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Recent Longevity News for the week ending 10/19/22

Fasting and its possible role in longevity - YouTube, Good Morning America, Dr. David Sinclair of Harvard

Empagliflozin and Elderly Patients With Preserved Ejection Fraction Heart Failure: Is Age Just a Number? - Medscape, 10/17/22 - "Major molecular regulators of cellular lifespan are sirtuin-1 (SIRT1) and mammalian target of rapamycin complex 1 (mTORC1). In a nutrient-deficient or calorie-restricted state, SIRT1 activation, along with adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) set forth a cascade of downstream target activations culminating in deceleration of cell aging. Suppression of the mTORC1 pathway further augments SIRT1-activated autophagy, the lysosome-utilizing process of clearing misfolded proteins from the cytosol. Without healthy autophagy, oxidative stress contributes to impaired endothelial nitric oxide (NO) pathways, inflammation, cell death, fibrosis, and cardiomyopathy (adapted from Gevaert et al1). SGLT2 inhibitors are hypothesized to contribute to activation of SIRT1 and suppression of mTORC1 pathways.10 Akt = protein kinase B; HFpEF = heart failure with preserved ejection fraction; ROS = reactive oxygen species ... Aside from the obvious bedside clinical implications, the findings of Bohm et al[7] cause us to wonder more about the mechanistic impact of SGLT2 inhibition on multiple cardiovascular and noncardiovascular therapeutic targets. SGLT2 inhibitors induce glycosuria and reduce insulin levels, which promotes a ketogenic and fatty acid oxidation state, mimicking calorie restriction physiology, which has been associated with cellular stress resistance, attenuation of cellular senescence, and reduced oxidative stress-induced tissue damage.[9] Such pathway activation is hypothesized to assuage metabolic disease, alleviate endothelial and vascular inflammation, and mitigate the clinically observed arterial stiffness associated with the HFpEF syndrome" - See empagliflozin inhousepharmacy.vu.

Home-Based Transcranial Stimulation Succeeds for Major Depression - Medscape, 10/17/22 - "The primary outcome of Hamilton Rating Scale for Depression (HAMD) score improved significantly, from a mean of 19.12 at baseline to 5.33 after 6 weeks. At 3 months, the mean HAMD score was 5.65, and 78.2% of patients met the criteria for clinical remission (HAMD score less than 9). At 6 months, patients maintained this improvement, with a mean HAMD score of 5.43 and 73.9% of the participants in clinical remission. The majority of participants (24 of 26) completed the full 6-week treatment."

Have you exercised your body fat lately? - Washington Post, 10/14/22 - "The fat cells from the older, sedentary men showed relatively poor mitochondrial health, with fewer mitochondria than in the young men’s fat and less energy produced by each mitochondrion. But the physically active men’s fat cells held plenty of mitochondria, more even than in fat tissue from the young men, so that their fat cells, overall, were better supplied with energy. Their fat tissue also showed fewer signs of incipient inflammation than fat from the inactive men, whatever their ages ... “Exercise training meant more mitochondria and better functioning mitochondria” and, in essence, healthier fat, said Anders Gudiksen, a professor of cell biology at the University of Copenhagen, who led the study."

Abstracts from this week:

Antiskin Aging Effects of Indole Alkaloid N-Glycoside from Ginkgo Fruit ( Ginkgo biloba fruit) on TNF-α-Exposed Human Dermal Fibroblasts - J Agric Food Chem 2022 Oct 17 - "Human skin aging has internal and external factors, both of which are characterized by TNF-α overproduction. Therefore, we aimed to identify a natural product that suppresses the damage that occurs in cutaneous dermal fibroblasts exposed to TNF-α. The protective effects of the indole alkaloid N-glycoside, ginkgoside B dimethyl ester (GBDE), isolated from ginkgo fruit (Ginkgo biloba fruit) were evaluated in TNF-α stimulated human dermal fibroblasts (HDFs) ... GBDE also reduced the expression of COX-2 to 2.06 ± 0.12-fold (p < 0.001) and increased the expression of HO-1 to 10.64 ± 0.2-fold (p < 0.001). In addition, GBDE inhibited the expression of the pro-inflammatory cytokines (IL-8, 2.2 ± 0.0; IL-1β, 1.6 ± 0.0; IL-6, 2.0 ± 0.10-folds, p < 0.05). These results provide experimental evidence that GBDE can protect against skin damage, including aging" - See Ginkgo biloba at Amazon.com.

Ginsenoside Rg1 Inhibits STAT3 Expression by miR-15b-5p to Attenuate Lung Injury in Mice with Type 2 Diabetes Mellitus-Associated Pulmonary Tuberculosis - Evid Based Complement Alternat Med 2022 Oct 4 - "Thus, we conclude that ginsenoside Rg1 inhibits the STAT3 expression by miR-15b-5p to attenuate lung injury in mice with type 2 diabetes mellitus-associated pulmonary tuberculosis" - See ginseng at Amazon.com.

Hypoglycemic effect of the polysaccharides from Astragalus membranaceus on type 2 diabetic mice based on the "gut microbiota-mucosal barrier" - Food Funct 2022 Oct 3 - "Astragalus membranaceus polysaccharides (APP), the main active constituent, possess numerous bioactivities ... The results showed that APP improved glycolipid metabolism disorders, inflammation and oxidative stress levels, and organ injury in T2DM mice. Furthermore, the APP could protect the intestinal barrier by suppressing intestinal inflammation and oxidative stress levels, and strongly inhibited the potential intestinal pathogen Shigella with a reduction rate of 88.92%, and promoted the growth of beneficial bacteria Allobaculum and Lactobacillus by 11.72% and 30.70%, respectively. In addition, the antibiotic test indicated that the APP could repair intestinal barrier damage by remodeling some specific gut microbiota which may be their hypoglycemic mechanism. The results provide a theoretical basis for the development of APP as a novel prebiotic in functional food for diabetes" - See astragalus at Amazon.com.

Vitamin B12 administration prevents ethanol-induced learning and memory impairment through re-establishment of the brain oxidant/antioxidant balance, enhancement of BDNF and suppression of GFAP - Behav Brain Res 2022 Oct 12 - "There are growing evidence indicating that the adolescent brain is persistently affected by the use of psychostimulant agents. In this regard, alcohol drinking has become rather common among the adolescents in many societies during the last decade. It is currently well known that long-term ethanol exposure deteriorates various cognitive functions such as learning and memory. Mechanistically, these adverse effects have been shown to be mediated by oxidative damage to central nervous system. On the other hand, Vit-B12 is known to improve cognitive performance by suppression of oxidative parameters ... There are growing evidence indicating that the adolescent brain is persistently affected by the use of psychostimulant agents. In this regard, alcohol drinking has become rather common among the adolescents in many societies during the last decade. It is currently well known that long-term ethanol exposure deteriorates various cognitive functions such as learning and memory. Mechanistically, these adverse effects have been shown to be mediated by oxidative damage to central nervous system. On the other hand, Vit-B12 is known to improve cognitive performance by suppression of oxidative parameters" - See vitamin B12 at Amazon.com.

Deletion of monoamine oxidase A in a prostate cancer model enhances anti-tumor immunity through reduced immune suppression - Biochem Biophys Res Commun 2022 Oct 6 - "We have previously shown that monoamine oxidase A (MAO A) mediates prostate cancer growth and metastasis. Further, MAO A/Pten double knockout (DKO) mice were generated and demonstrated that the deletion of MAO A delayed prostate tumor development in the Pten knockout mouse model of prostate adenocarcinoma ... Thus, MAO A inhibitor may alleviate immune suppression, increase the antitumor immune response and be used for cancer immunotherapy" - Note: Deprenyl is an old time anti-aging drug but it's a MOQ B inhibitor. I don't know of any MAO A inhibitors.

• Monoamine oxidase inhibitors (MAOIs) - Mayo Clinic

Only virgin type of olive oil consumption reduces the risk of mortality. Results from a Mediterranean population-based cohort - Eur J Clin Nutr 2022 Oct 14 - "Daily moderate consumption of virgin OO (1 and 1/2 tablespoons) was associated with a one-third lower risk of all-cause as well as half the risk of cardiovascular mortality. These effects were not seen for common OO" - See olive leaf extract at Amazon.com.

Fish consumption, omega-3 fatty acid intake, and risk of pain: the Seniors-ENRICA-1 cohort - Clin Nutr 2022 Sep 15 - "Omega-3 fatty acids have anti-inflammatory and analgesic (anti-nociceptive) actions. However, the relation of habitual omega-3 fatty acid intake and fish consumption - its main food source - with pain remains largely unknown ... Higher oily fish consumption was associated with reduced pain incidence and worsening over 5 years [fully adjusted odds ratios (95% confidence interval) = 0.68 (0.50,0.94) and 0.70 (0.55,0.88) for every 25 g/day increment (1.5 servings/week), respectively]. Total and white fish consumption were not associated with pain. Higher marine omega-3 fatty acid intake was inversely associated with pain worsening [odds ratio (95% confidence interval) per 0.5 g/day increment = 0.83 (0.72,0.96)]. The corresponding associations for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were 0.53 (0.33,0.87) and 0.73 (0.57,0.94)" - See omega-3 supplements at Amazon.com.

Intermittent Fasting-Short- and Long-Term Quality of Life, Fatigue, and Safety in Healthy Volunteers: A Prospective, Clinical Trial - Nutrients 2022 Oct 10 - "Intermittent fasting (IF) is defined as an eating pattern without calorie restrictions, alternating between periods of fasting and eating. In the past decades IF has not only become a popular weight-reducing diet but is thought to improve Quality of Life (QoL) and fatigue ... IF according to the 16:8 regime over a fasting period of three months significantly improved several aspects of the QoL and decreased fatigue in healthy people, while maintaining a good safety profile. The practicability of this diet was also demonstrated for shift workers and people with a high percentage of active labour. Apart from the improvement in QoL and fatigue, the significant reduction in IGF-1, which can act as an accelerator of tumour development and progression, might be an indicator of the potential benefits of IF for patients with cancer"

Dose-Response to Sacubitril/Valsartan in Patients With Heart Failure and Reduced Ejection Fraction - J Am Coll Cardiol 2022 Oct 18 - "The average daily dose was 112 mg in Tertile 1 (low dose), 342 mg in Tertile 2 (moderate dose), and 379 mg in Tertile 3 (high dose). Similar changes in prognostic biomarkers were observed in all dose tertiles. Gains in Kansas City Cardiomyopathy Questionnaire-23 scores were comparable regardless of dose category. Consistent reverse cardiac remodeling in all dose categories occurred; the median absolute left ventricular EF improvement across HF dose groups was 9.3%, 8.7%, and 10.2%, for low, moderate, and high doses, respectively; similar improvements in left atrial and ventricular volumes and E/e' were also observed across dose categories"

Higher Total Cholesterol Concentration May Be Associated with Better Cognitive Performance among Elderly Females - Nutrients 2022 Oct 9 - "In females, higher total cholesterol was significantly associated with higher cognitive scores, particularly in the digit symbol substitution test (OR 0.51, 95% CI (0.36-0.72)) and the animal fluency test (OR 0.64, 95% CI (0.45-0.91)). This association remained significant in models adjusted for age, race, smoking status, education level, and chronic conditions (OR 0.40, 95% CI (0.25-0.63)). This association was not significant in males, however"

Resveratrol in the Hypothalamic Paraventricular Nucleus Attenuates Hypertension by Regulation of ROS and Neurotransmitters - Nutrients 2022 Oct 7 - "The hypothalamic paraventricular nucleus (PVN) is an important nucleus in the brain that plays a key role in regulating sympathetic nerve activity (SNA) and blood pressure. Silent mating-type information regulation 2 homolog-1 (sirtuin1, SIRT1) not only protects cardiovascular function but also reduces inflammation and oxidative stress in the periphery. However, its role in the central regulation of hypertension remains unknown. It is hypothesized that SIRT1 activation by resveratrol may reduce SNA and lower blood pressure through the regulation of intracellular reactive oxygen species (ROS) and neurotransmitters in the PVN ... Resveratrol within the PVN attenuates hypertension via the SIRT1/NF-κB pathway to decrease ROS and restore the balance of excitatory and inhibitory neurotransmitters" - See resveratrol products at Amazon.com.

Evening primrose seed extract rich in polyphenols modulates the invasiveness of colon cancer cells by regulating the TYMS expression - Food Funct 2022 Oct 14 - "The inhibition of metastasis correlated with a decrease in thymidylate synthetase (TYMS), which has recently been associated with metastatic phenotype development. Our results indicate that the EPE might be an effective anticancer agent in suppressing colon cancer metastasis regardless of the invasiveness cause. Based on these findings, we concluded that the used EPE extract rich in polyphenols inhibits cell invasion by TYMS downregulation" - See evening primrose oil at Amazon.com.

Influence of vitamin D on sarcopenia pathophysiology: A longitudinal study in humans and basic research in knockout mice - J Cachexia Sarcopenia Muscle 2022 Oct 13 - "Vitamin D deficiency affects muscle strength and may contribute to the onset of sarcopenia" - See vitamin D at Amazon.com.

Schisandra B, a representative lignan from Schisandra chinensis, improves cisplatin-induced toxicity: An in vitro study - Phytother Res 2022 Oct 12 - "Schisandrin B (Scheme B) is the most abundant and active lignan monomer isolated from Schisandra chinensis. At present, most reports focus on its cardioprotective and hepatoprotective effects, however, the related reports on gastrointestinal protective effects are still limited ... In conclusion, Scheme B might alleviate cisplatin-induced IEC-6 cell damage by inhibiting oxidative stress, apoptosis, inflammation, and repairing intestinal barrier function. The present research provides a strong evidence that Scheme B may be a useful modulator in cisplatin-induced intestinal toxicity" - See Schizandra at Amazon.com.

Taurine and N-acetylcysteine treatments prevent memory impairment and metabolite profile alterations in the hippocampus of high-fat diet-fed female mice - Nutr Neurosci 2022 Oct 12 - "Obesity constitutes a risk factor for cognitive impairment. In rodent models, long-term exposure to obesogenic diets leads to hippocampal taurine accumulation. Since taurine has putative cyto-protective effects, hippocampal taurine accumulation in obese and diabetic models might constitute a counteracting response to metabolic stress ... We tested the hypothesis that treatment with taurine or with N-acetylcysteine (NAC), which provides cysteine for the synthesis of taurine and glutathione, prevent high-fat diet (HFD)-associated hippocampal alterations and memory impairment ... NAC and taurine can prevent memory impairment, while only NAC prevents alterations of metabolite concentrations in HFD-exposed female mice" - See Ttaurine at Amazon.com and n-acetyl cysteine at Amazon.com.

Pterostilbene Prevents Tunicamycin-Induced Intestinal Barrier Damage by Targeting Endoplasmic Reticulum Stress, Oxidative Stress, Autophagy, and Gut Microbiota - J Agric Food Chem 2022 Oct 12 - "Endoplasmic reticulum (ER) stress is a crucial factor in the pathogenesis of intestinal diseases. Pterostilbene (PT) has been demonstrated to mitigate ER stress and protect against intestinal disorders ... In conclusion, PT alleviated TM-induced intestinal barrier damage by regulating ER homeostasis, oxidative stress, autophagic flux, and gut microbiota" - See pterostilbene at Amazon.com.

Lycopene ameliorates skin aging by regulating the insulin resistance pathway and activating SIRT1 - Food Funct 2022 Oct 13 - "Microvascular loss is one of the most important characteristics of skin aging and several microvascular activities play key roles in preserving skin health. In vitro, lycopene (Ly) reduced the contents of reactive oxygen species (ROS), β-galactosidase, and advanced glycosylation end products (AGEs), while increasing the contents of ATP and NAD+/NADH along with the mitochondrial membrane potential (MMP) ... In summary, all data demonstrated that Ly might reverse insulin resistance via SIRT1 during skin aging and promote microvascular neovascularization to protect aging skin" - See lycopene at Amazon.com.

Salvia hispanica L. (chia) seed improves liver inflammation and endothelial dysfunction in an experimental model of metabolic syndrome - Food Funct 2022 Oct 12 - "This study showed new aspects of liver inflammation and endothelial dysfunction in dyslipidemic insulin resistant rats chronically fed with a sucrose-rich diet. In addition, we demonstrated new properties and molecular mechanisms associated with beneficial effects on inflammation and endothelial dysfunction of chia seed as a therapeutic strategy" - See chia seeds at Amazon.com.

Olive leaf extract inhibits metastatic melanoma spread through suppression of epithelial to mesenchymal transition - Phytother Res 2022 Oct - "Olive tree leaves are an abundant source of bioactive compounds with several beneficial effects for human health, including a protective role against many types of cancer ... Our results demonstrated that OLE inhibited melanoma cells proliferation through cell cycle arrest and induction of apoptotic cell death. Moreover, OLE suppressed the migration, invasion, and colonies formation of human melanoma cells. Similar to our in vitro findings, we demonstrated that the oral administration of OLE inhibited cutaneous tumor growth and lung metastasis formation in vivo by modulating the expression of EMT related factors. In addition, the anti-proliferative and anti-invasive effects of OLE against melanoma were also related to a simultaneous targeting of mitogen-activated protein kinase and PI3K pathways, both in vitro and in vivo. In conclusion, our findings suggest that OLE has the potential to inhibit the metastatic spread of melanoma cells thanks to its multifaceted mechanistic effects, and may represent a new add-on therapy for the management of metastatic melanoma." - See olive leaf extract at Amazon.com.

Quercetin inhibits the amphiregulin/EGFR signaling-mediated renal tubular epithelial-mesenchymal transition and renal fibrosis in obstructive nephropathy - Phytother Res 2022 Oct 11 - "In UUO rats, quercetin reduced the area of fibrosis as well as inflammation, oxidative stress, and cell apoptosis. In cultured HK-2 cells, quercetin significantly ameliorated the EMT induced by TGF-β1, which was accompanied by increased amphiregulin (AREG) expression. Moreover, quercetin inhibited AREG binding to the EGFR receptor, thereby further affecting other downstream pathways. Quercetin may alleviate fibrosis in vitro and in vivo by inhibiting the activation of AREG/EGFR signaling indicating a potential therapeutic effect of quercetin in renal fibrosis" - See quercetin at Amazon.com.

Berberine plays a cardioprotective role by inhibiting macrophage Wnt5a/β-catenin pathway in the myocardium of mice after myocardial infarction - Phytother Res 2022 Oct 11 - "Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI ... In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/β-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI" - See berberine at Amazon.com.

Efficacy of a Proprietary Fenugreek Seed Extract ( Trigonella foenum-graecum, Furocyst®) in Women with Polycystic Ovary Syndrome (PCOS): a Randomized, Double-Blind, Placebo-Controlled Study - J Am Nutr Assoc 2022 Oct 11 - "Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenemia, a quite common heterogenous endocrine/hormonal disorder, and accompanied by elevated androgen level, menstrual irregularity, and hirsutism. The consequences include infertility or miscarriage. It is a challenging problem to the physicians. In a one-arm, non-randomized preliminary investigation in fifty premenopausal women, we demonstrated the efficacy of Furocyst®, a patented, standardized Trigonella foenum-graecum extract, in ameliorating the symptoms of PCOS over a period of 90 consecutive days ... The studies collectively demonstrated the efficacy of Furocyst® as a safe, natural phytochemical-based formulation to alleviate the symptoms of PCOS. No significant adverse events were observed" - See Furocyst® at Amazon.com.

Neat Tech Stuff / "How To's":

Nanoleaf LED shapes and light bars now sync with Corsair gaming products

Neoleaf Modular RGB Light Panels

Health Focus (Ginseng):