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Recent Longevity News for the week ending 8/24/22

FDA approves first fast-acting oral drug for clinical depression - Hill, 8/22/22 - "A newly approved drug from Axsome Therapeutics, Auvelity, can improve symptoms of major depressive disorder (MDD) — also known as clinical depression — after one week of administration, making it the first and only oral rapid-acting drug approved for the disorder"

How do strong muscles keep your brain healthy? - MIT Technology Review, 8/22/22 - "Myokines are released into the bloodstream when your muscles contract, create new cells, or perform other metabolic activities. When they arrive at the brain, they regulate physiological and metabolic responses there, too. As a result, myokines have the ability to affect cognition, mood, and emotional behavior. Exercise further stimulates what scientists call muscle-brain “cross talk,” and these myokine messengers help determine specific beneficial responses in the brain. These can include the formation of new neurons and increased synaptic plasticity, both of which boost learning and memory ... In these ways, strong muscles are essential to healthy brain function ... Even moderate exercise can increase metabolism in brain regions important for learning and memory in older adults. And the brain itself has been found to respond to exercise in strikingly physical ways. The hippocampus, a brain structure that plays a major role in learning and memory, shrinks in late adulthood; this can result in an increased risk for dementia. Exercise training has been shown to increase the size of the hippocampus, even late in life, protecting against age-related loss and improving spatial memory"

Omega-3 Fatty Acids Protective Against Depressive Episodes? - Medscape, 8/19/22 - "In regard to onset of depressive episodes, estimates from the fully-adjusted model suggest that a higher consumption of omega-3 acids (total and subtypes) is associated with lower the risk for depressive episodes — with significant associations for omega-3 and alpha-linolenic acid" - See omega-3 supplements at Amazon.com.

Vitamin D Deficiency Clearly Linked to Inflammation - Medscape, 8/19/22 - "Vitamin D deficiency has a causative role in the systemic inflammation that commonly accompanies it, with inflammation declining, reflected by reductions in elevated C-reactive protein (CRP), as vitamin D levels increase to normal levels, new research shows ... This is the first study of its kind, and the first to show that the well-known relationship between vitamin D status and CRP is at least in part driven by vitamin D ... The analysis showed that genetically predicted serum 25(OH)D was associated with serum CRP in an L-shaped manner, with CRP levels, and hence inflammation, sharply decreasing in relation to increasing 25(OH)D concentration to normal levels ... However, the relationship was only significant among participants with 25(OH)D levels in the deficiency range (< 25 nmol/L), with the association leveling off at about 50 nmol/L of 25(OH)D, which is generally considered a normal level ... cell experiments have shown that active vitamin D can inhibit the production of pro-inflammatory cytokines, including TNF-alpha, interleukin (IL)-1b, IL-6, IL-8, and IL-12, and promote the production of IL-10, an anti-inflammatory cytokine" - See vitamin D at Amazon.com.

Rainwater Unsafe to Drink Amid ‘Forever Chemicals’: Study - Medscape, 8/15/22 - "the levels of PFOA and PFOS in rainwater often “greatly exceed” U.S. guidelines for drinking water, as well as guidelines across Europe. Atmospheric spread has led to soil being “ubiquitously contaminated” across the globe and the safe “planetary boundary for chemical pollution being exceeded,”"

Abstracts from this week:

Probiotics supplementation and brain-derived neurotrophic factor (BDNF): a systematic review and meta-analysis of randomized controlled trials - Nutr Neurosci 2022 Aug 22 - "Overall, meta-analysis of 11 trials (n = 648 participants) showed no significant changes in serum level of BDNF following probiotics. However, subgroup analysis revealed that probiotics increased BDNF levels in individuals suffering from neurological disorders (n = 214 participants; WMD = 3.08 ng/mL, 95% CI: 1.83, 4.34; P = 0.001; I2 = 7.5%; P-heterogeneity 0.34), or depression (n = 268 participants; WMD = 0.77 ng/mL, 95% CI: 0.07, 1.47; P = 0.032; I2 = 88.4%; P-heterogeneity < 0.001). Furthermore, a significant increase in BDNF levels was found in studies that administered the mixture of Lactobacillus and Bifidobacterium genera, and were conducted in Asia" - See probiotic supplements at Amazon.com.

Treatment with β-blocker nebivolol ameliorates oxidative stress and endothelial dysfunction in tenofovir-induced nephrotoxicity in rats - Front Med (Lausanne) 2022 Aug 4 - "Tenofovir disoproxil fumarate (TDF), a widely prescribed component in antiretroviral regimens, has been associated with nephrotoxicity. Nebivolol is a third generation selective β-1 adrenergic receptor blocker and may protect renal structure and function through the suppression of oxidative stress and enhancement of nitric oxide (NO) synthesis ... Nebivolol holds multifaceted actions that promote an advantageous option to slow the progression of kidney injury in tenofovir-induced nephrotoxicity"

Association between serum ferritin level and the various stages of non-alcoholic fatty liver disease: A systematic review - Front Med (Lausanne) 2022 Aug 3 - "Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder across the world, and non-invasive evaluation approaches are in need to assess NAFLD disease progression. Serum ferritin has been proposed as one of the biomarkers for NAFLD diagnosis in previous studies ... Most studies identified serum ferritin to be a predictor of advanced NAFLD, while several revealed the opposite end"

Effects of Resveratrol Against Induced Metabolic Syndrome in Rats: Role of Oxidative Stress, Inflammation, and Insulin Resistance - Evid Based Complement Alternat Med 2022 Aug 11 - "Metabolic syndrome (MS) is a serious health problem associated with an increase in risk factors for hepatic steatosis, which is the most common liver disease today. The goal of this study was to investigate the protective effects of resveratrol against metabolic alterations associated with a high-fat high-fructose diet (HFFD) ... Administration of resveratrol reduced liver steatosis, oxidative stress, and inflammatory state. Also, it improved lipid profile as well as insulin sensitivity and reverted alterations in hepatic mRNA expression levels of the tested genes. Based on these findings, resveratrol could be proposed as a therapeutic approach for MS prevention" - See resveratrol products at Amazon.com.

Taurine promotes estrogen synthesis by regulating microRNA-7a2 in mice ovarian granulosa cells - Biochem Biophys Res Commun 2022 Aug 6 - "These results suggest that taurine promotes E2 synthesis through p38/miR-7a/Glg1/Cyp19a1 signaling pathway, which is crucial to understand the function and mechanism of taurine on estrogen synthesis" - See taurine at Amazon.com.

Chemical Profiles and Antiobesity Effect of a Mixture of Astragalus membranaceus and Lithospermum erythrorhizon Extract in High Fat Diet Fed Mice - Evid Based Complement Alternat Med 2022 Aug 12 - "The present study aimed to evaluate the antiobesity potential and synergistic effects of ALM16, a mixture of Astragalus membranaceus (AM) and Lithospermum erythrorhizon (LE) extracts, in HFD-induced obese mice. C57BL/6 mice were fed a normal diet (ND), high-fat diet (HFD), HFD + AM, HFD + LE or HFD + ALM16 (50, 100, and 200 mg/kg) daily for 5 weeks. Compared to the ND group, HFD-fed mice showed significant increases in body weight, food efficiency ratio, weights of white adipose tissues, adipocytes size, liver weight, and hepatic steatosis grade. However, ALM16 significantly reduced those increases induced by HFD. Moreover, as compared to the HFD group, the ALM16 group significantly ameliorated serum levels of lipid profiles (TG, TC, HDL, and LDL), adipokines (leptin and adiponectin), and liver damage markers (AST and ALT levels). Notably, ALM16 was more effective than AM or LE alone and had a similar or more potent effect than Garcinia cambogia extracts, as a positive control, at the same dose. These results demonstrate that ALM16 synergistically exerts anti-obesity effects based on complementary interactions between each component. Also, metabolic profiling between each extract and the ALM16 was confirmed by UPLC-QTOF/MS, and the difference was confirmed by relative quantification" - See Astragalus at Amazon.com.

Low Xanthophylls, Retinol, Lycopene, and Tocopherols in Gray and White Matter of Brains with Alzheimer's Disease - J Alzheimers Dis 2022 Aug 16 - "AD brains had significantly lower levels of lutein, zeaxanthin, anhydrolutein, retinol, lycopene, and alpha-tocopherol, and significantly increased levels of XMiAD, an unidentified xanthophyll metabolite. No meso-zeaxanthin was detected. The overlapping protective roles of xanthophylls, carotenes, α- and γ-tocopherol are discussed"

Circulating vitamin C and digestive system cancers: Mendelian randomization study - Clin Nutr 2022 Aug 7 - "Genetically predicted higher circulating vitamin C showed a suggestive association with lower risk of small intestine and colorectal cancer after accounting for multiple testing. The odds ratio per 1 standard deviation increment in circulating vitamin C was 0.55 (95% confidence interval 0.32-0.94; P = 0.029) for small intestine cancer and 0.84 (95% confidence interval 0.73-0.96; P = 0.013) for colorectal cancer" - See vitamin C products at Amazon.com.

Rapamycin/metformin co-treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice - Aging Cell 2022 Aug 19 - "Rapamycin treatment has positive and negative effects on progression of type 2 diabetes (T2D) in a recombinant inbred polygenic mouse model, male NONcNZO10/LtJ (NcZ10). Here, we show that combination treatment with metformin ameliorates negative effects of rapamycin while maintaining its benefits. From 12 to 30 weeks of age, NcZ10 males were fed a control diet or diets supplemented with rapamycin, metformin, or a combination of both. Rapamycin alone reduced weight gain, adiposity, HOMA-IR, and inflammation, and prevented hyperinsulinemia and pre-steatotic hepatic lipidosis, but exacerbated hyperglycemia, hypertriglyceridemia, and pancreatic islet degranulation. Metformin alone reduced hyperinsulinemia and circulating c-reactive protein, but exacerbated nephropathy. Combination treatment retained the benefits of both while preventing many of the deleterious effects. Importantly, the combination treatment reversed effects of rapamycin on markers of hepatic insulin resistance and normalized systemic insulin sensitivity in this inherently insulin-resistant model. In adipose tissue, rapamycin attenuated the expression of genes associated with adipose tissue expansion (Mest, Gpam), inflammation (Itgam, Itgax, Hmox1, Lbp), and cell senescence (Serpine1). In liver, the addition of metformin counteracted rapamycin-induced alterations of G6pc, Ppara, and Ldlr expressions that promote hyperglycemia and hypertriglyceridemia. Both rapamycin and metformin treatment reduced hepatic Fasn expression, potentially preventing lipidosis. These results delineate a state of "insulin signaling restriction" that withdraws endocrine support for further adipogenesis, progression of the metabolic syndrome, and the development of its comorbidities. Our results are relevant for the treatment of T2D, the optimization of current rapamycin-based treatments for posttransplant rejection and various cancers, and for the development of treatments for healthy aging" - See metformin at ReliableRX and Siromus at ReliableRXPharmacy.

The safety and efficacy of probiotic supplementation for critically ill adult patients: a systematic review and meta-analysis - Nutr Rev 2022 Aug 19 - "Probiotics, however, provided a significant reduction in ICU-acquired infections (risk ratio .73" - See probiotic supplements at Amazon.com.

Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials - Nutr Rev 2022 Aug 19 - "From an energy perspective, the brain is very metabolically demanding. It is well documented that creatine plays a key role in brain bioenergetics. There is some evidence that creatine supplementation can augment brain creatine stores, which could increase memory ... Overall, creatine supplementation improved measures of memory compared with placebo (standard mean difference [SMD] = 0.29, 95%CI, 0.04-0.53; I2 = 66%; P = 0.02). Subgroup analyses revealed a significant improvement in memory in older adults (66-76 years) (SMD = 0.88; 95%CI, 0.22-1.55; I2 = 83%; P = 0.009) compared with their younger counterparts (11-31 years)" - See creatine at Amazon.com.

Metformin, testosterone, or both in men with obesity and low testosterone: A double-blind, parallel-group, randomized controlled trial - Metabolism 2022 Aug 16 - "Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index ... the HOMA-IR index decreased significantly in all active groups compared to placebo (metformin - 2.4, 95 % CI -4.1 to - 0.8, p = 0.004; testosterone - 2.7, 95 % CI -4.3 to - 1.1, p = 0.001; combination - 3.4, 95 % CI -5.0 to - 1.8, p < 0.001). Combination therapy was not superior to testosterone alone in decreasing insulin resistance (-0.7, 95 % CI -2.3 to +0.9, p = 0.383). Only the combination of metformin plus testosterone significantly increased total and free testosterone concentrations, compared to placebo. No significant changes in body composition (except for a higher decrease in fat mass in the metformin and combination group), metabolic variables, erectile function, or HRQoL were found with any treatment" - See metformin at ReliableRX.

Investigation of the effect of hesperidin on some reproductive parameters in testicular toxicity induced by Bisphenol A - Andrologia 2022 Aug 19 - "Bisphenol A (BPA) is one of the chemicals that cause dysfunction and infertility in testicles. Therefore, it is crucial to develop effective treatments against this damage. In this study, the effects of Hesperidin (HESP), a flavonoid in testicular toxicity induced by BPA in rats, on oxidative stress, inflammation, apoptosis, histological damage, spermatogenesis, steroidogenic enzymes and reproductive hormones were investigated ... Bisphenol A (BPA) is one of the chemicals that cause dysfunction and infertility in testicles. Therefore, it is crucial to develop effective treatments against this damage. In this study, the effects of Hesperidin (HESP), a flavonoid in testicular toxicity induced by BPA in rats, on oxidative stress, inflammation, apoptosis, histological damage, spermatogenesis, steroidogenic enzymes and reproductive hormones were investigated" - See hesperidin at Amazon.com.

Medicine-food herb: Angelica sinensis, a potential therapeutic hope for Alzheimer's disease and related complications - Food Funct 2022 Aug 19 - "Alzheimer's disease (AD) is a progressive neurodegenerative disease, which has brought a huge burden to the world. The current therapeutic approach of one-molecule-one-target strategy fails to address the issues of AD because of multiple pathological features of AD. Traditionally, the herb of Angelica sinensis (AS) comes from the root of an umbrella plant Angelica sinensis (Oliv.) Diels. As a typical medicine-food herb, studies have shown that AS can alleviate AD and AD-complications by multiple targets through the various foundations of pharmaceutical material and dietary supply basis ... AS contains many effective components, such as ligustilide, z-ligustilide, n-butylidenephthalide, α-pinene, p-cymene, myrcene, ferulic acid, vanillic acid and coniferyl ferulate. It is found that AS, AS-active compounds and AS-compound recipes mainly treat AD through neuroprotective, anti-inflammation, and anti-oxidant effects, improving mitochondrial dysfunction, anti-neuronal apoptosis, regulating autophagy, regulating intestinal flora and enhancing the central cholinergic system, which shows the multi-component and multi-target effect of AS. The role of dietary supplement components in AS for AD intervention is summarized, including vitamin B12, folic acid, arginine, and oleic acid, which can improve the symptoms of AD" - See dong quai at Amazon.com.

Real-World data on efficacy of L-glutamine in preventing sickle cell disease-related complications in pediatric and adult patients - Front Med (Lausanne) 2022 Aug 1 - "L-glutamine has been shown to play an important role in the regulation of oxidative stress which is one of the key contributors to the pathophysiology of sickle cell disease (SCD). In a Phase 3 clinical trial, L-glutamine demonstrated a significant reduction in SCD-related complications including vaso-occlusive crises (VOCs), hospitalizations, and acute chest syndrome (ACS) compared to placebo in patients with SCD ... Compared to baseline, patients had significantly fewer pain crises (median change from 3.0 to 0.0; P < 0.00001), hospitalizations (median change from 3.0 to 0.0; P < 0.00001), days of hospitalization (median change from 15.0 to 0.0; P < 0.00001), and blood transfusions (median change from 3.0 to 0.0; P < 0.00001) at 24, 48, and 72 weeks following L-glutamine therapy. Moreover, there was a drastic decrease in the number of ACS events during this time. A significant increase was observed in mean hemoglobin levels and hematocrit proportions from baseline to 72 weeks (P < 0.001). Conversely, compared to baseline, mean reticulocyte counts and lactate dehydrogenase (LDH) levels were considerably lower at follow-up time points (P = 0.003 and P < 0.001, respectively). No patient reported treatment-related adverse events" - See L-glutamine at Amazon.com.

Possible Mechanism of Hematocrit Elevation by Sodium Glucose Cotransporter 2 Inhibitors and Associated Beneficial Renal and Cardiovascular Effects - Circulation 2019 Apr 23 - "SGLT2 inhibitor therapy is associated with a modest increase in hematocrit (2%–4%) relative to placebo, and this effect is consistent for all 4 SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin)" - See empagliflozin inhousepharmacy.vu.

Effects of Sodium-Glucose Co-transporter 2 Inhibitors on Hemoglobin Levels: A Meta-analysis of Randomized Controlled Trials - Front Pharmacol 2021 - "Compared to control patients, SGLT2 inhibitors were shown to increase hemoglobin levels in patients with T2DM and chronic kidney disease (standard mean difference = 0.70" - See empagliflozin inhousepharmacy.vu.

Curcumin activates Nrf2/HO-1 signaling to relieve diabetic cardiomyopathy injury by reducing ROS in vitro and in vivo - FASEB J 2022 Sep - "The hallmark feature of Diabetes mellitus (DM) is hyperglycemia which can lead to excess production of reactive oxygen species (ROS) in the myocardium, contributing to diabetic cardiomyopathy (DCM) ... In conclusion, these findings conclusively infer that CUR activation of the Nrf2/HO-1 signaling pathway exerts myocardial protection by reducing ROS formation" - See curcumin at Amazon.com.

Iron Deficiency in Heart Failure and Effect of Dapagliflozin: Findings From DAPA-HF - Circulation 2022 Aug 16 - "Iron deficiency is common in heart failure and associated with worse outcomes. We examined the prevalence and consequences of iron deficiency in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) and the effect of dapagliflozin on markers of iron metabolism ... Transferrin saturation, ferritin, and hepcidin were reduced and total iron-binding capacity and soluble transferrin receptor increased with dapagliflozin compared with placebo ... Iron deficiency was common in DAPA-HF and associated with worse outcomes. Dapagliflozin appeared to increase iron use but improved outcomes, irrespective of iron status at baseline" - See dapagliflozin at reliablerxpharmacy.com.

Berberine Reduces Renal Cell Pyroptosis in Golden Hamsters with Diabetic Nephropathy through the Nrf2-NLRP3-Caspase-1-GSDMD Pathway - Evid Based Complement Alternat Med 2021 Oct 31 - "To observe the effect of berberine (BBR) on kidney cell pyroptosis in golden hamsters with diabetic nephropathy (DN) and to explore the molecular mechanism of its renal protection ... DN golden hamster kidney NLRP3-Caspase-1-GSDMD signalling was enhanced. BBR can reduce oxidative stress damage by regulating antioxidative Nrf2 and then regulating NLRP3-Caspase-1-GSDMD signalling to inhibit pyroptosis, antagonizing DN inflammation-induced damage" - See berberine at Amazon.com.

Astaxanthin Alleviates Nonalcoholic Fatty Liver Disease by Regulating the Intestinal Flora and Targeting the AMPK/Nrf2 Signal Axis - J Agric Food Chem 2022 Aug 16 - "Nonalcoholic fatty liver disease (NAFLD) is among the most prevalent chronic liver diseases around the globe. The accumulation of lipids in the liver and oxidative stress are important pathological mechanisms of NAFLD. Astaxanthin (AT) is a carotenoid extracted from shrimps and crabs with beneficial biological activities, including anti-oxidative and anti-inflammatory activities ... The in vitro study showed that AT considerably lowered the protein expression level of fatty acid synthetase (FAS), sterol regulatory element-binding protein-1c (SREBP-1c), and acetyl-COA carboxylase (ACC) and increased the protein expression of nuclear factor-E2 associated factor 2 (Nrf2) and AMP-activated protein kinase (AMPK) in oleic acid (OA) and palmitic acid (PA)-induced HepG2 cells. Additionally, mechanistic studies revealed that compound C (AMPK inhibitor, CC) inhibited the regulatory effect of AT on the SREBP-1c and Nrf2 signaling pathways. In conclusion, AT can inhibit the SREBP-1c, FAS, and ACC signaling pathways, activate the AMPK and Nrf2 signaling pathways, and improve the structure of intestinal flora" - See astaxanthin at Amazon.com.

Carnosine as a potential therapeutic for the management of peripheral vascular disease - Nutr Metab Cardiovasc Dis 2022 Jul 16 - "Peripheral vascular disease is growing in its burden and impact; however it is currently under researched, and there are a lack of strong, non-invasive therapeutic options for the clinicians. Carnosine is a dipeptide stored particularly in muscle and brain tissue, which exhibits a wide range of physiological activities, which may be beneficial as an adjunct treatment for peripheral vascular disease. Carnosine's strong anti-inflammatory, antioxidant and antiglycating actions may aid in the prevention of plaque formation, through protective actions on the vascular endothelium, and the inhibition of foam cells. Carnosine may also improve angiogenesis, exercise performance and vasodilatory response, while protecting from ischemic tissue injury ... carnosine may have a role as an adjunct treatment for peripheral vascular disease alongside typical exercise and surgical interventions, and may be used in high risk individuals to aid in the prevention of atherogenesis" - See carnosine at Amazon.com.

Effect of Chlorogenic Acid via Upregulating Resolvin D1 Inhibiting the NF-κB Pathway on Chronic Restraint Stress-Induced Liver Inflammation - J Agric Food Chem 2022 Aug 17 - "Chronic stress can cause chronic inflammatory injury to the liver. Chlorogenic acid (CGA) is known to have a wide range of biological activities and anti-inflammatory effects ... These results suggest that the protective effects of CGA mediate the NF-κB pathway by upregulating the generation of RvD1. Above all, this research demonstrates the liver protective effect of CGA and provides a potential treatment strategy for chronic inflammatory disease" - See chlorogenic acid at Amazon.com.

High HDL (High-Density Lipoprotein) Cholesterol Increases Cardiovascular Risk in Hypertensive Patients - Hypertension 2022 Aug 15 - "Emerging evidence suggests that elevated levels of HDL-C (high-density lipoprotein cholesterol) could be linked to an increased mortality risk. However, to the best of our knowledge, the relationship between HDL-C and specific cardiovascular events has never been investigated in patients with hypertension ... Our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C<40 mg/dL (low HDL-C); HDL-C between 40 and 80 mg/dL (medium HDL-C); and HDL-C>80 mg/dL (high HDL-C). At the follow-up analysis, adjusting for potential confounders, we observed a total of 245 cardiovascular events with a significantly increased risk of cardiovascular events in the low HDL-C group and in the high HDL-C arm compared with the medium HDL-C group. The spline analysis revealed a nonlinear U-shaped association between HDL-C levels and cardiovascular outcomes. Interestingly, the increased cardiovascular risk associated with high HDL-C was not confirmed in female patients"

A randomized open-labeled study to examine the effects of creatine monohydrate and combined training on jump and scoring performance in young basketball players - J Int Soc Sports Nutr 2022 Aug 8 - "Creatine monohydrate (CrM) supplementation has been shown to be an effective and safe nutritional supplement to improve performance; however, the impact of CrM supplementation in young basketball players is less clear ... CrM supplementation in conjunction with resistance and plyometric training increased the lower-limb ABK power and scoring performance in U16 basketball players" - See creatine at Amazon.com.

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