 mo of age. We demonstrated that 1,25(OH)2D3 deficiency accelerated male reproductive senescence, representing lower fertility efficiency and gonadal hormone levels, reducing cell proliferation, and increasing cell apoptosis, cellular senescence, and the senescence-associated secretory phenotype (SASP). We confirmed that the increased oxidative stress and DNA damage detected in 1α(OH)ase-/- mice resulted in accelerated reproductive senescence in reproductive system, since exogenous antioxidant pyrroloquinoline quinone (PQQ) supplementation could largely rescue reproductive aging phenotype. We further validated the antioxidant effect of 1,25(OH)2D3 in aging wild-type mice and senescent Leydig cells by treated 18-mo-old wild-type male mice or TM3 cells with 1,25(OH)2D3 or vehicle. We assessed the differential gene expression between grouped senescent TM3 cells using RNA-Seq and verified 1,25(OH)2D3 exerted an antioxidant role by acting NF-κB/SOD. This study suggests that 1,25(OH)2D3 deficiency accelerates male reproductive senescence in aging mice by increasing oxidative stress and 1,25(OH)2D3 plays a role in alleviating oxidative stress via NF-κB/SOD signaling pathway.NEW & NOTEWORTHY Based on this studies, we propose that 1,25(OH)2D3 can delay male reproductive aging, and we also propose that 1,25(OH)2D3 regulates NF-κB to exert antioxidant effect. Therefore, by targeting a fundamental aging mechanism, 1,25(OH)2D3 may be an effective agent in maintaining fertility and postponing male reproductive senescence.

A 6-month, double-blind, placebo-controlled, randomized trial to evaluate the effect of Eurycoma longifolia (Tongkat Ali) and concurrent training on erectile function and testosterone levels in androgen deficiency of aging males (ADAM).

BACKGROUND: Androgen deficiency of aging males (ADAM) largely manifests as sexual symptoms. Erectile dysfunction is one of the most common symptoms of ADAM. AIM: To ascertain the effect of concurrent training and supplementation with Eurycoma longifolia on erectile function and testosterone levels in men with ADAM, and the association of erectile function with levels of total testosterone. METHODS: 6-month, randomized, double-blind, placebo-controlled four-arm clinical. 45 men (47.38 ± 5.03 years) were randomized into 4 groups (G1: control + placebo; G2: control + Eurycoma longifolia; G3: concurrent training + placebo; G4: concurrent training + Eurycoma longifolia). 22 received a 200 mg supplement of Eurycoma longifolia and 23 underwent the intervention with concurrent training, 3 times a week for 60 min at progressive intensity. OUTCOMES: International Index of Erectile Function (IIEF-5), Aging Male Scale (AMS) and total testosterone. RESULTS: Erectile function demonstrated improvements in both interventions; however, the most significant results were obtained by men allocated to concurrent training + Eurycoma longifolia. CLINICAL IMPLICATIONS: A 200 mg supplement of Eurycoma longifolia and the practice of concurrent training for 6 months significantly improved the erectile function of men with ADAM. STRENGTHS & LIMITATIONS: The study's design stands out as a strength, in addition to the six-month intervention. The main limitation is the study not having groups that used only Eurycoma longifolia and only concurrent training. CONCLUSION: The combination of Eurycoma longifolia and concurrent training improved erectile function and increased total testosterone levels in men with ADAM.

Taurine supplementation reduces myeloperoxidase and matrix-metalloproteinase-9 levels and improves the effects of exercise in cognition and physical fitness in older women.

Immunosenescence contributes to cognitive impairment and neurodegeneration, and those conditions could be attenuated by non-pharmacological anti-inflammatory strategies, such as exercise and supplementation with the amino acid taurine. Since taurine body content decreases with aging, we investigated the effects of supplementation (alone and combined with exercise) on oxidative stress, extracellular matrix degradation, white blood cells, neurotrophins, cognition and physical fitness of elderly women. Forty-eight women (83.58 ± 6.98 years) were enrolled into exercise training only (EO: n = 13), taurine supplementation (TS: n = 12), exercise training + taurine supplementation (ETTS: n = 11), and control group (CG: n = 12). All interventions lasted 14 weeks. Exercise was applied twice a week, and taurine was given once a day (1.5 g). Data collection occurred before and after interventions with the determination of myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) levels, and white blood cell counts (WBC). Montreal cognitive assessment (MoCA) and physical fitness tests were also evaluated. Concentration of MPO and MMP-9 decreased after intervention in TS (p < 0.05). No effect of time or time × group was observed for WBC parameters; however, univariate analysis showed a significant decrease in lymphocytes for TS, while an increase in monocytes occurred in the CG (p < 0.05). MoCA scores decreased over time in the CG (p < 0.05). Improvements in physical fitness occurred in ETTS (better agility and aerobic capacity), mostly likely due to exercise and boosted by taurine supplementation. No changes in BDNF levels were observed (p > 0.05), while NGF concentration were undetectable in almost subjects. Exercise together with taurine supplementation appears to be a valuable strategy to enhance health-related outcomes in older persons.

The Relationship Between Vitamin D and Telomere/Telomerase: A Comprehensive Review.

Telomeres are repetitive nucleotide sequences that together with the associated sheltrin complex protect the ends of chromosomes and maintain genomic stability. Evidences from various organisms suggests that several factors influence telomere length regulation, such as telomere binding proteins, telomere capping proteins, telomerase, and DNA replication enzymes. Recent studies suggest that micronutrients, such as vitamin D, folate and vitamin B12, are involved in telomere biology and cellular aging. In particular, vitamin D is important for a range of vital cellular processes including cellular differentiation, proliferation and apoptosis. As a result of the multiple functions of vitamin D it has been speculated that vitamin D might play a role in telomere biology and genomic stability. In this study, our main goal is investigating the relationship between telomerase enzyme and vitamin D. Findings of this study suggest that higher vitamin D concentrations, which are easily modifiable through nutritional supplementation, are associated with longer LTL, which underscores the potentially beneficial effects of this hormone on aging and age-related diseases. Vitamin D may reduce telomere shortening through anti-inflammatory and anti-cell proliferation mechanisms. Significant Low levels of telomerase activity create short telomeres, which in turn signal exit from the cell cycle resulting in cell senescence and apoptosis. In follow-up examination, the patients who remained vitamin D deficient tended to have shorter telomeres than those patients whose 25-hydroxyvitamin D levels were depleted. Increasing 25-hydroxyvitamin D levels in patients with SLE may be beneficial in maintaining telomere length and preventing cellular aging. Moreover, anti-telomere antibody levels may be a promising biomarker of SLE status and disease activity.

Association Between Erythrocyte Levels of n-3 Polyunsaturated Fatty Acids and Risk of Frailty in Community-Dwelling Older Adults: The Korean Frailty and Aging Cohort Study.

BACKGROUND: Inflammation is a major risk factor for frailty, but n-3 polyunsaturated fatty acids (PUFA) has been suggested as an anti-inflammatory agent. The present study aimed to investigate the hypothesis that the higher erythrocyte levels of long-chain n-3 PUFA were associated with lower odds of frailty and frailty criterion. METHODS: Cross-sectional analysis from the Korean Frailty and Aging Cohort Study, a total of 1,435 people aged 70-84 years were included. Sex- and age-stratified community residents, drawn in urban and rural regions nationwide, were eligible for participation in the study. All participants were categorized as frail and nonfrail according to the Cardiovascular Health Study index. RESULTS: The likelihood of frailty was inversely associated with the erythrocyte levels of eicosapentaenoic acid (EPA; odds ratio [OR] per unit 0.33; 95% confidence interval [CI] 0.14-0.77; p for trend = .002) and docosahexaenoic acid (DHA; OR per unit 0.42; 95% CI 0.20-0.87; p for trend = .018). Among each frailty criterion, the likelihood of slow walking speed was associated with erythrocyte levels of EPA and DHA, and the likelihood of exhaustion was inversely associated with the erythrocyte levels of DHA. CONCLUSIONS: The present study showed that the frailty and frailty criterion were significantly associated with lower erythrocyte levels of long-chain n-3 PUFA, suggesting that lower n-3 PUFA could be a marker for the risk of frailty.

Horticultural Therapy Reduces Biomarkers of Immunosenescence and Inflammaging in Community-Dwelling Older Adults: A Feasibility Pilot Randomized Controlled Trial.

BACKGROUND: With the challenges that aging populations pose to health care, interventions that facilitate alleviation of age-related morbidities are imperative. A prominent risk factor for developing age-related morbidities is immunosenescence, characterized by increased chronic low-grade inflammation, resulting in T-cell exhaustion and senescence. Contact with nature and associated physical activities have been shown to boost immunity in older adults and may be promoted in the form of horticultural therapy (HT). We aimed to examine the effects of HT on immunosenescence. METHOD: We conducted a randomized controlled trial with 59 older adults assigned to either the HT intervention or waitlist control group. Older adults in the HT intervention group underwent HT intervention program over 6 months. Venous blood was drawn at baseline and at the third and sixth month from the commencement of this study. For participants who attended all 3 blood collection time points (HT: n = 22; waitlist: n = 24), flow cytometry analysis was performed on whole blood samples to evaluate the kinetics of lymphocyte subsets over the intervention period, revealing the composition of CD4+ and CD8+ subsets expressing exhaustion markers-CD57, CTLA4, and KLRG1. Enzyme-linked immunosorbent assays were employed to measure changes in plasma IL-6 levels. RESULTS: HT is associated with increased numbers of naive CD8+ T cells and fewer CTLA4-expressing terminally differentiated effector CD4+ and CD8+ memory T cells re-expressing CD45RA (TEMRA). Furthermore, IL-6 levels were reduced during HT, and the frequencies of naive and TEMRA CD8+ T cells were found to be associated with IL-6 levels. CONCLUSION: HT is associated with a reduction in the levels of biomarkers that measure the extent of T-cell exhaustion and inflammaging in older adults. The positive effects of HT on T-cell exhaustion were associated with the reduction of IL-6 levels.

Nutritional Biomarkers and Associated Factors in Community-Dwelling Older Adults: Findings from the SHIELD Study.

Aging is associated with intrinsic and extrinsic changes which affect the nutrient intake and nutritional status of an older individual. Suboptimal nutritional status is linked with adverse health outcomes. There are limited data in this area for community-dwelling older adults who are not at risk of malnutrition. The objective of this study was to describe the nutritional biomarkers in 400 community-dwelling older adults (aged ≥65 years) with normal nutritional status (Malnutrition Universal Screening Test score of 0) in Singapore and to identify factors associated with these biomarkers. The majority of the participants had normal levels of pre-albumin, albumin, total protein, creatinine, zinc, corrected calcium, vitamin B12, ferritin and hemoglobin. Females had significantly higher levels of corrected calcium and vitamin B12 than males, whereas males had significantly higher levels of pre-albumin, albumin, creatinine, serum ferritin, 25-hydroxyvitamin D (25(OH)D) and hemoglobin than females. About half of the participants (52%) had low level of 25(OH)D (<30 µg/L) and 10% had low zinc level (<724 µg/L). Among those with low level of 25(OH)D, 74% had 25(OH)D insufficiency (20-<30 µg/L) and 26% had 25(OH)D deficiency (<20 µg/L). Younger age, female gender, non-Chinese ethnicity and no intake of vitamin D supplement were associated with lower serum 25(OH)D level, whereas higher body mass index (BMI) was associated with low zinc level. These findings highlight the problem of hidden nutritional insufficiencies can be missed in seemingly normal nourished community-dwelling older adults.

Melatonin down-regulates steroidal hormones, thymocyte apoptosis and inflammatory cytokines in middle-aged T. cruzi infected rats.

Chagas disease, triggered by the flagellate protozoan Trypanosoma cruzi (T. cruzi) plays a potentially threat to historically non-endemic areas. Considerable evidence established that the immuno-endocrine balance could deeply influence the experimental T. cruzi progression inside the host's body. A high-resolution multiple reaction monitoring approach (MRMHR) was used to study the influence of melatonin on adrenal and plasma steroidal hormones profile of T. cruzi infected Wistar rats. Young (5 weeks) and middle-aged (18 months) male Wistar rats received melatonin (5 mg/Kg, orally) during the acute Chagas disease. Corticosterone, 11-dehydrocorticosterone (11-DHC), cortisol, cortisone, aldosterone, progesterone and melatonin concentration were evaluated. Interleukin-1 alpha and ß (IL-1α and ß), IL-6 and transforming growth factor beta (TGF-ß) were also analyzed. Our results revealed an increased production of corticosterone, cortisone, cortisol and aldosterone in middle-aged control animals, thus confirming the aging effects on the steroidal hormone profile. Serum melatonin levels were reduced with age and predominantly higher in young and middle-aged infected rats. Melatonin treatment reduced the corticosterone, 11-DHC, cortisol, cortisone, aldosterone and progesterone in response to T. cruzi infection. Decreased IL-1 α and ß concentrations were also found in melatonin treated middle-aged infected animals. Melatonin treated middle-aged control rats displayed reduced concentrations of TGF-ß. Melatonin levels were significantly higher in all middle-aged rats treated animals. Reduced percentages of early and late thymocyte apoptosis was found for young and middle-aged melatonin supplemented rats. Finally, our results show a link between the therapeutic and biological effects of melatonin controlling steroidal hormones pathways as well as inflammatory mediators.

Trimethylamine-N-Oxide Promotes Age-Related Vascular Oxidative Stress and Endothelial Dysfunction in Mice and Healthy Humans.

Age-related vascular endothelial dysfunction is a major antecedent to cardiovascular diseases. We investigated whether increased circulating levels of the gut microbiome-generated metabolite trimethylamine-N-oxide induces endothelial dysfunction with aging. In healthy humans, plasma trimethylamine-N-oxide was higher in middle-aged/older (64±7 years) versus young (22±2 years) adults (6.5±0.7 versus 1.6±0.2 µmol/L) and inversely related to brachial artery flow-mediated dilation (r2=0.29, P<0.00001). In young mice, 6 months of dietary supplementation with trimethylamine-N-oxide induced an aging-like impairment in carotid artery endothelium-dependent dilation to acetylcholine versus control feeding (peak dilation: 79±3% versus 95±3%, P<0.01). This impairment was accompanied by increased vascular nitrotyrosine, a marker of oxidative stress, and reversed by the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl. Trimethylamine-N-oxide supplementation also reduced activation of endothelial nitric oxide synthase and impaired nitric oxide-mediated dilation, as assessed with the nitric oxide synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester). Acute incubation of carotid arteries with trimethylamine-N-oxide recapitulated these events. Next, treatment with 3,3-dimethyl-1-butanol for 8 to 10 weeks to suppress trimethylamine-N-oxide selectively improved endothelium-dependent dilation in old mice to young levels (peak: 90±2%) by normalizing vascular superoxide production, restoring nitric oxide-mediated dilation, and ameliorating superoxide-related suppression of endothelium-dependent dilation. Lastly, among healthy middle-aged/older adults, higher plasma trimethylamine-N-oxide was associated with greater nitrotyrosine abundance in biopsied endothelial cells, and infusion of the antioxidant ascorbic acid restored flow-mediated dilation to young levels, indicating tonic oxidative stress-related suppression of endothelial function with higher circulating trimethylamine-N-oxide. Using multiple experimental approaches in mice and humans, we demonstrate a clear role of trimethylamine-N-oxide in promoting age-related endothelial dysfunction via oxidative stress, which may have implications for prevention of cardiovascular diseases.

Effects of Forest Therapy on Health Promotion among Middle-Aged Women: Focusing on Physiological Indicators.

Women experience more stress in middle age than in other life stages, and health in middle age is vital, because it influences the quality of life in old age. In this study, the effects of a forest therapy program on physiological changes in 53 middle-aged women (divided into two groups) who lived in the city were examined. One group participated in a three-day program in the forest, followed by three days in the city; the other group participated in a three-day program in the city, followed by three days in the forest. Forest experiments were conducted in a "healing forest," and urban experiments were conducted near a university campus. Blood tests were performed to evaluate the physiological effects of forest therapy. Differences in serotonin levels and vitamin D levels were verified before and after the forest (experimental group) and urban (control group) programs through paired t-tests. Statistically significant increases in serotonin levels were noted for participants in the forest program; vitamin D levels also increased, but not by statistically significant values. The findings of this study verify that forest therapy programs promote health among middle-aged women, and may prevent disease and improve quality of life.

Short communication: Variation in serum immunoglobulin G concentrations from birth to 112 days of age in Holstein calves fed a commercial colostrum replacer or maternal colostrum.

Serum IgG concentrations in dairy calves change throughout their first weeks of life, peaking at 24 h and then steadily decreasing until calves begin to produce endogenous IgG. The objective of this study was to observe serum IgG dynamics from birth until 16 wk of life in calves fed either maternal colostrum (MC) or colostrum replacer (CR). A total of 44 Holstein calves were randomly assigned to 1 of the 4 colostrum treatments and followed throughout the study. Treatments consisted of feeding high-quality MC, low-quality MC supplemented with CR, or 1 of 2 distinct levels of IgG concentration from CR. Overall, the interaction between type of colostrum fed and sampling time was significant. Individual differences for this effect were found at d 1, 7, 14, 21, 28, and 98, while the other time points were not different.

Effect of 9 - PAHSA on cognitive dysfunction in diabetic mice and its possible mechanism.

Diabetes mellitus (DM) is currently a major global health problem, which is associated with the development of cognitive dysfunction. However, although numerous clinical drugs for hyperglycemia have been used at present, safer and more effective therapeutic intervention strategies for diabetic cognitive impairments are still a huge challenge. Recently, several studies have indicated that a novel class of branched palmitic acid esters of hydroxyl stearic acids (PAHSAs) may have anti-diabetes and anti-inflammatory effects in insulin-resistant mice. Herein, whether the 9-PAHSA that one of the PAHSAs can attenuates DM-associated cognitive impairment in a mouse model of type 2 diabetes has been investigated. Our results showed that 9-PAHSA mildly prevented deficits of spatial working memory in Y-maze test while reversed the preference bias toward novel mice in Social choice test. Furthermore, the effect of REST on cognitive impairment of diabetes was explored for the first time. It was found that the expression of REST in diabetic mice increased, and the expression of target protein BDNF (Brain-derived neurotrophic factor) was decreased. After administration of 9-PAHSA, the situation was reversed. In summary, we conclude that exogenous supplement of 9-PAHSA can improve DM-related cognitive impairment to some extent, and the protective effect may be associated with decreased REST/NRSF (repressor element-1 silencing transcription factor/neuron-restrictive silence factor) and upregulated BDNF expression in frontal cortex.

Homocysteine: Its Possible Emerging Role in At-Risk Population Groups.

Increased plasma homocysteine is a risk factor for several pathological disorders. The present review focused on the role of homocysteine (Hcy) in different population groups, especially in risk conditions (pregnancy, infancy, old age), and on its relevance as a marker or etiological factor of the diseases in these age groups, focusing on the nutritional treatment of elevated Hcy levels. In pregnancy, Hcy levels were investigated in relation to the increased risk of adverse pregnancy outcomes such as small size for gestational age at birth, preeclampsia, recurrent abortions, low birth weight, or intrauterine growth restriction. In pediatric populations, Hcy levels are important not only for cardiovascular disease, obesity, and renal disease, but the most interesting evidence concerns study of elevated levels of Hcy in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Finally, a focus on the principal pathologies of the elderly (cardiovascular and neurodegenerative disease, osteoporosis and physical function) is presented. The metabolism of Hcy is influenced by B vitamins, and Hcy-lowering vitamin treatments have been proposed. However, clinical trials have not reached a consensus about the effectiveness of vitamin supplementation on the reduction of Hcy levels and improvement of pathological condition, especially in elderly patients with overt pathologies, suggesting that other dietary and non-dietary factors are involved in high Hcy levels. The importance of novel experimental designs focusing on intra-individual variability as a complement to the typical case-control experimental designs and the study of interactions between different factors it should be emphasized.

Vitamin K as a Diet Supplement with Impact in Human Health: Current Evidence in Age-Related Diseases.

Vitamin K health benefits have been recently widely shown to extend beyond blood homeostasis and implicated in chronic low-grade inflammatory diseases such as cardiovascular disease, osteoarthritis, dementia, cognitive impairment, mobility disability, and frailty. Novel and more efficient nutritional and therapeutic options are urgently needed to lower the burden and the associated health care costs of these age-related diseases. Naturally occurring vitamin K comprise the phylloquinone (vitamin K1), and a series of menaquinones broadly designated as vitamin K2 that differ in source, absorption rates, tissue distribution, bioavailability, and target activity. Although vitamin K1 and K2 sources are mainly dietary, consumer preference for diet supplements is growing, especially when derived from marine resources. The aim of this review is to update the reader regarding the specific contribution and effect of each K1 and K2 vitamers in human health, identify potential methods for its sustainable and cost-efficient production, and novel natural sources of vitamin K and formulations to improve absorption and bioavailability. This new information will contribute to foster the use of vitamin K as a health-promoting supplement, which meets the increasing consumer demand. Simultaneously, relevant information on the clinical context and direct health consequences of vitamin K deficiency focusing in aging and age-related diseases will be discussed.

Vitamin D Status Across Age Groups in Turkey: Results of 108,742 Samples from a Single Laboratory

Objective: The aim was to determine vitamin D status in the general population in Turkey between 2011 and 2016, and to evaluate the effectiveness of the national vitamin D supplementation programme. Methods: Serum 25-hydroxyvitamin D (25-OHD) measurement data were retrieved from an internationally accredited laboratory, operating nationwide. A total of 108,742 measurements of 25-OHD were analyzed using the cut-off values of 0-11 ng/mL, 12-19 ng/mL, 20-49 ng/mL, 50-70 ng/mL and >70 ng/mL for vitamin D deficiency, insufficiency, sufficiency, possibly harmful and excess respectively. Results: The mean±standard deviation 25-OHD level was 21.6±13.3 ng/mL. Mean 25-OHD concentrations by age groups were: 37.3 ng/mL, 30.1 ng/mL and 23.7 ng/mL for <1, 1-10 and 11-18 year old groups, respectively. Mean 25-OHD levels of children <1 year and 1-3 years of age were significantly higher than those found in other age groups. The prevalence of vitamin D deficiency (<12 ng/mL) was lowest in children at 1-3 years of age (5%). In subjects older than 18 years of age, mean 25-OHD levels were 18.2 ng/mL, 20.1 ng/mL, 21.9 ng/mL and 21.1 ng/mL for age groups 19-30, 31-50, 51-70 and >70 years, respectively. Conclusion: Successful implementation of the national vitamin D supplementation programme, appears to have nearly eliminated vitamin D deficiency for children under 1-years of age. However, the positive impact of the vitamin D supplementation diminishes as children get older suggesting that supplementation may be required in the older children and adults. In addition, improved awareness of the benefits and risks of excess vitamin D should prevent unnecessary and excessive use of vitamin D supplements.