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Recent Longevity News for the week ending 11/9/22

Moving the Needle: SGLT2 Inhibitor Role for Isolated Kidney Disease - Medscape, 11/4/22 - "In the new trial, EMPA-Kidney, treatment with empagliflozin 10 mg daily for a median of 2.0 years led to a significant 28% relative risk reduction in the primary combined endpoint in comparison with placebo" - See empagliflozin inhousepharmacy.vu.

Abstracts from this week:

Early or late-life treatment with acarbose or rapamycin improves physical performance and affects cardiac structure in aging mice - J Gerontol A Biol Sci Med Sci 2022 Nov 7 - "Pharmacological treatments can extend lifespan in mice. For optimal translation in humans, treatments should improve health during aging, and demonstrate efficacy when started later in life. Acarbose (ACA) and Rapamycin (RAP) extend lifespan in mice when treatment is started early or later in life. Both drugs can also improve some indices of healthy aging, although there has been little systematic study of whether health benefits accrue differently depending on the age at which treatment is started. Here we compare the effects of early (4 month) versus late (16 month) onset ACA or RAP treatment on physical function and cardiac structure in genetically heterogeneous aged mice. ACA or RAP treatment improve rotarod acceleration and endurance capacity compared to controls, with effects that are largely similar in mice starting treatment from early or late in life. Compared to controls, cardiac hypertrophy is reduced by ACA or RAP in both sexes regardless of age treatment onset. ACA has a greater effect on the cardiac lipidome than RAP, and effects of early life treatment are recapitulated by late life treatment. These results indicate that late life treatment with these drugs provide at least some of the benefits of life long treatment, although some of the benefits occur only in males, which could lead to sex differences in health outcomes later in life" - See Siromus (rapamycin) at ReliableRXPharmacy.

• Comparison of Glucose Lowering Effect of Metformin and Acarbose in Type 2 Diabetes Mellitus: A Meta-Analysis - PLoS One. 2015 - "The glucose lowering effects of metformin monotherapy and acarbose monotherapy are the same by direct comparison, while metformin is a little better by indirect comparison. This implies that the effect of metformin is at least as good as acarbose's"

Saffron extract (Safr'Inside™) improves anxiety related behaviour in a mouse model of low-grade inflammation through the modulation of the microbiota and gut derived metabolites - Food Funct 2022 Nov 7 - "Treatment of anxiety and depression predominantly centres around pharmacological interventions, which have faced criticism for their associated side effects, lack of efficacy and low tolerability. Saffron, which is reportedly well tolerated in humans, has been recognised for its antidepressant and anti-anxiety properties ... In a rodent model of low-grade chronic inflammation, we explored the impact of a saffron extract (Safr'Inside™) supplemented at a physiological dose, which equated to 22 ± 1.2 mg per day human equivalent dose for a person of 60 kg ... Time occupying the centre of the Open Field maze (OF) was increased by 62% in saffron supplemented animals. This improvement in anxiety-related behaviour coincided with gut microbial shifts, notably Akkermansia, Muribaculaceae, Christensenellacae and Alloprevotella which significantly increased in response to saffron supplementation. Akkermansia and Muribaculaceae abundance negatively correlated with the neurotoxic metabolite dimethylamine which was reduced in saffron supplemented animals. Brain proteomic analysis highlighted several significantly altered proteins including ketimine reductase mu-crystallin which also correlated with dimethylamine concentration. Both dimethylamine and ketimine reductase mu-crystallin were associated with OF performance. This may be indicative of a novel interaction across the gut-brain axis which contributes to anxiety-related disorders" - See saffron supplements at Amazon.com.

Effects of Coenzyme Q10 Supplementation on Lipid Profiles in Adults: A Meta-analysis of Randomized Controlled Trials - J Clin Endocrinol Metab 2022 Oct 7 - "CoQ10 supplementation decreased the TC, LDL-C, and TG levels, and increased HDL-C levels in adults, and the dosage of 400 to 500 mg/day achieved the greatest effect on TC" - See ubiquinol products at Amazon.com.

Resveratrol improves vascular endothelial dysfunction in the unpredictable chronic mild stress model of depression in rats by reducing inflammation - Behav Brain Res 2022 Nov 3 - "Chronic psychological stress may cause depression and it is a risk factor for vascular endothelial dysfunction. Inflammation may contribute to endothelial dysfunction. Resveratrol, which has antiinflammatory and vasculoprotective properties, has been reported its beneficial effects on endothelial dysfunction induced by hypertension, diabetes and, aging ... Our findings suggest that resveratrol exerted antidepressant-like effect and prevented vascular endothelial dysfunction by reducing systemic and peripheral inflammation in UCMS-induced depression in rats. Therefore, resveratrol may be a therapeutic option with a vasculoprotective effect in depression." - See resveratrol products at Amazon.com.

Resveratrol inhibits proliferation and induces apoptosis via the Hippo/YAP pathway in human colon cancer cells - Biochem Biophys Res Commun 2022 Oct 25 - "High malignancy and mortality in colon cancer require clarifying the underlying mechanisms of colon cancer carcinogenesis and exploring new targets or drugs for the clinical treatment of colon cancer. Resveratrol (Res), a natural compound, shows cytotoxicity against various tumors ... Our findings suggested that the anti-cancer activity of Res may be mediated via activating Hippo/YAP signaling and partially disturbing the interaction between YAP and TEAD. All this evidence supports that Res may be an efficacious drug for colon cancer treatment" - See resveratrol products at Amazon.com.

Association Between Coffee Consumption and Incident Atrial Fibrillation (from the Multi-Ethnic Study of Atherosclerosis [MESA]) - Am J Cardiol 2022 Nov 2 - "This study aimed to elucidate a potential dose-dependent relation between coffee intake and atrial fibrillation (AF) incidence in a multi-ethnic setting. Previous studies were comprised mainly of White populations, and an exploration of dose dependency is limited. To address these gaps, we analyzed the Multi-Ethnic Study of Atherosclerosis data, a prospective cohort study ... Subjects who drank ≥1 cup of coffee/week had a higher incidence of AF (adjusted hazard ratio 1.40, p = 0.015) than nonconsumers. Furthermore, in the secondary analysis, there was an overall trend, albeit not consistent, of increasing adjusted hazard ratio with progressively increasing doses of coffee in the following groups: 1 to 3 cups/month, 2 to 4 cups/week, 2 to 3 cups/day and ≥6 cups/day. Notably, AF incidence was highest (9.8%) for the group consuming the most coffee, that is, ≥6 cups/day (p = 0.02). Stratification by race/ethnicity suggested the results may be driven by White and Hispanic rather than Black or Chinese-American subgroups. In conclusion, the findings suggest an association between coffee consumption and incident AF in contrast to most previous studies" - Note: I'm not sure what they're saying here. It's only a problem if you're not white?

• Good news for coffee lovers: Daily coffee may benefit the heart - Science Daily, 3/24/22 - "Drinking coffee -- particularly two to three cups a day -- is not only associated with a lower risk of heart disease and dangerous heart rhythms but also with living longer ... Participants' average age was 57 years and half were women. In general, having two to three cups of coffee a day was associated with the greatest benefit, translating to a 10%-15% lower risk of developing coronary heart disease, heart failure, a heart rhythm problem, or dying for any reason ... The second study included 34,279 individuals who had some form of cardiovascular disease at baseline. Coffee intake at two to three cups a day was associated with lower odds of dying compared with having no coffee. Importantly, consuming any amount of coffee was not associated with a higher risk of heart rhythm problems, including atrial fibrillation (AFib) or atrial flutter, which Kistler said is often what clinicians are concerned about. Of the 24,111 people included in the analysis who had an arrhythmia at baseline, drinking coffee was associated with a lower risk of death. For example, people with AFib who drank one cup of coffee a day were nearly 20% less likely to die than non-coffee drinkers ... coffee beans actually have over 100 biologically active compounds. These substances can help reduce oxidative stress and inflammation, improve insulin sensitivity, boost metabolism, inhibit the gut's absorption of fat and block receptors known to be involved with abnormal heart rhythm ... In a third study, researchers looked at whether there were any differences in the relationship between coffee and cardiovascular disease depending on whether someone drank instant or ground coffee or caffeinated or decaf. They found, once again, two to three cups a day to be associated with the lowest risk of arrhythmias, blockages in the heart's arteries, stroke or heart failure regardless of whether they had ground or instant coffee ... Decaf coffee did not have favorable effects against incident arrhythmia but did reduce cardiovascular disease, with the exception of heart failure"
• Coffee Drinking Linked With Fewer Arrhythmias - Medscape, 5/8/20 - "on average each additional daily cup of coffee that people said they drank reduced the incidence of arrhythmic episodes by a statistically significant 3%, compared with those who drank fewer daily cups. The relationship held for people who reported drinking as many as five or six cups of coffee daily"
• Influence of coffee and caffeine consumption on atrial fibrillation in hypertensive patients - Nutr Metab Cardiovasc Dis. 2010 Feb 16 - "Coffee and caffeine consumption influence spontaneous conversion of atrial fibrillation. Normotensive non-habitual coffee consumers are more likely to convert arrhythmia within 48h from the onset of symptoms. Hypertensive patients showed a U-shaped relationship between coffee consumption and spontaneous conversion of AF, moderate coffee consumers were less likely to show spontaneous conversion of arrhythmia. Patients with left ventricular hypertrophy showed a reduced rate of spontaneous conversion of arrhythmia"

Effect of Coffee Consumption on Risk of Coronary Heart Disease in a Systematic Review and Meta-Analysis of Prospective Cohort Studies - Am J Cardiol 2022 Nov 2 - "Previous prospective studies have reported inconsistent findings on the association between coffee consumption and the risk of coronary heart disease (CHD). This study aimed to investigate their association using a meta-analysis of prospective studies ... In the main meta-analysis of all studies, no significant association between coffee consumption and the risk of CHD was observed (relative risk [RR] 1.05, 95% confidence interval [CI] 0.97 to 1.14, I2 = 64.9%). In the subgroup meta-analyses by gender, coffee consumption significantly increased the risk of CHD in men (RR 1.19, 95% CI 1.05 to 1.35, n = 17), whereas a nonsignificantly decreased risk of CHD was observed in women (RR 0.91, 95% CI 0.77 to 1.08, n = 11). Also, in the subgroup meta-analyses by follow-up period, coffee consumption significantly increased the risk of CHD in the follow-up of 20 years or longer (RR 1.16, 95% CI 1.06 to 1.27, n = 4) regardless of gender. In conclusion, in the current meta-analysis of prospective studies, we found that, overall, no significant association between coffee consumption and the risk of CHD was observed. However, coffee consumption showed a differential effect by gender, with an increased risk of CHD in men and a potentially decreased risk in women"

Rapamycin treatment early in life reprograms aging: hyperfunction theory and clinical practice - Aging (Albany NY) 2022 Oct 24 - "Making provocative headlines, three outstanding publications demonstrated that early-life treatment with rapamycin, including treatments during developmental growth, extends lifespan in animals, confirming predictions of hyperfunction theory, which views aging as a quasi-program (an unintended continuation of developmental growth) driven in part by mTOR. Despite their high theoretical importance, clinical applications of two of these studies in mice, Drosophila and Daphnia cannot be implemented in humans because that would require growth retardation started at birth. A third study demonstrated that a transient (around 20% of total lifespan in Drosophila) treatment with rapamycin early in Drosophila adult life is as effective as lifelong treatment, whereas a late-life treatment is not effective. However, previous studies in mice demonstrated that a transient late-life treatment is highly effective. Based on hyperfunction theory, this article attempts to reconcile conflicting results and suggests the optimal treatment strategy to extend human lifespan" - See Siromus at ReliableRXPharmacy.

Dietary supplementation of L-carnitine ameliorates metabolic syndrome independent of trimethylamine N-oxide produced by gut microbes in high-fat diet-induced obese mice - Food Funct 2022 Nov 4 - "Metabolic syndrome (MS) ... L-carnitine (0.5%-4%) reduced HFD-caused body-weight gain, visceral adipose tissue, glucose intolerance, hyperglycemia, HOMA-IR index, hyperlipemia, hypertension, and hyperuricemia. The elevation in the concentrations of IL-6, IL-1β, and TNF-α and decline in IL-10 in both serum and adipose tissue were also attenuated by L-carnitine. Furthermore, dietary L-carnitine increased the serum levels of TMAO produced by gut microbes. High-dose L-carnitine (2% and 4%), but not low-dose L-carnitine (0.2%-1%), notably modulated the composition of gut microbiota and partially attenuated HFD-induced gut microbiota dysbiosis. These results suggest that the ameliorative effect of L-carnitine on MS was independent of TMAO production and only partially related to the regulation of gut microbiota. This study provides crucial evidence for the utilization of L-carnitine as a safe and effective supplement for MS" - See L-carnitine at Amazon.com.

Low-Dose Empagliflozin as Adjunct to Hybrid Closed-Loop Insulin Therapy in Adults With Suboptimally Controlled Type 1 Diabetes: A Randomized Crossover Controlled Trial - Diabetes Care 2022 Nov 4 - "Empagliflozin at 2.5 and 5 mg increased time in range during hybrid closed-loop therapy by 11-13 percentage points compared with placebo in those who otherwise were unable to attain glycemic targets. Future studies are required to assess long-term efficacy and safety" - See empagliflozin inhousepharmacy.vu.

Network meta-analysis of sacubitril/valsartan for the treatment of essential hypertension - Clin Res Cardiol 2022 Nov 3 - "In hypertensive patients, 200 mg once daily of sacubitril/valsartan may exert a greater reduction in ambulatory blood pressure than 100 mg once daily and 200 mg once daily may not be inferior to 400 mg once daily. Moreover, it is not clear that sacubitril/valsartan lowers blood pressure more than an angiotensin receptor blocker"

Lycopene Alleviates Chronic Stress-Induced Liver Injury by Inhibiting Oxidative Stress-Mediated Endoplasmic Reticulum Stress Pathway Apoptosis in Rats - J Agric Food Chem 2022 Nov 1 - "LYC protects against CRS-induced liver injury by activating the Nrf2 signaling pathway, scavenging ROS, and further attenuating ERS-associated apoptosis pathways" - See lycopene at Amazon.com.

Testosterone Therapy in Prostate Cancer - Curr Opin Urol. 2022;32(6):598-606 - "The use of TTh in hypongonadal men with a localized PCa has been shown to have positive clinical outcomes without increasing the rate of disease progression or recurrence. Further research, in a randomized controlled setting, is warranted"

Luteolin can ameliorate renal interstitial fibrosis-induced renal anaemia through the SIRT1/FOXO3 pathway - Food Funct 2022 Nov 2 - "In vivo, haemoglobin and haematocrit were increased significantly, blood urea nitrogen and creatinine were decreased significantly, and the degree of renal interstitial injury and fibrosis was significantly alleviated in luteolin-treated mice compared with model mice. Erythropoietin (EPO) and hypoxia inducible factor 2A (HIF2A) levels were significantly increased and alpha smooth muscle actin (α-SMA), collagen I (COLI) and fibronectin (FN) levels were significantly decreased. Transcriptomic analysis revealed significant increases in sirtuin 1 (SIRT1) and forkhead box O3 (FOXO3) after luteolin intervention; these effects were validated in vitro and in vivo. Combined treatment with luteolin and the SIRT1 activator resveratrol or the SIRT1 inhibitor sirtinol and SIRT1-siRNA transfection revealed that blocking SIRT1 reduced FOXO3 expression and significantly decreased the benefits of luteolin, while resveratrol had the opposite effects. Molecular docking analysis indicated a stable conformation between luteolin and SIRT1. In vitro and in vivo systematic and transcriptomic studies showed that luteolin attenuates renal anaemia caused by renal fibrosis through the SIRT1/FOXO3 pathway" - See luteolin products at Amazon.com.

Increasing brain glucose uptake by Gypenoside LXXV ameliorates cognitive deficits in a mouse model of diabetic Alzheimer's disease - Phytother Res 2022 Nov 3 - "We have previously reported that Gypenoside LXXV (GP-75), a novel natural PPARγ agonist isolated from Gynostemma pentaphyllum, ameliorated cognitive deficits in db/db mice ... In summary, GP-75 ameliorated cognitive deficits in APP/PS1 and APP/PS1xdb/db mice by enhancing glucose uptake via activation of the PPARγ/Akt/GLUT4 signaling pathways" - See Gynostemma pentaphyllum at Amazon.com.

Comparing the effects of docosahexaenoic and eicosapentaenoic acids on cardiovascular risk factors: Pairwise and network meta-analyses of randomized controlled trials - Nutr Metab Cardiovasc Dis 2022 Sep 28 - "Our findings suggest that both EPA and DHA act similarly on the markers under study, with slight changes in plasma glucose, insulin, and LDL-C" - See omega-3 supplements at Amazon.com and docosahexaenoic acid at Amazon.com.

Biological effects of the olive tree and its derivatives on the skin - Food Funct 2022 Oct 25 - "Numerous studies have pointed out the protective effect of olive compounds on skin ageing, thanks to their role in the different mechanisms involved in the ageing process, such as reducing oxidative stress, increasing cell viability and decreasing histological alterations. With regard to their photoprotective effect, the olive tree and its fruit contain phenolic compounds which have a protective effect against radiation, such as low ultraviolet absorption and high antioxidant activity, acting as a protective factor against photocarcinogenesis. Similarly, the anti-tumour effects of olives have been studied at the level of the different compounds and extracts obtained from them, and their ability to selectively attack human melanoma cells has been observed. They have also shown antibacterial activity against microorganisms particularly implicated in skin infections, such as Escherichia coli, Candida albicans, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa and Proteus spp. Likewise, on healthy tissue, they have shown the ability to stimulate growth, migration and the expression of genes involved in cell differentiation, which favours the regeneration of skin wounds" - See olive leaf extract at Amazon.com.

Health Focus (Red Yeast Rice):