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Recent Longevity News for the week ending 11/16/22

Male fertility crash accelerating worldwide: study - Hill, 11/15/22 - "The rate of decline since 2000 has been a striking, the study found, with an observed 2.64 percent fall each year in the number of sperm per milliliter of semen — more than twice as large of a decline as that observed since 1978, according to The Guardian ... These compounds — found in everything from personal care products to food packaging — have particularly dire impacts on reproductive function, Swan noted. She specifically called out phthalates and bisphenols (BPA), compounds used as linings in products like water bottles and takeout containers"

This may be the best time to exercise to improve heart health: study - Hill, 11/15/22 - "Exercising in the morning is associated with the lowest risk of heart disease and stroke, according to new research on over 86,000 individuals ... Compared with individuals who were active midday, those most active around 8 am or 10 am had 11 percent and 16 percent lower risks of incident coronary artery disease, respectively. For women, risks were reduced by 22 percent and 24 percent at these times ... Participants most active in the late morning had a 17 percent reduced risk of stroke, while women who were more active in the late morning had a 35 percent lower risk of stroke"

Abstracts from this week:

α-ketoglutarate suppresses immediate early gene expression in cancer cells - Biochem Biophys Res Commun 2022 Nov 11 - "Cancer cells exhibit increased glutamine consumption compared to normal cells, supporting cell survival and proliferation. Glutamine is converted to α-ketoglutarate (αKG), which then enters the tricarboxylic acid cycle to generate ATP. Recently, therapeutic modulation of glutamine metabolism has become an attractive metabolic anti-cancer strategy ... Together, these findings indicate that therapeutic targeting of IEG dysregulation by αKG can be a potentially effective anti-cancer therapeutic strategy for glutamine metabolism inhibitors" - See alpha ketoglutarate at Amazon.com.

Cordycepin exhibits anti-fatigue effect via activating TIGAR/SIRT1/PGC-1α signaling pathway - Biochem Biophys Res Commun 2022 Nov 9 - "Fatigue, a most commonly sub-health condition, may cause people more susceptible to many diseases. Cordycepin, a principal active ingredient from Cordyceps militaris, exerts various pharmacological activities including anti-diabetes, anti-inflammatory, immunomodulatory and antioxidant effects. However, the anti-fatigue effect of cordycepin and specific mechanism remained unclear. This study aimed to investigate the beneficial effect of cordycepin on physical fatigue and elucidate the potential mechanism. 20 mg/kg, 40 mg/kg of cordycepin and 500 mg/kg taurine were respectively treated to mice for 28 days before weight-loaded swimming test. The results revealed that cordycepin significantly prolonged the weight-loaded swimming time of mice. Meanwhile, cordycepin decreased the levels of lactic acid, blood uric nitrogen, and malondialdehyde, and increased the contents of superoxide dismutase, glutathione, nicotinamide adenine dinucleotide phosphate, hepatic glycogen, muscle glycogen and ATP. The metabolomic study by GC-MS showed that eight biomarkers were found in livers, including L-lactic acid, L-asparagine, 3-phosphoglyceric acid, inosine, D-galactose, L-tyrosine, glyceric acid and L-threonine. There were seven biomarkers in gastrocnemius, including D-ribose-5-phosphate, acetic acid, propionic acid, butyric acid, palmitic acid, oxaloacetic acid and citric acid. The results of metabolomics indicated that cordycepin might relieve fatigue by regulating energy metabolism and pentose phosphate pathway. Furthermore, we found cordycepin significantly enhanced the protein levels of TIGAR, SIRT1, PGC-1α, NRF1 and TFAM in gastrocnemius of weight-loaded swimming mice. Taken together, the present study demonstrated that cordycepin possessed an anti-fatigue effect via activating TIGAR/SIRT1/PGC-1α signaling pathway. Our study indicated that cordycepin may be a potentially efficient candidate for fatigue" - See Cordyceps militaris at Amazon.com.

Metformin is Associated with Reduced COVID-19 Severity in Patients with Prediabetes - Diabetes Res Clin Pract 2022 Nov 15 - "Metformin use is associated with less severe COVID-19 in patients with prediabetes or PCOS" - See metformin at ReliableRX.

Hawthorn flavonoid ameliorates cognitive deficit in mice with Alzheimer's disease by increasing the levels of Bifidobacteriales in gut microbiota and docosapentaenoic acid in serum metabolites - Food Funct 2022 Nov 14 - "Hawthorn flavonoid (HF) exhibits potential benefits in Alzheimer's disease (AD), but its mechanism of action remains elusive ... Our results showed that HF reversed the gut microbiota disturbance and metabolic disorder in AD mice by increasing the proportions of Dubosiella, Alloprevotella, and Bifidobacterium and decreasing the proportions of Acinetobacter, as well as increasing the levels of docosapentaenoic acid (DPA), sphingolipid (SM), and phosphatidylcholine (PC). Notably, a positive correlation between DPA and Bifidobacterium was observed for the first time. Therefore, HF may serve as a promising dietary supplement for improving the symptoms of Alzheimer's disease" - See hawthorn betty extract at Amazon.com.

Nicotinamide riboside ameliorates high-fructose-induced lipid metabolism disorder in mice via improving FGF21 resistance in the liver and white adipose tissue - Food Funct 2022 Nov 14 - "Fructose has been reported to acutely elevate the circulating fibroblast growth factor 21 (FGF21) levels, which ultimately causes FGF21 resistance. FGF21 resistance is suggested to result in lipid metabolism disorder. Nicotinamide riboside (NR) can alleviate lipid metabolism disorder in mice. It is unknown whether NR supplementation would alleviate lipid metabolism disorder in high-fructose exposed mice via improving FGF21 resistance ... In conclusion, we found that NR supplementation could ameliorate high-fructose-induced lipid metabolism disorder by improving FGF21 resistance in the liver and WAT, which may be related to the regulation of inflammation mediated by the SIRT1/NF-κB signaling pathway" - See nicotinamide riboside at Amazon.com.

Live and pasteurized Akkermansia muciniphila attenuate hyperuricemia in mice through modulating uric acid metabolism, inflammation, and gut microbiota - Food Funct 2022 Nov 14 - "Akkermansia muciniphila (A. muciniphila) has been demonstrated to exhibit beneficial effects against various metabolic diseases, but whether A. muciniphila has an anti-hyperuricemia effect remains unexplored ... These findings suggest that both live or pasteurized A. muciniphila could effectively attenuate hyperuricemia by moderating uric acid metabolism and inflammation, and live bacteria exhibit additional beneficial effects on the gut microbiota. These findings highlight that A. muciniphila could be potentially developed as a probiotic or postbiotic to combat hyperuricemia" - See Akkermansia muciniphila at Amazon.com.

Advanced glycation end products in skeletal muscle health and sarcopenia: a systematic review of observational studies - Mech Ageing Dev. 2022 Nov 8 - "Advanced glycation end products (AGEs) and AGEs receptor (RAGE) may play a role in sarcopenia. This systematic review evaluated the associations between AGEs measured in tissues (skin) by autofluorescence (SAF) and/or circulation (blood, urine) and muscle health outcomes (strength, mass, function) and sarcopenia in observational studies ... Circulating AGEs were negatively associated with muscle strength and physical functioning (four studies) and predicted the risk of walking disability (one prospective study), and sarcopenia (one study) in older adults. The role of RAGE in muscle health was inconclusive ... SAF and circulating AGEs were negatively associated with muscle-related outcomes in adults aged ≥30 years in cross-sectional studies. This finding should be confirmed in well-designed prospective studies investigating sarcopenia, as AGEs represent a potentially modifiable target for intervention" - Note: AGEs were big in the early 90s. It just seems like people join the latest anti-aging bandwagon and forget about the old ones. AGE inhibitors like alt-711, deprenyl, anti-oxidants, AKG, NMN, rapamycin, senescent cells, telomeres, etc. just off the top of my head. There are a lot more areas. Too many look for that one single bullet. Lot of the current anti-aging gurus seem to be guilty of that.

Effects of fish oil on methotrexate-induced reproductive damage in rats - Andrologia 2022 Nov 11 - "Methotrexate (MTX) is a folic acid antagonist that is commonly used in paediatric and adult oncology to treat a variety of malignancies. Internal organs, including the testis, are severely cytotoxic and genotoxic to MTX. Omega-3, as an antioxidant, has been shown to protect rat testis tissue from injury. The effect of fish oil (FO) on MTX-induced reproductive damage in rats was investigated in this work ... All sperm quality measures were significantly lowered in the MTX group, while FO had a recovery effect. There were no notable variations in histopathology across groups except for germ cell thickness, which reduced considerably in the MTX group and recovered with FO treatment. As a result, FO has been shown to reduce testicular toxicity following MTX treatment in rats" - See omega-3 supplements at Amazon.com.

Benefits of SGLT2i in heart failure across a broad range of ejection fractions: new opportunities and future challenges - Eur Heart J. 2022 Nov 12 - "In the post-hoc meta-analysis of five trials of 21 947 participants, SGLT2i reduced the risk of CV death or hospitalization for HF (HR, 0.77; 95% CI, 0.72–0.82), CV death (HR, 0.87; 95% CI, 0.79–0.95), first hospitalization for HF (HR, 0.72; 95% CI, 0.67–0.78), and all-cause mortality (HR, 0.92; 95% CI, 0.86–0.99). The clinical benefits of SGLT2i were consistent across different patient subgroups, and extended to patients with LVEF >60% and those treated with other HF therapies" - See See empagliflozin inhousepharmacy.vu.

Krill oil protects dopaminergic neurons from age-related degeneration through temporal transcriptome rewiring and suppression of several hallmarks of aging - Aging (Albany NY) 2022 Nov 9 - "There is accumulating evidence that interfering with the basic aging mechanisms can enhance healthy longevity. The interventional/therapeutic strategies targeting multiple aging hallmarks could be more effective than targeting one hallmark. While health-promoting qualities of marine oils have been extensively studied, the underlying molecular mechanisms are not fully understood. Lipid extracts from Antarctic krill are rich in long-chain omega-3 fatty acids choline, and astaxanthin ... Krill oil rewires distinct gene expression programs that contribute to attenuating several aging hallmarks, including oxidative stress, proteotoxic stress, senescence, genomic instability, and mitochondrial dysfunction. Mechanistically, krill oil increases neuronal resilience through temporal transcriptome rewiring to promote anti-oxidative stress and anti-inflammation via healthspan regulating transcription factors such as SNK-1. Moreover, krill oil promotes dopaminergic neuron survival through regulation of synaptic transmission and neuronal functions via PBO-2 and RIM-1. Collectively, krill oil rewires global gene expression programs and promotes healthy aging via abrogating multiple aging hallmarks, suggesting directions for further pre-clinical and clinical explorations" - See krill oil products at Amazon.com.

Antioxidant Properties and Beneficial Cardiovascular Effects of a Natural Extract of Pomegranate in Healthy Volunteers: A Randomized Preliminary Single-Blind Controlled Study - Antioxidants (Basel) 2022 Oct 28 - "Pomegranates are known to possess anti-hypertensive, anti-atherogenic and cardioprotective effects mainly due to their pleiotropic effects on various cellular pathways, especially those triggered by oxidative stress ... Urinary total phenolics excretion and antioxidant capacity were significantly increased after 14 and 28 days of PE intake. At day 28, there were also statistically significant decreases in systolic and diastolic blood pressure (BP), pulse wave velocity, body fat and fat mass, as well as an increase in lean body mass. Significant changes in the placebo group were not found. Glucocorticoid levels showed a significant decrease in saliva cortisol at day 28 (morning) in the PE group, and cortisol/cortisone ratio was significantly decreased following 28 days of PE intake at morning, noon, and evening. Urine free cortisol was significantly reduced at day 14. These findings suggest that pomegranate extract intake may improve antioxidant and oxidative stress status and play a beneficial role in the attenuation of some cardiovascular risk factors" - See pomegranate extract at Amazon.com.

Therapeutic Effect of Curcumin on 5/6Nx Hypertriglyceridemia: Association with the Improvement of Renal Mitochondrial β-Oxidation and Lipid Metabolism in Kidney and Liver - Antioxidants (Basel) 2022 Nov 6 - "Chronic kidney disease (CKD) prevalence is constantly increasing, and dyslipidemia in this disease is characteristic, favoring cardiovascular events. However, the mechanisms of CKD dyslipidemia are not fully understood. The use of curcumin (CUR) in CKD models such as 5/6 nephrectomy (5/6Nx) has shown multiple beneficial effects, so it has been proposed to correct dyslipidemia without side effects ... Our results showed that CUR reversed the increase in liver and kidney damage and hypertriglyceridemia induced by 5/6Nx. CUR also reversed mitochondrial membrane depolarization and β-oxidation disorders in the kidney and the increased lipid uptake and the high levels of proteins involved in fatty acid synthesis in the liver and kidney. CUR also decreased lipogenesis and increased mitochondrial biogenesis markers in the liver. Therefore, we concluded that the therapeutic effect of curcumin on 5/6Nx hypertriglyceridemia is associated with the restoration of renal mitochondrial ß-oxidation and the reduction in lipid synthesis and uptake in the kidneys and liver" - See curcumin at Amazon.com.

Effects of curcumin, a bioactive component of turmeric, on type 2 diabetes mellitus and its complications: an updated review - Food Funct 2022 Nov 11 - "Type 2 diabetes mellitus (T2DM) is a substantial issue in public health. Recently, there has been considerable interest in the effectiveness of using herbal supplements for T2DM. Among the herbal supplements, turmeric (Curcuma longa L.) has been attracting an avalanche of attention owing to its main component, curcumin ... Studies on diabetic humans and animals have revealed that curcumin may have positive effects on oxidative stress and inflammation and may reduce fasting blood glucose levels, increase insulin sensitivity/secretion and regulate the lipid profile. Thus, it may prevent and treat diabetes by affecting various molecular targets" - See curcumin at Amazon.com.

Curcumin Represses Colorectal Cancer Cell Proliferation by Triggering Ferroptosis via PI3K/Akt/mTOR Signaling - Nutr Cancer 2022 Nov 8 - "Curcumin is known to suppress the progression of colorectal cancer by inhibiting cancer cell proliferation ... Curcumin triggers ferroptosis and suppresses proliferation of colorectal cancer cells by inhibiting the PI3K/Akt/mTOR signaling pathway. These results indicate its potential as a treatment against colorectal cancer." - See curcumin at Amazon.com.


Vitamin D status and leukocyte telomere length in middle childhood - Eur J Clin Nutr 2022 Nov 8 - "Short telomere length is associated with chronic diseases and decreased lifespan. Vitamin D and its binding protein (DBP) may maintain telomeres through anti-inflammatory actions, yet the role of vitamin D on telomere length is uncertain, especially in children ... Overall, 25(OH)D was not significantly associated with LTL. Nonetheless, among boys, 25(OH)D < 50 nmol/L was related to an adjusted 0.36 shorter LTL z-score (95% CI: -0.71, -0.01; P = 0.046) compared with 25(OH)D ≥ 75 nmol/L. There was no association among girls. DBP was not significantly related to LTL. Intervention studies are warranted to determine whether increasing vitamin D status enhances telomere length" - See vitamin D at Amazon.com.

Small-Scale Randomized Controlled Trial to Explore the Impact of β-Hydroxy-β-Methylbutyrate Plus Vitamin D3 on Skeletal Muscle Health in Middle Aged Women - Nutrients 2022 Nov 4 - "β-Hydroxy-β-methylbutyrate (HMB), a leucine metabolite, can increase skeletal muscle size and function ... intermuscular adipose tissue (IMAT) volume ... HMB + D decreased IMAT independent of exercise status and may prevent the loss or increase muscle size in a small cohort of sedentary middle-aged women" - See HMB at Amazon.com and vitamin D at Amazon.com.

Anti-diabetic drug metformin suppresses tumorigenesis through inhibition of mevalonate pathway enzyme HMGCS1 - J Biol Chem 2022 Nov 7 - "Metformin, an antidiabetic drug, shows some potent anti-tumor effects. However, the molecular mechanism of metformin in tumor suppression has not been clarified. Here we provided evidence using in vitro and in vivo data that metformin inhibited mevalonate pathway by downregulation of HMGCS1, a key enzyme in this pathway. Our results further demonstrated that metformin downregulated HMGCS1 expression through inhibition of transcription factor NRF2. Additionally, we determined that HMGCS1 was highly expressed in human liver and lung cancer tissues and associated with lower survival rates. In summary, our study indicated that metformin suppresses tumorigenesis through inhibition of the NRF2/HMGCS1 axis, which might be a potential target in cancer prevention and treatment." - See metformin at ReliableRX.

Resveratrol alleviates postpartum depression-like behavior by activating autophagy via SIRT1 and inhibiting AKT/mTOR pathway - Behav Brain Res 2022 Nov 7 - "Postpartum depression (PPD) causes maternal mortality, and has a high disability rate. In recent years, studies have suggested the Sirt1 gene to be involved in the pathogenesis of depression. Resveratrol (RSV), an activator of Sirt1, has been investigated in depressive behavior. However, its effect on PPD remains to be thoroughly elucidated ... RSV could alleviate postpartum depression-like behavior in mice by stimulating the SIRT1, induce autophagy and inhibit the AKT/ mTOR signaling pathway" - See resveratrol products at Amazon.com.

Relationship between different forms of dietary choline and ovarian cancer survival: findings from the ovarian cancer follow-up study, a prospective cohort study - Food Funct 2022 Nov 10 - "Choline has important and diverse functions in both cellular maintenance and growth. However, the relationships between the prediagnosis of the different forms of dietary choline intake and ovarian cancer (OC) survival are relatively unknown ... Higher lipid-soluble choline intake was significantly associated with better overall survival for patients with OC (Tertile 3 vs. Tertile 1: HR = 0.56; 95% CI: 0.34, 0.92; P trend = 0.02) in the fully adjusted model. Similar associations were observed for phosphatidylcholine intake (Tertile 3 vs. Tertile 1: HR = 0.55; 95% CI: 0.33, 0.91; P trend = 0.02). However, no associations were found between total water-soluble choline (free choline, phosphocholine, and glycerophosphocholine), sphingomyelin, and betaine intake and OC survival. Significant additive interactions between higher fat-soluble choline intake and positive expression of estrogen receptor and Wilms tumor-1 as well as higher phosphatidylcholine intake and positive expression of estrogen receptor and Wilms tumor-1 on OC survival were detected. Conclusions: Our findings indicate that prediagnosis, total lipid-soluble choline and phosphatidylcholine intake were associated with improved overall survival among OC patients" - See citicholine at Amazon.com.

Dietary Betaine Intake and Risk of Mortality in Patients with Coronary Artery Disease: The Prospective Guangdong Coronary Artery Disease Cohort - Br J Nutr 2022 Nov 9 - "Patients in the highest tertile of dietary betaine intake had a lower risk of all-cause (P=0.007) and cardiovascular death (P<0.001) than those in the lowest tertile after adjusting for age and sex, traditional cardiovascular risk factors and other potential confounders. After further adjusting for plasma methionine metabolites and vitamins, HRs across tertiles of dietary betaine intake were 1.00, 0.84 and 0.72 for all-cause mortality (P for trend=0.124), and 1.00, 0.77 and 0.55 for cardiovascular mortality (P for trend=0.021). Higher dietary betaine intake was associated with a decreased risk of cardiovascular death after fully adjustment for cardiovascular risk factors, other potential confounders and plasma methionine metabolites and vitamins. However, the association between dietary betaine intake and risk of all-cause mortality was not statistically significant after further adjusting for plasma methionine metabolites and vitamins" - See betaine anhydrous (TMG) at Amazon.com.

Structural Insights into Amelioration Effects of Quercetin and Its Glycoside Derivatives on NAFLD in Mice by Modulating the Gut Microbiota and Host Metabolism - J Agric Food Chem 2022 Nov 9 - "The sugar moieties of natural flavonoids determine their absorption, bioavailability, and bioactivity in humans. To explore structure-dependent bioactivities of quercetin, isoquercetin, and rutin, which have the same basic skeleton linking different sugar moieties, we systemically investigated the ameliorative effects of dietary these flavonoids on high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) of mice. Our results revealed that isoquercetin exhibits the strongest capability in improving NAFLD phenotypes of mice, including body and liver weight gain, glucose intolerance, and systemic inflammation in comparison with quercetin and rutin. At the molecular level, dietary isoquercetin markedly ameliorated liver dysfunction and host metabolic disorders in mice with NAFLD. At the microbial level, the three flavonoids compounds, especially isoquercetin, can effectively regulate the gut microbiota composition, such as genera Akkermansia, Bifidobacterium, and Lactobacillus, which were significantly disrupted in NAFLD mice. These comparative findings offer new insights into the structure-dependent activities of natural flavonoids for NAFLD treatment" - See quercetin at Amazon.com and rutin at Amazon.com.


Health Focus (Vitamin K):