“Daphnane diterpenes with a 5/7/6-tricyclic ring system exhibit potent anti-HIV activity but are found in low abundance as plant natural products. In this study, an effective approach based on mass spectrometric fragmentation pathways was conducted to specifically recognize and isolate anti-HIV compounds of this type from Daphne genkwa.”
“Chili pepper is a common ingredient in Italians kitchens, and over the centuries, it has been praised for its supposed therapeutic virtues. Now, an Italian study shows that people who consume it on a regular basis have an all-cause mortality risk 23 percent lower than those who do not consume it.”
https://medicalxpress.com/news/2019-12-consumption-chili-pepper-death-heart.html
EnGeneIC Limited, a clinical-stage biopharmaceutical company advancing its proprietary EDVâ„¢ nanocell platform for targeted cyto-immunotherapy in cancer, announced that it is the winner in this year’s Drug Delivery Technology category given by Fierce Innovation Awards – LifeSciences Edition, which is a peer-reviewed awards program from the publisher of FierceBiotech and FiercePharma.
EnGeneIC’s EDVâ„¢ is a globally unique cyto-immunotherapy that is able to directly kill cancer cells as well as provoking a potent anti-tumor immune response with little to no toxicity, even in late stage drug-resistant cancers.
Highlights
• SWS suppression during nighttime sleep leads to a significant increase in salivary melatonin.
• Elevated melatonin appears to play a key role in glucose tolerance changes after disturbed sleep.
• Melatonin’s effect on morning glucose tolerance depends on its secretion timing.
• Durations of REM sleep and nocturnal awakenings appear to play an important role in melatonin secretion and glucose tolerance.
• Glucose tolerance is associated with the total duration of undisturbed sleep and the length of REM sleep rather than the amount of SWS.
https://www.sciencedirect.com/science/article/abs/pii/S1389945719316405
Mitochondria are iconic structures in biochemistry and cell biology, traditionally referred to as the powerhouse of the cell due to a central role in energy production. However, modern-day mitochondria are recognized as key players in eukaryotic cell biology and are known to regulate crucial cellular processes, including calcium signalling, cell metabolism and cell death, to name a few. In this review, we will discuss foundational knowledge in mitochondrial biology and provide snapshots of recent advances that showcase how mitochondrial function regulates other cellular responses.
Background: Vernonia anthelmintica (L.) willd is a traditional urgur herb in China for a long history. Its alcohol extract (AVE) has been proved to promote hair follicle growth in C57BL/6 mice. We conducted this study to investigate the hair-growth effects of AVE in stressed mice and its possible mechanism of action
Results: Our results showed that AVE counteract murine hair follicle growth inhibition caused by chronic restraint stress via inducing the conversion of telogen to anagen and inhibiting catagen premature, increasing bulb keratinocytes and bulge stem cells proliferation, promoting melanogenesis, and reducing the numbers of substance P and calcitonin gene-related peptide nerve fibers. Furthermore, AVE also counteracted murine hair follicle growth inhibition caused by substance P in organ culture. Conclusion: These results suggest that AVE counteract stress-induced hair follicle growth inhibition in C57BL/6 mice in vivo and in vitro, and may be an effective new candidate for treatment of stress-induced hair loss.
https://bmccomplementalternmed.biomedcentral.com/track/pdf/10.1186/s12906-019-2744-9
Highlights
•Potassium (K+) channels are key regulators of cell excitability in several tissues.
•A dysregulation of K+ channels is associated with Alzheimer’s disease (AD).
•The role of K+ channels in AD is not completely elucidated.
•Understanding their functions will be helpful for clarifying AD pathogenesis.
•Modulating K+ channel expression should be useful for developing novel drugs.
Potassium channels in the neuronal homeostasis and neurodegenerative pathways underlying Alzheimer’s Disease: an update – ScienceDirect
“Mitochondria, tiny structures present in most cells, are known for their energy-generating machinery. Now, researchers have discovered a new function of mitochondria: they set off molecular alarms when cells are exposed to stress or chemicals that can damage DNA, such as chemotherapy.”
“In this report, we demonstrate that the rapamycinâ€dependent improvement of diastolic function is highly persistent, while decreases in both cardiac hypertrophy and passive stiffness are substantially persistent 8 weeks after cessation of an 8â€week treatment of rapamycin in both male and female 22†to 24â€monthâ€old C57BL/6NIA mice.”
“These data indicate that dairy consumption leads to systemic effects, which may promote mitochondrial biogenesis in key target tissues such as muscle and adipose tissue both by direct activation of SIRT1 as well as by SIRT1-independent pathways.”
Notice the word dairy is used, not milk. see our previous post on milkand its mTor activation and AMPK suppression.
“Mitochondria are fascinating structures of the cellular compartments that generate energy to run the cells. However, inherent disorders of mitochondria due to diabetes can cause major disruption of metabolism that produces huge amount of reactive oxygen species (ROS). Here we study the elevated level of ROS provoked by high glucose (HG) environment triggered mitochondrial dysfunction, inflammatory response and apoptosis via stress signalling pathway in keratinocytes. Our results demonstrated that elevated glucose level in keratinoctes, increase the accumulations of ROS and decrease in cellular antioxidant capacities.”
High glucose augments ROS generation regulates mitochondrial dysfunction and apoptosis via stress signalling cascades in keratinocytes. – PubMed – NCBI
“Highlights
•The first study to assess the role of oral zinc supplementation in pediatric β-TM patients with DM.
•Zinc decreased hemolysis and iron burden.
•Zinc decreased FBG and HOMA-IR while increased fasting C peptide.
•Oral zinc improved glycemic control and decreased urinary albumin excretion.
•No adverse reactions were observed due to zinc supplementation.”
Zinc supplementation improves glucose homeostasis in patients with β-thalassemia major complicated with diabetes mellitus: A randomized controlled trial – ScienceDirect
“Objective. The purpose of present study was to investigate the potential mechanism underlying the protective effect of Shenling Baizhu San (SLBZS) on nonalcoholic fatty liver disease (NAFLD) by microRNA (miRNA) sequencing. Methods. Thirty male Wistar rats were randomly divided into a normal control (NC) group, a high-fat diet (HFD) group, and an SLBZS group. After 12 weeks, the biochemical parameters and liver histologies of the rats were assessed. The Illumina HiSeq 2500 sequencing platform was used to analyse the hepatic miRNA expression profiles. Representative differentially expressed miRNAs were further validated by qRT-PCR. The functions of the differentially expressed miRNAs were analysed by bioinformatics. Results. Our results identified 102 miRNAs that were differentially expressed in the HFD group compared with the NC group. Among those differentially expressed miRNAs, the expression levels of 28 miRNAs were reversed by SLBZS administration, suggesting the modulation effect of SLBZS on hepatic miRNA expression profiles. The qRT-PCR results confirmed that the expression levels of miR-155-5p, miR-146b-5p, miR-132-3p, and miR-34a-5p were consistent with those detected by sequencing. Bioinformatics analyses indicated that the target genes of the differentially expressed miRNAs reversed by SLBZS were mainly related to metabolic pathways. Conclusion. This study provides novel insights into the mechanism of SLBZS in protecting against NAFLD; this mechanism may be partly related to the modulation of hepatic miRNA expression and their target pathways.”
Chinese Herbal Medicine Formula Shenling Baizhu San Ameliorates High-Fat Diet-Induced NAFLD in Rats by Modulating Hepatic MicroRNA Expression Profiles
Have you considered getting your DNA sequenced? Wonder what kind of information you could expect out of it?
I recently got my DNA sequenced at Self Decode and the results are in! Let’s take a look at whats in there and how I might be able to use it to improve my health and lifespan.
Now, what does this mean and what can I do about it?
Along with the report are sources to NIH publications to back the assertions. You also get deeper reports on each of those subject areas including MTFHR, APOE, Mood, Cognitive, Essential Minerals, Vitamins, Sleep, Cardiovascular, Inflammation and Fitness. You also get a personalised blog that shows you articles related to SNPs in your results.
I’m not saying that this is the best DNA service but it’s the one I chose and this is what I got. It seems quite comprehensive and does a good job at explaining what it all means and how I can adjust my diet and lifestyle to account for deficiencies caused by gene mutations. If this is something you are interested in then it might be an option for you.
“Observed changes show the potential of intense physical exercise to reduce levels of systemic basal inflammation as well as the potential for IgG N-glycosylation to serve as a sensitive longitudinal systemic inflammation marker.”
https://www.frontiersin.org/articles/10.3389/fphys.2019.01522/abstract
“Wish you could still be YOU…only younger? Learn how science is turning back time”
What a great project and initiative from a group of school girls. Looking at indoor plants to help with mental health.
For those who plan to take high-dose niacin, the best advice appears to be to start a very low dose, e.g. 25 mg/d. This may cause a skin flush (30-60 minutes of warm skin) at first, but over several days the body gradually adapts to this dose and does not cause the skin flush. Then, slowly increase the dose over several weeks, taking the niacin in divided doses throughout the day, building up to 500 mg/d and over several months up to 1000 mg/d or higher, in consultation with your physician. You can start by breaking up 100 mg tablets into 4 pieces, taking one 25 mg piece per day at first, then after a few days increasing to 2 per day, and later up to 4 of the 25 mg pieces per day, one before each snack or meal. Once the body adapts to this dose, you may increase to one or more 100 mg tablets per day, and so on. [7] If at very high doses (1000 mg/day or higher) you note changes in your vision, especially in the central region (the fovea and macula) that you use to read fine print, you may want to lower the daily niacin dose by 50% or more to 1000 mg/day or below in divided doses. The vision problems may then disappear after a few weeks. This threshold effect has been reported by ophthalmologists who have studied the condition. [6] Of course, with any regimen of high-dose niacin, you should consult and work with your own physician.
Understanding Niacin Side Effects
Orthomolecular Medicine News Service
OMNS archive link http://orthomolecular.org/resources/omns/index.shtml
“PP2A inhibition by LB100 significantly ameliorates hepatic steatosis by regulating hepatic lipogenesis and fatty acid oxidation via the AMPK/Sirt1 pathway. LB100 may be a potential therapeutic agent for NAFLD.”
“Autism spectrum disorder (ASD) has a strong and complex genetic component with an estimate of more than 1000 genes implicated cataloged in SFARI (Simon0 s Foundation Autism Research Initiative) gene database. A significant part of both syndromic and idiopathic autism cases can be attributed to disorders caused by the mechanistic target of rapamycin (mTOR)-dependent translation deregulation. We conducted gene-set analyses and revealed that 606 out of 1053 genes (58%) included in the SFARI Gene database and 179 out of 281 genes (64%) included in the first three categories of the database (“high confidenceâ€, “strong candidateâ€, and “suggestive evidenceâ€) could be attributed to one of the four groups: 1. FMRP (fragile X mental retardation protein) target genes, 2. mTOR signaling network genes, 3. mTOR-modulated genes, 4. vitamin D3 sensitive genes. The additional gene network analysis revealed 43 new genes and 127 new interactions, so in the whole 222 out of 281 (79%) high scored genes from SFARI Gene database were connected with mTOR signaling activity and/or dependent on vitamin D3 availability directly or indirectly. We hypothesized that genetic and/or environment mTOR hyperactivation, including provocation by vitamin D deficiency, might be a common mechanism controlling the expressivity of most autism predisposition genes and even core symptoms of autism.”
“the use of AmO (Amaranth Oil) instead of RaO may promote a proatherogenic lipid profile in obese and overweight inhabitants. “
Monika Dusâ€Zuchowska 1, Jaroslaw Walkowiak 1,*, Anna Morawska 2, Patrycja Krzyzanowska†Jankowska 1, Anna Miskiewiczâ€Chotnicka 1, Juliusz Przyslawski 2 and Aleksandra Lisowska 1 1 Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, 60â€572 Poznan, Poland; monzuchowska@gmail.com (M.D.â€Z.); p.krzyzanowska81@gmail.com (P.K.â€J.); chotnicka@ump.edu.pl (A.M.â€C.); alisowska@ump.edu.pl (A.L.) 2 Department of Bromatology, Poznan University of Medical Sciences, 60â€354 Poznan, Poland; akm@ump.edu.pl (A.M.); jprzysla@ump.edu.pl (J.P.) * Correspondence: jarwalk@ump.edu.pl; Tel.: +48â€61849â€1432 Received: 13 November 2019; Accepted: 13 December 2019; Published: 16 December 2019
” We reviewed and discussed underlying mechanisms of CR from an aspect of CR genes. It should be stressed that the isoform specificity of FoxO transcription factors for longevity becomes apparent under CR conditions but not AL conditions. Npy and FoxO1 both play pleiotropic roles in aging and related disorders, depending on the nutritional state. As briefly described in Section 1 and Section 2, the life-extending effects of CR and reduced IGF-1 signaling are also sexually dimorphic. Genes associated with regulation of the aging process should be investigated carefully in a context-dependent manner, i.e., abilities of physiological adaptation for individuals against environmental challenges, particularly food shortage. “
• New masculinity ideologies question popular beliefs like “real men eat meatâ€.
• The more men identify with new masculinity, the less they eat meat.
• This is mediated by men’s meat attachment, which is weaker for new masculine men.
• New masculinity also correlates positively with attitudes towards vegetarians.
• Studies about meat and vegetarianism should consider within-gender differences.
“High protein intake, partly mediated by energy intake, may delay incident frailty in very old adults. Frailty prevention strategies in this age group should consider adequate provision of protein and energy.”
“WE WILL GIVE EVERY CHILD THE BEST POSSIBLE START IN LIFE BY ENSURING THEY GET THE BEST POSSIBLE MEDICAL CARE AS SOON AS THEY ENTER THE WORLD.”
UK Plans to Give All Children Full Genome Sequence at Birth
“Ageing is closely associated with and influenced by energy metabolism, and C/EBPβ is emerging as a key regulator of energy metabolism and longevity.”
https://www.cell.com/trends/genetics/fulltext/S0168-9525(19)30245-8?dgcid=raven_jbs_aip_email
“Hyposialylated IgG and FcγRIIB in endothelium are critically involved in obesity-induced hypertension in mice, and supportive evidence was obtained in humans. Interventions targeting these mechanisms, such as ManNAc supplementation, may provide novel means to break the link between obesity and hypertension.“
Chronic low-grade inflammation, particularly in adipose tissue, is an important modulator of obesity-induced insulin resistance. The Toll-like receptor 4 (Tlr4) is a key initiator of inflammatory responses in macrophages. We performed bone marrow transplantation (BMT) of Tlr4lps-del or control C57Bl/10J donor cells into irradiated wild-type C57Bl6 recipient mice to generate hematopoietic cell-specific Tlr4 deletion mutant (BMT-Tlr4−/−) and control (BMT-WT) mice. After 16 weeks of a high-fat diet (HFD), BMT-WT mice developed obesity, hyperinsulinemia, glucose intolerance, and insulin resistance. In contrast, BMT-Tlr4−/− mice became obese but did not develop fasting hyperinsulinemia and had improved hepatic and adipose insulin sensitivity during euglycemic clamp studies, compared to HFD BMT-WT controls. HFD BMT-Tlr4−/− mice also showed markedly reduced adipose tissue inflammatory markers and macrophage content. In summary, our results indicate that Tlr4 signaling in hematopoietic-derived cells is important for the development of hepatic and adipose tissue insulin resistance in obese mice.
Scientists like Prof Sinclair have evidence of speeding up, slowing, and even reversing aging.
“The amount of time we live is called lifespan. The length of time that a person is healthy and functional—not just alive—is called healthspan. Scientific understanding in these areas is advancing rapidly. Below are 12 things the collective thinks will help on your journey to a longer healthier you.Â
1. BOOST NAD+ LEVELS
2. POWER UP WITH ATP
3. CREATE FIT MITOCHONDRIA
4. ACTIVATE AMPK
5. CALORIE RESTRICTION AND CALORIE RESTRICTION MIMETICS
6. EXERCISE AND EXERCISE MIMETICS
7. BODY CLOCKÂ
8. FOLLOW A HEALTHY AGING EXPERT“
“In each of our cells are small energy generators called mitochondria. The health of our mitochondria determines the amount of adenosine triphosphate (ATP) they can produce from the calories we eat and oxygen we consume. Without robust mitochondria, cells cannot do as much work as they’re capable of and we need them to do so we can stay healthy. To achieve higher levels of performance we must optimize our mitochondria, the powerhouse of our cells, to produce energy. Cell function isn’t always the first place biohackers and nootropics enthusiasts start because it is challenging to notice a subjective boost in our mitochondrial function. Whether we can detect enhanced mitochondria subjectively or not, the science is pretty clear that healthy mitochondria play a role in supporting all indicators of cognition, physical performance, and aging. In a series of comprehensive posts, we will introduce scientifically-backed lifestyle changes and nootropics that up-regulate your mitochondrial function. In our last post, we went over how to use light and temperature to boost mitochondria. Now let’s tackle 5 more lifestyle habits we can implement to achieve healthier mitochondria.“
Mitochondria: Exploring 5 Lifestyle Habits to Benefit Cell Health
“Most individuals fail in maintaining their weight loss due to weight cycling, often referred to as Yoyo dieting. Weight regain often starts within the first year, and the pre-intervention weight is reached or even surpassed in the subsequent 2 to 5 years (Anderson et al., 2001; Weiss et al., 2007). Lean individuals that were voluntarily overfed with 50% additional calories for 3 days showed decreased pre-meal hunger and increased post-meal satiety (Cornier et al., 2004). In obese individuals that underwent weight loss, overfeeding did not diminish hunger or increase satiety. This absence of compensatory changes in hunger and satiety upon overfeeding likely contributes to an increased propensity for weight regain in obese individuals that undergo weight loss (Cornier et al., 2004). Overall, only 11% of the individuals with early-onset weight re-gain can achieve a subsequent body weight loss within that first year (Wing and Phelan, 2005).”
The results of this study seem to indicate that sleeping in the same room as parents and habits of feeding to sleep etc may contribute to lessor sleep quality in infants.
“Mean TST was 13h36min including 2h54min of naps; 20% of the infants had TST ≤12h/24h. About 46% did not present SOD or NW, 16% had frequent SODs and 22% had NW >1 night in 2. Parental presence, feeding to fall asleep and infant sleep arrangements were frequent in infants with short sleep duration (≤12h/24h), NW and SODs. Non-nutritive sucking was associated with risk of NW, SOD and TST >14h/24h. Parental room sharing was associated with NW.”
https://www.sciencedirect.com/science/article/abs/pii/S1389945719316417
“Accumulating evidences indicate that onset of myocardial infarction (MI) shows obvious circadian rhythmicity. Clinical studies have shown that MI occurred in the early morning has a poor prognosis. But the mechanisms involved still unknown. Here we show that the expression level of the Period 2 (per2), in the heart of mice is lower in the early morning than in the noon, while raising the expression of per2 in H9C2 cells and rat cardiomyocytes increased autophagy levels. Further studies indicated that overexpression of per2 after MI improved cardiac function through increasing the autophagy. In summary, this study identifies that circadian clock per2 may be a regulator of MI.”
“Fundamental cellular mechanisms such as nutrient sensing, DNA damage response pathways, and cell cycle regulation influence the aging process. Studies have shown that the nutrient sensory kinase, mTOR (TOR in yeast), regulates lifespan in response to nutrient availability. The mTOR kinase forms two distinct protein complexes: TORC1 and TORC2. TORC1, which is inhibited by rapamycin, regulates cell growth, proliferation, and metabolism. It is well established that TORC1 promotes protein translation via phosphorylation of ribosomal protein S6 kinase and the eIF4Eâ€binding protein (BP; Zoncu, Efeyan, & Sabatini, 2011). The TORC2 branch is less studied; however, TORC2 also plays important roles in metabolism, cell survival, and proliferation (Zoncu et al., 2011). Although the involvement of the TORC1 pathway in lifespan regulation is conserved among many species (i.e., TORC1 inhibition extends lifespan), it is still unclear how this pathway affects multiple downstream stress and damage response mechanisms.”
“The global population of individuals over the age of 65 is growing at an unprecedented rate and is expected to reach 1.6 billion by 2050. Most older individuals are affected by multiple chronic diseases, leading to complex drug treatments and increased risk of physical and cognitive disability. Improving or preserving the health and quality of life of these individuals is challenging due to a lack of wellâ€established clinical guidelines. Physicians are often forced to engage in cycles of “trial and error†that are centered on palliative treatment of symptoms rather than the root cause, often resulting in dubious outcomes. Recently, geroscience challenged this view, proposing that the underlying biological mechanisms of aging are central to the global increase in susceptibility to disease and disability that occurs with aging. In fact, strong correlations have recently been revealed between health dimensions and phenotypes that are typical of aging, especially with autophagy, mitochondrial function, cellular senescence, and DNA methylation. Current research focuses on measuring the pace of aging to identify individuals who are “aging faster†to test and develop interventions that could prevent or delay the progression of multimorbidity and disability with aging. Understanding how the underlying biological mechanisms of aging connect to and impact longitudinal changes in health trajectories offers a unique opportunity to identify resilience mechanisms, their dynamic changes, and their impact on stress responses. Harnessing how to evoke and control resilience mechanisms in individuals with successful aging could lead to writing a new chapter in human medicine.”
“Sequencing technologies have changed not only our approaches to classical genetics, but also the field of epigenetics. Specific methods allow scientists to identify novel genome-wide epigenetic patterns of DNA methylation down to single-nucleotide resolution. DNA methylation is the most researched epigenetic mark involved in various processes in the human cell, including gene regulation and development of diseases, such as cancer. Increasing numbers of DNA methylation sequencing datasets from human genome are produced using various platforms—from methylated DNA precipitation to the whole genome bisulfite sequencing. Many of those datasets are fully accessible for repeated analyses. Sequencing experiments have become routine in laboratories around the world, while analysis of outcoming data is still a challenge among the majority of scientists, since in many cases it requires advanced computational skills. Even though various tools are being created and published, guidelines for their selection are often not clear, especially to non-bioinformaticians with limited experience in computational analyses. Separate tools are often used for individual steps in the analysis, and these can be challenging to manage and integrate. However, in some instances, tools are combined into pipelines that are capable to complete all the essential steps to achieve the result. In the case of DNA methylation sequencing analysis, the goal of such pipeline is to map sequencing reads, calculate methylation levels, and distinguish differentially methylated positions and/or regions. The objective of this review is to describe basic principles and steps in the analysis of DNA methylation sequencing data that in particular have been used for mammalian genomes, and more importantly to present and discuss the most pronounced computational pipelines that can be used to analyze such data. We aim to provide a good starting point for scientists with limited experience in computational analyses of DNA methylation and hydroxymethylation data, and recommend a few tools that are powerful, but still easy enough to use for their own data analysis.”
“The AMP-activated protein kinase (AMPK) acts as a cellular energy sensor. Once switched on by increases in cellular AMP : ATP ratios, it acts to restore energy homeostasis by switching on catabolic pathways while switching off cell growth and proliferation. The canonical AMP-dependent mechanism of activation requires the upstream kinase LKB1, which was identified genetically to be a tumour suppressor. AMPK can also be switched on by increases in intracellular Ca2+, by glucose starvation and by DNA damage via non-canonical, AMP-independent pathways. Genetic studies of the role of AMPK in mouse cancer suggest that, before disease arises, AMPK acts as a tumour suppressor that protects against cancer, with this protection being further enhanced by AMPK activators such as the biguanide phenformin. However, once cancer has occurred, AMPK switches to being a tumour promoter instead, enhancing cancer cell survival by protecting against metabolic, oxidative and genotoxic stresses. Studies of genetic changes in human cancer also suggest diverging roles for genes encoding subunit isoforms, with some being frequently amplified, while others are mutated.”
“Caloric restriction was effective in decreasing body and fat weights, total cholesterol and LDL. These effects were totally or partially reversed after 30 days of refeeding (groups GRL). During liver perfusion, the high glucose output of the GRs was further enhanced by adrenaline (1 μM), but not by lactate infusion. In contrast, in groups G6L, G12 L, G6RL and G12RL glycogenolysis (basal and adrenaline-stimulated glucose output) was low and gluconeogenesis from lactate was significant. A twofold increase in liver content of PKA in group G6R suggests that liver sensitivity to glucagon and adrenaline was higher because of caloric restriction, resulting in enhanced glucose output.”
“Mitochondria are iconic structures in biochemistry and cell biology, traditionally referred to as the powerhouse of the cell due to a central role in energy production. However, modern-day mitochondria are recognized as key players in eukaryotic cell biology and are known to regulate crucial cellular processes, including calcium signalling, cell metabolism and cell death, to name a few. In this review, we will discuss foundational knowledge in mitochondrial biology and provide snapshots of recent advances that showcase how mitochondrial function regulates other cellular responses.”
“Antidepressant-like effects of ethanolic extract of Hericium erinaceus (HE) mycelium enriched in erinacine A on depressive mice challenged by repeated restraint stress (RS) were examined. HE at 100, 200 or 400 mg/kg body weight/day was orally given to mice for four weeks. After two weeks of HE administration, all mice except the control group went through with 14 days of RS protocol. Stressed mice exhibited various behavioral alterations, such as extending immobility time in the tail suspension test (TST) and forced swimming test (FST), and increasing the number of entries in open arm (POAE) and the time spent in the open arm (PTOA). Moreover, the levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were decreased in the stressed mice, while the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were increased. These changes were significantly inverted by the administration of HE, especially at the dose of 200 or 400 mg/kg body weight/day. Additionally, HE was shown to activate the BDNF/TrkB/PI3K/Akt/GSK-3β pathways and block the NF-κB signals in mice. Taken together, erinacine A-enriched HE mycelium could reverse the depressive-like behavior caused by RS and was accompanied by the modulation of monoamine neurotransmitters as well as pro-inflammatory cytokines, and regulation of BDNF pathways. Therefore, erinacine A-enriched HE mycelium could be an attractive agent for the treatment of depressive disorders.”
“Air pollution, such as haze or smog, is an evolving and increasingly significant problem around the world. A wide range of hazards of chronic air pollution in children include nocturnal cough, asthma, poor performance in neurobehavioral function, negative impact in cognitive development and harmful effects on brain development1,2,3,4,5. In particular, children represent a vulnerable segment of any population. They carry more risks of long term exposure to pollution over the course of their lives and are susceptible to acquiring chronic diseases in their developing lungs6,7,8,9,10,11. Use of masks and respirators can offer protection against air pollutants. However, the commercially available disposable particulate respirators, typically certified for surgical (which may only offer some barrier against larger particles) and occupational use, are mainly designed for and studied in adults. The test standards are specified according to adult breathing conditions and fit. There are to date, no masks designed for and evaluated in children. “
“Obesity and being overweight have become a worldwide epidemic affecting more than 1.9 billion adults and 340 million children. Efforts to curb this global health burden by developing effective long-term non-surgical weight loss interventions continue to fail due to weight regain after weight loss. Weight cycling, often referred to as Yoyo dieting, is driven by physiological counter-regulatory mechanisms that aim at preserving energy, i.e. decreased energy expenditure, increased energy intake, and impaired brain-periphery communication. Models based on genetically determined set points explained some of the weight control mechanisms, but exact molecular underpinnings remained elusive. Today, gene–environment interactions begin to emerge as likely drivers for the obesogenic memory effect associated with weight cycling. Here, epigenetic mechanisms, including histone modifications and DNA methylation, appear as likely factors that underpin long-lasting deleterious adaptations or an imprinted obesogenic memory to prevent weight loss maintenance.”
A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials – ScienceDirect
Highlights
•Older adults can benefit from either aerobic, resistance, or mind-body exercise.
•Exercise is a therapeutic ally to pharmacological treatment of clinical depression.
•Pooled NMA evidence demonstrates high compliance and tolerance of exercise.
•There is opportunity for patients to select their preferred type(s) of exercise.
•Clinicians should facilitate exercise prescription based on patient preference.
“Higher Dietary Inflammatory Index (DII®) scores are associated with increased morbidity and mortality. However, little is known about the effects of DII on mortality in Mediterranean countries. Therefore, in the present study, we aimed to investigate the potential association between DII scores and overall, cancer and cardiovascular disease (CVD) mortality in people living in a Mediterranean area.”
“Higher DII scores were associated with a significantly higher mortality risk, whereas the association with causeâ€specific mortality was less clear. These findings highlight the potential importance of diet in modulating inflammation and preventing death. ”
a pilot study using gastric mucosa infected with Helicobacter pylori
” Aberrant DNA methylation is induced by aging and chronic inflammation in normal tissues. The induction by inflammation is widely recognized as acceleration of age-related methylation. However, few studies addressed target genomic regions and the responsible factors in a genome-wide manner. Here, we analyzed methylation targets by aging and inflammation, taking advantage of the potent methylation induction in human gastric mucosa by Helicobacter pylori infection-triggered inflammation. “
“Mild cognitive impairment or cognitive impairment without dementia (CIND) is a health condition elderly people suffer from.
The condition causes memory loss and in extreme cases, it can progress to Alzheimer’s disease.
A new study shows that exercise may help elevate symptoms of the condition.”
https://conductscience.com/exercise-intervention-helps-slow-down-memory-loss/
No referral or benefit, I just found this super useful and it allows me to bring my fitbit weight and oura sleep into Samsung health and Google fit.
It also supports Suunto, Garmin and many others.
https://play.google.com/store/apps/details?id=nl.appyhapps.healthsync
” In mouse models of Alzheimer’s disease, the investigational drug candidates known as CMS121 and J147 improve memory and slow the degeneration of brain cells. Now, researchers have shown how these compounds can also slow aging in healthy older mice, blocking the damage to brain cells that normally occurs during aging and restoring the levels of specific molecules to those seen in younger brains.”
https://www.sciencedaily.com/releases/2019/12/191210134028.htm
Risk-Benefit Analysis
Forever Healthy Foundation gGmbH
Amalienbadstraße 41
D-76227 Karlsruhe, Germany
Low-level light therapy (LLLT) is the use of low incident levels of photon energy at a particular wavelength, targeting tissue to achieve a clinically useful local or systemic effect without the creation of heat (athermal) or damage (atraumatic) (Calderhead & Tanaka, 2017). LLLT has shown dramatic effects when used for wound healing, pain management, and various musculoskeletal conditions.
This review focuses on its potential use in skin rejuvenation. It has been shown that upon exposure to light, chromophores in the skin (mitochondrial cytochrome C, melanin, and protoporphyrins) absorb photons which lead to downstream alterations in physiology such as changes in cell proliferation, differentiation, migration, inflammatory mediators, and collagen production. It is supposed that these photobiomodulative effects have beneficial effects on the skin, leading to a more youthful appearance through increased collagen and elastin production, and a reduction in age spots and wrinkles.
This analysis seeks to answer the following questions:
https://brain.forever-healthy.org/display/EN/Skin+Rejuvenation+by+Low-Level+Light+Therapy
Risk-Benefit Analysis
Forever Healthy Foundation gGmbH
Amalienbadstraße 41
D-76227 Karlsruhe, Germany
Senolytics are agents that selectively induce apoptosis of senescent cells. Fisetin is a flavonoid polyphenol found in many types of fruits and vegetables (Arai et al., 2000) that is believed to act as a senolytic in addition to its numerous other known benefits. Although natural senolytics are less potent, compared to the targeted senolytics, they have lower toxicity and are thus, likely to be more readily translatable to clinical medicine. This RBA focuses on the risks and benefits of using fisetin as a senolytic rather than its more common use as a supplement.
This RBA seeks to answer the following questions:
https://brain.forever-healthy.org/display/EN/Fisetin+Senolytic+Therapy
Risk-Benefit Analysis
Forever Healthy Foundation gGmbH
Amalienbadstraße 41
D-76227 Karlsruhe, Germany
NAD+ is a pyridine nucleotide found in all living cells. It plays an important role in energy metabolism and is a substrate for several enzymes (including those involved in DNA repair). NAD+ levels may decline markedly with age (Massudi et al., 2012; Clement et al., 2019; Zhu et al., 2011) and restoring those levels to a youthful state is believed to have beneficial effects on health and longevity.
This analysis seeks to answer the following questions:
https://brain.forever-healthy.org/display/EN/NAD+Restoration+Therapy
“Key Learning Objectives:
– Understand the importance of a gut-brain communication system
– Learn about signaling pathways in the gut-brain axisLearn how the gut microbiota influences brain function
– Discover how the gut microbiota can be targeted to influence brain function
WHAT IS THE GUT-BRAIN AXIS?
The gut, its microbes, and the brain are connected by a complex communication and regulation system called the gut-brain axis. The gut-brain axis (also known as brain-gut axis, microbiota-gut-brain axis, gut-brain connection) is a bidirectional signaling network made up of neurons, hormones, immune cells, and microbial molecules.[1,2] It is part of a larger system that informs the brain of the internal state and health of our body. This sense is called interoception and it’s crucial for the maintenance of physiological balance in our body, a state known as homeostasis.[3] “
What is The Gut-Brain Axis? An Exploration of The Communication Pathways Between The Brain, The Gut, And The Microbiota
“Medicinal mushrooms have been used for hundreds of years, mainly in Asian countries, for treatment of infections. More recently, they have also been used in the treatment of pulmonary diseases and cancer. Medicinal mushrooms have been approved adjuncts to standard cancer treatments in Japan and China for more than 30 years and have an extensive clinical history of safe use as single agents or combined with radiation therapy or chemotherapy.More than 100 species of medicinal mushrooms are used in Asia. Some of the more commonly used species include Ganoderma lucidum (reishi), Trametes versicolor or Coriolus versicolor (turkey tail), Lentinus edodes (shiitake), and Grifola frondosa (maitake).Studies have examined the effects of mushrooms on immune response pathways and on direct antitumor mechanisms. The immune effects are mediated through the mushrooms stimulation of innate immune cells, such as monocytes, natural killer cells, and dendritic cells. The activity is generally considered to be caused by the presence of high-molecular-weight polysaccharides in the mushrooms, although other constituents may also be involved. Clinical trials in cancer patients have demonstrated that G. lucidum products are generally well tolerated.[1]Many of the medical and scientific terms used in this summary are hypertext linked (at first use in each section) to the NCI Dictionary of Cancer Terms, which is oriented toward nonexperts.”
Medicinal Mushrooms (PDQ®) – PDQ Cancer Information Summaries – NCBI Bookshelf
“The maternal gut microbiome significantly influences infant gut microbiome acquisition. Vertical transmission of the bacterial microbiome is substantially higher compared to vertical transmission of the virome. However, the degree of similarity between the maternal and infant gut bacterial microbiome and virome did not vary by delivery route. The greater similarity of the bacterial microbiome and virome between twin pairs than unrelated twins may reflect a shared environmental exposure. Thus, differences of the inter-generation transmissibility at birth between the major kingdoms of microbes indicate that the foundation of these microbial communities are shaped by different rules.”
“As the most abundant bioactive polyphenol in green tea, epigallocatechin gallate (EGCG) is a promising natural product that should be utilized in the discovery and development of potential drug leads. Due to its association with chemoprevention, EGCG may find a role in the development of therapeutics for prostate cancer. Natural products have long been employed as a scaffold for drug design, as their already noted bioactivity can help accelerate the development of novel treatments. Green tea and the EGCG contained within have become associated with chemoprevention, and both in vitro and in vivo studies have correlated EGCG to inhibiting cell growth and increasing the metabolic stress of cancer cells, possibly giving merit to its long utilized therapeutic use in traditional therapies. There is accumulating evidence to suggest that EGCG’s role as an inhibitor of the PI3K/Akt/mTOR signaling cascade, acting upon major axis points within cancer survival pathways. The purpose of this review is to examine the research conducted on tea along with EGCG in the areas of the treatment of and/or prevention of cancer. This review discusses Camellia sinensis, as well as the bioactive phytochemical compounds contained within. Clinical uses of tea are explored, and possible pathways for activity are discussed before examining the evidence for EGCG’s potential for acting on these processes. EGCG is identified as being a possible lead phytochemical for future drug design investigations.”
“Probiotic bacteria are increasingly gaining importance in human nutrition owing to their multifaceted health beneficial effects. Studies have also shown that probiotic supplementation is useful in mitigating age-associated oxi-inflammatory stress, immunosenescence, and gut dysbiosis thereby promoting health and longevity. However, our current understanding of the process of aging suggests a strong interrelationship between the accumulation of senescent cells and the development of aging phenotype, including the predisposition to age-related disorders. The present review studies the documented pro-longevity effects of probiotics and highlights how these beneficial attributes of probiotics could be related to the mitigation of cellular senescence. ”
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Comprehensive longitudinal study of epigenetic mutations in aging
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Milk exosomal miRNAs: potential drivers of AMPK-to-mTORC1 switching in β-cell de-differentiation of type 2 diabetes mellitus
“Persistent milk miRNA signaling adds a new perspective to the pathogenesis of T2DM and explains the protective role of breastfeeding but the diabetogenic effect of continued milk miRNA signaling by persistent consumption of pasteurized cow’s milk.”
Oxidative stress, inflammatory cytokines and body composition of master athletes: The interplay
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Oxidative stress, inflammatory cytokines and body composition of master athletes: The interplay
https://link.researcher-app.com/Phic
– via Researcher (@ResearcherApp)
We found in children, intervention duration <12 weeks yielded significant reductions in IGF-1, whilst paradoxically, in participants >18 years old, metformin intake significantly increased IGF-1. We suggest that caution be taken when interpreting the findings of this review, particularly given the discordant supplementation practices between children and adults.
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“These studies demonstrate an important link between the [pathological] accelerated ageing process and normal aging, and also expose the CSB protein as a key factor against cellular ageing” concludes Dr. Ricchetti.
https://medicalxpress.com/news/2019-12-identification-key-protein-linked-ageing.html
“Analysis of these data demonstrates that pineal peptides (epithalamin and epithalon) have a more pronounced geroprotective effect on the thymus as compared with those of the thymus peptides (thymalin and thymogen) on the pineal gland.”
https://www.mendeley.com/catalogue/specific-features-pineal-glandthymus-relationships-during-aging/
“The expression of this gene led to the appearance of telomerase activity in the fibroblasts, elongation of telomeres (to the size characteristic of the embryonic cells), and immortalization.”
“While these results reveal some heterogeneity in the reprogramming process with respect to telomere length, human somatic cells reprogrammed to pluripotency generally displayed elongated telomeres that suggest that they will not age prematurely when isolated from subjects of essentially any age.”
https://www.mendeley.com/catalogue/telomere-dynamics-human-cells-reprogrammed-pluripotency/
“We recently synthesized a pyrazole derivative of curcumin called CNB-001 that enhances the activity of Ca2+/calmodulin dependent protein kinase II (CaMKII). Since CaMKII plays a central role in long-term potentiation (LTP) and memory, it was asked if CNB-001 can facilitate the induction of LTP in rat hippocampal slices and enhance memory in a rat object recognition test. It is shown that CNB-001 enhances both LTP and memory”
https://www.mendeley.com/catalogue/pyrazole-derivative-curcumin-enhances-memory/
“Hericium erinaceus was used in traditional Chinese medicine for physiologically beneficial medicines. Recently, it has become a candidate in causing positive brain health-related activities. We previously reported that Hericium erinaceus mycelium ameliorates Alzheimer’s disease (AD)-related pathologies.”
“Aging is an important risk factor for several human diseases such as cancer, cardiovascular disease and neurodegenerative disorders, resulting from a combination of genetic and environmental factors (e.g., diet, smoking, obesity and stress), which, at molecular level, cause changes in gene expression underlying the decline of physiological function. Epigenetics, which include mechanisms regulating gene expression independently of changes to DNA sequence, regulate gene expression by modulating the structure of chromatin or by regulating the binding of transcriptional machinery to DNA. Several studies showed that an impairment of epigenetic mechanisms promotes alteration of gene expression underlying several aging-related diseases. Alteration of these mechanisms is also linked with changes of gene expression that occurs during aging processes of different tissues. In this review, we will outline the potential role of epigenetics in the onset of two age-related pathologies, cancer and cardiovascular diseases.”
“Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI.”
“The SMART App serves as a new approach for users, especially wet-bench scientists with no programming background, to analyze the scientific big data and facilitate data mining. The SMART App is available at http://www.bioinfo-zs.com/smartapp.”
https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-019-0316-3
“The unprecedented resolution of genome-wide interaction maps shows functional consequences that extend the initial thought of an efficient DNA packaging mechanism: gene regulation, DNA repair, chromosomal translocations and evolutionary rearrangements seem to be only the peak of the iceberg. One key concept emerging from this research is the topologically associating domains (TADs) whose functional role in gene regulation and their association with disease is not fully untangled.”
https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-019-0317-2
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