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Recent Longevity News for the week ending 12/21/22

DELIVER Subanalysis 'Seals Deal' for Dapagliflozin in HF - Medscape, 12/19/22 - "The DELIVER analysis found that the effects of dapagliflozin on reducing cardiovascular death and worsening HF were greatest in patients who had the most debilitating symptoms at baseline, measured as KCCQ total symptom score (TSS) as 63 or less, the lowest of three tertiles used in the analysis. At baseline, these patients had the highest rates of CV death or worsening HF than those in the other two tertiles: KCCQ-TSS of 63-84, and greater than 84 ... Compared with placebo, treated patients in the lowest KCCQ-TSS quartile had a 30% reduction in risk for the primary composite outcome, which consisted of time to first CV death or HF event (hazard ratio, 0.70; 95% confidence interval, 0.58-0.84; P < .001). In the second tertile, the relative risk reduction was 19% (HR, 0.81; 95% CI, 0.65-1.01; P < .006), and the highest quartile showed no significant difference between treatment and placebo (HR, 1.07; 95% CI, 0.83-1.37; P < .62)." - See dapagliflozin at reliablerxpharmacy.com.

Abstracts from this week:

Kaempferol attenuated diabetic nephropathy by reducing apoptosis and promoting autophagy through AMPK/mTOR pathways - Front Med (Lausanne) 2022 Nov 30 - "Renal podocyte injury, apoptosis and autophagy are involved in the occurrence and development of diabetic nephropathy (DN). Kaempferol (KPF) has the promotion of autophagy and inhibition of apoptosis properties in the development of miscellaneous diseases, but these functions in DN have not yet been elucidated ... In conclusion, KPF might have a protective effect on DN through reduced apoptosis and enhanced podocytes autophagy, which were correlated with regulating AMPK/mTOR pathways" - See Kaempferia parviflora at Amazon.com.

A Magtein®, Magnesium L-Threonate, -Based Formula Improves Brain Cognitive Functions in Healthy Chinese Adults - Nutrients 2022, 14(24), 5235 - "Magnesium is one of the most abundant essential minerals in the body. Magnesium supplements mostly have low bioavailability, except magnesium L-threonate. In 2010, a novel magnesium compound, magnesium L-threonate (Magtein®) was identified and was shown to raise the magnesium levels in the brain and neurons effectively. In this double-blind, placebo-controlled study, Magtein®PS, a magnesium L-threonate (Magtein®)- and phosphatidylserine-based formulation additionally containing vitamins C and D, was tested for its cognitive benefits in 109 healthy Chinese adults aged 18–65 years. Subjects were randomly assigned to receive either Magtein®PS or placebo (starch) capsules, at a dose of 2 g/day. “The Clinical Memory Test”, the standard test commonly used in Chinese hospitals and academic institutes for cognitive evaluation, was administered before and 30 days after subjects received the supplement. Subjects receiving Magtein®PS showed significant improvements over the control group in all five subcategories of “The Clinical Memory Test” as well as the overall memory quotient scores. The older participants showed more improvement than younger participants. Results indicated significant benefits of Magtein®PS in improving memory and cognition in healthy Chinese adults" - See Magtein at Amazon.com and phosphatidylserine at Amazon.com.

Melatonin promotes the restoration of bone defects via enhancement of miR-335-5p combined with inhibition of TNFα/NF-κB signaling - FASEB J 2023 Jan;37(1) - "Accelerating the repair of a bone defect is crucial clinically due to the increased prevalence of trauma, tumor, and infections in bone. Studies have found that excess acute and chronic inflammation attenuate osteogenic differentiation of BMSCs (bone marrow mesenchymal stem cells). Moreover, TNF-α and NF-κB could inhibit osteoblasts differentiation of BMSCs and promote osteoclastogenesis via multiple mechanisms, such as increasing osteoclast precursor cells and acting synergistically with cell cytokines. However, melatonin could inhibit the expression of TNFα/NF-κB and promote bone formation by activating the Wnt/β-catenin signaling pathway ... In conclusion, melatonin facilitates osteogenesis in bone defect healing by enhancing miR-335-5p expression and inhibiting the TNFα/NF-κB pathway." - See melatonin at Amazon.com.

Dietary leucine and fish oil cooperatively regulate skeletal myofiber type transformation via the CaMKII signaling pathway of pigs - Food Funct 2022 Dec 16. - "In conclusion, this study demonstrated that dietary Leu and FO co-regulated the transformation from glycolytic to oxidative skeletal myofiber type. It is hypothesized that there is an interaction between amino acids and polyunsaturated fatty acids, possibly via the CaMKII signaling pathway to upregulate MEF2 and mitochondrial biogenesis" - See leucine products at Amazon.com and omega-3 supplements at Amazon.com.

• Mitochondrial Biogenesis - Science Direct - "Mitochondrial biogenesis is a major adaption of skeletal muscle to exercise training and is induced by a complex interplay between numerous signaling pathways that respond to metabolic, mechanical, and hypoxic stresses that are generated within the myocyte during contraction."

Impact of cumulative hyperglycemic burden on the pancreatic cancer risk: A nationwide cohort study - Diabetes Res Clin Pract 2022 Dec 10 - "We aimed to investigate how much cumulative hyperglycemia exposure increases pancreatic cancer risk. ... The pancreatic cancer incidence increased significantly according to the hyperglycemic burden, defined as sustained hyperglycemic exposure, including pre-diabetic levels"

Quercetin-3-O-α-L-arabinopyranosyl-(1→2)-β-D-glucopyra-noside Isolated from Eucommia ulmoides Oliver Leaf Relieves Insulin Resistance in HepG2 cells via the IRS-1/PI3K/Akt/GSK-3β pathway - Biol Pharm Bull 2022 Dec 14 - "For nearly 2000 years, Eucommia ulmoides Oliver (EUO) has been utilized in traditional Chinese medicine (TCM) throughout China. Flavonoids present in bark and leaves of EUO are responsible for their antioxidant, anti-inflammatory, antitumor, anti-osteoporosis, hypoglycemic, hypolipidemic, antibacterial, and antiviral properties, but the main bioactive compound has not been established yet. In this study, we isolated and identified quercetin glycoside (QAG) from EUO leaves (EUOL) and preliminarily explored its molecular mechanism in improving insulin resistance (IR). The results showed that QAG increased uptake of glucose as well as glycogen production in the palmitic acid (PA)-induced HepG2 cells in a dose-dependent way. Further, we observed that QAG increases glucose transporters 2 and 4 (GLUT2 and GLUT4) expression and suppresses the phosphorylation of insulin receptor substrate (IRS)-1 at serine612, thus promoting the expression of phosphatidylinositol-3-kinase (PI3K) at tyrosine458 and tyrosine199, as well as protein kinase B (Akt) and glycogen synthase kinase (GSK)-3β at serine473 and serine9, respectively. The influence posed by QAG on the improvement of uptake of glucose was significantly inhibited by LY294002, a PI3K inhibitor. In addition, the molecular docking result showed that QAG could bind to insulin receptors. In summary, our data established that QAG improved IR as demonstrated by the increased uptake of glucose and glycogen production through a signaling pathway called IRS-1/PI3K/Akt/GSK-3β" - See olive leaf extract at Amazon.com.

Association of habitual coffee consumption and kidney function: A prospective analysis in the Rotterdam Study - Clin Nutr 2022 Nov 30 - "Population-based studies have suggested a protective effect of coffee against development of chronic kidney disease (CKD), possibly through coffee's anti-inflammatory and antioxidant compounds ... Participants' mean (SD) baseline age was 66 (10) years, 57% were women and median [IQR] coffee consumption was 3.0 [2.0, 5.0] cups/day. Those drinking more coffee were more likely to smoke, and to have type 2 diabetes (T2D) and obesity. Mean eGFR was 79 (15) ml/min per 1.73 m2. In the total study population, coffee was not associated with longitudinal eGFR during a median of 5.4 years of follow-up (β = 0.04 ml/min per 1.73 m2 per one cup/day [95% CI: -0.10,0.18]). However, among those aged >70 years, one additional coffee cup/day was associated with on average 0.84 (0.51,1.18) ml/min per 1.73 m2 higher longitudinal eGFR. Among obese participants this estimate was 0.32 (0.01,0.63). A protective trend was also observed among former smokers (0.17 [-0.03,0.39]) and those with T2D (0.42 [-0.05,0.88]). Coffee was not associated with longitudinal ACR (0.01 mg/ml [-0.01,0.02])"

Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin - Aging Cell 2022 Dec 14 - "Declining nicotinamide adenine dinucleotide (NAD+ ) concentration in the brain during aging contributes to metabolic and cellular dysfunction and is implicated in the pathogenesis of aging-associated neurological disorders. Experimental therapies aimed at boosting brain NAD+ levels normalize several neurodegenerative phenotypes in animal models, motivating their clinical translation. Dietary intake of NAD+ precursors, such as nicotinamide riboside (NR), is a safe and effective avenue for augmenting NAD+ levels in peripheral tissues in humans, yet evidence supporting their ability to raise NAD+ levels in the brain or engage neurodegenerative disease pathways is lacking. Here, we studied biomarkers in plasma extracellular vesicles enriched for neuronal origin (NEVs) from 22 healthy older adults who participated in a randomized, placebo-controlled crossover trial (NCT02921659) of oral NR supplementation (500 mg, 2x /day, 6 weeks). We demonstrate that oral NR supplementation increases NAD+ levels in NEVs and decreases NEV levels of Aβ42, pJNK, and pERK1/2 (kinases involved in insulin resistance and neuroinflammatory pathways). In addition, changes in NAD(H) correlated with changes in canonical insulin-Akt signaling proteins and changes in pERK1/2 and pJNK. These findings support the ability of orally administered NR to augment neuronal NAD+ levels and modify biomarkers related to neurodegenerative pathology in humans. Furthermore, NEVs offer a new blood-based window into monitoring the physiologic response of NR in the brain" - See nicotinamide riboside at Amazon.com.

Neat Tech Stuff / "How To's":

I bought two of these for a Murphy bed I installed in a remodeled bedroom. Love it.

Health Focus (Coffee/Caffeine):