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Recent Longevity News for the week ending 1/18/23

Now that the pain from the aborted Whipple has subsided, I'm off narcotic pain killers and I've partially recovered from the resulting anemia (on top of the depressing weather), I've decided to keep my newsletter going for a while and give chemo a try. It's only three times per month for three months. My wife's boss's mother has survived five years with an oncologist at UCSD. That cut hurt and it was affecting my thinking. Scripps isn't even positive if it's pancreatic cancer or colo something (not colon cancer). It'd be stupid to throw in the cards. The tumor that showed up on the PET and CAT scans is just outside the pancreas. Talk to four different doctors in four different fields and they'll give you four different prognosis's. One doc said that if it's the colo one, it's easier to treat but the oncologist didn't have a comment on that. Everyone but the surgeon claims it's not that bad. Plus, I have so many accounts tied to my qualitycounts.com email address, it would take years to fix them all creating a nightmare for my wife. I should have planned ahead on that.

Think this doesn't hurt (it's my stomach, not a dirty picture. the top is my belly button) Stitches come out i a couple days. It's healing well. I looks a lot better this weekend.:

Can 6 Minutes of Intense Cycling Put the Brakes on Alzheimer's? - Medscape, 1/12/23 - "In a small study of healthy adults, 6 minutes of high-intensity cycling increased circulating levels of brain-derived neurotrophic factor (BDNF) to a significantly greater extent than prolonged light cycling or fasting ... Both intermittent fasting and exercise have previously been shown to have potent neuroprotective effects; and an acute upregulation of BDNF appears to be a common mechanistic link"

Some BP Meds Tied to Significantly Lower Risk for Dementia, Alzheimer's - Medscape, 1/10/23 - "Over the course of the study, some participants filled at least one prescription for a stimulating angiotensin II receptor type 2 and 4, such as angiotensin II receptor type 1 blockers, dihydropyridine calcium channel blockers, and thiazide diuretics ... Others participants filled a prescription for an inhibiting type 2 and 4 angiotensin II receptors, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and nondihydropyridine calcium channel blockers ... All these medications lower blood pressure, but they do it in different ways ... After adjustments, results showed that initiation of an antihypertensive medication regimen that exclusively stimulates, rather than inhibits, type 2 and 4 angiotensin II receptors was associated with a 16% lower risk for incident ADRD over a follow-up of just under 7 years (hazard ratio [HR], 0.84; ... However, "we're not suggesting [that all patients] have their regimen switched," he added ... That's because inhibiting medications still have an important place in the antihypertensive treatment armamentarium, Marcum noted. As an example, beta-blockers are used post heart attack"

It’s not just what you eat, but the time of day you eat it - Washington Post, 1/10/23 - "When you eat your meals is just one of many dietary factors that can influence your metabolic health. And for some people, like night-shift workers, it’s impossible not to consume meals late at night ... But for those whose schedules permit, research suggests that having your biggest meal of the day in the morning or afternoon rather than at night could be beneficial ... In a new study published in Obesity Reviews, scientists looked at data from nine rigorous clinical trials involving 485 adults. They found that people who were assigned to follow diets where they consumed most of their calories earlier in the day lost more weight than people who did the reverse. They also had greater improvements in their blood sugar, cholesterol levels and insulin sensitivity, a marker of diabetes risk."

Regular Vitamin D Supplements May Lower Melanoma Risk - Medscape, 1/12/23 - "The study, published December 28 in Melanoma Research, involved almost 500 individuals attending a dermatology clinic who reported on their use of vitamin D supplements ... Regular users had a significant 55% reduction in the odds of having a past or present melanoma diagnosis, while occasional use was associated with a nonsignificant 46% reduction. The reduction was similar for all skin cancer types" - See vitamin D at Amazon.com.

Low-Dose Chemo May Improve Survival in Advanced Cancer - Medscape, 1/12/23 - "Patients with advanced cancer often select a "more is better" standard-dose palliative chemotherapy approach instead of a low-dose therapy option ... The current study found that a low-dose strategy may improve survival for patients with advanced ovarian, pancreatic, and lung cancers, with less toxicity and lower costs"

Abstracts from this week:

Dietary choline intake is necessary to prevent systems-wide organ pathology and reduce Alzheimer's disease hallmarks - Aging Cell 2023 Jan 15; - "There is an urgent need to identify modifiable environmental risk factors that reduce the incidence of Alzheimer's disease (AD). The B-like vitamin choline plays key roles in body- and brain-related functions. Choline produced endogenously by the phosphatidylethanolamine N-methyltransferase protein in the liver is not sufficient for adequate physiological functions, necessitating daily dietary intake. ~90% of Americans do not reach the recommended daily intake of dietary choline ... Dietary choline deficiency altered hippocampal networks associated with microtubule function and postsynaptic membrane regulation. In plasma, dietary choline deficiency altered protein networks associated with insulin metabolism, mitochondrial function, inflammation, and fructose metabolic processing. Our data highlight that dietary choline intake is necessary to prevent systems-wide organ pathology and reduce hallmark AD pathologies" - See citicholine at Amazon.com.

Effect of mulberry leaf or mulberry leaf extract on glycemic traits: a systematic review and meta-analysis - Food Funct 2023 Jan 16 - "Mulberry leaf (ML) and mulberry leaf extract (MLE) have numerous biological properties, such as regulating sugar and lipid metabolism, reducing blood glucose, and increasing insulin secretion. The aim of this study was to perform a systematic review and meta-analysis of randomized clinical trials to examine the effect of ML/MLE supplementation on glycemic traits in adults, including fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), and fasting plasma insulin (FPI) ... Meta-analysis showed that ML/MLE supplementation resulted in a significant reduction in FBG by -0.47 mmol L-1, HbA1c by -2.92 mmol mol-1, and FPI by -0.58 μIU mL-1. In addition, subgroup analysis indicated that long-term supplementation of ML/MLE (≥8 weeks) was more effective for regulation of the glycemic traits in the non-healthy and baseline FPG >6.1 mmol L-1 subgroups. Glycemic regulation by ML/MLE may be attributed to the phytochemicals they contain, which are mainly 1-deoxynojirimycin, flavonoids, phenolics, and polysaccharides" - See mulberry leaf extract at Amazon.com.

Ginsenoside AD-2 Ameliorating Lipopolysaccharide-Induced Activation in HSC-T6 Cells and Carbon Tetrachloride-Induced Hepatic Fibrosis in Mice via Regulation of VD-VDR Axis - J Agric Food Chem 2023 Jan 16 - "Ginsenoside 25-hydroxy protopanaxadiol (AD-2) isolated from ginseng was proved to have anti-hepatic fibrosis (HF) effect in our previous study. But the mechanism is unknown. The present study investigated the anti-HF effects and mechanisms of AD-2 on the lipopolysaccharide (LPS)-induced activation in HSC-T6 cells and carbon tetrachloride (CCl4)-induced hepatic fibrosis (HF) in mice. Results showed that AD-2 significantly inhibited the LPS-induced activated HSC-T6 cells in vitro and markedly reduced the serum transaminase and hydroxyproline levels, pathological changes, and hepatic body ratio in CCl4-induced HF mice, indicating AD-2 ameliorated liver injury and reversed HF notably. Moreover, AD-2 decreased the expression of TGF-β1, α-SMA, and MMP2, and maintained TIMP1/MMP9 in balance with the level of vitamin D (VD) and the expression of VD nuclear receptor (VDR) and Sirt3 increased. In conclusion, the anti-HF mechanism of AD-2 is related to the inhibition of HSC activation, promotion of collagen degradation, and regulation of the VD/VDR axis" - See ginseng at Amazon.com.

Curcumin suppresses cell proliferation and reduces cholesterol absorption in Caco-2 cells by activating the TRPA1 channel - Aging (Albany NY) 2023 Jan 11 - Lipids Health Dis 2023 Jan 14 -0 "Curcumin (Cur) is a bioactive dietary polyphenol of turmeric with various biological activities against several cancers. Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths. Intestinal cholesterol homeostasis is associated with CRC. Chemotherapy for CRC is related to varied adverse effects. Therefore, natural products with anti-cancer properties represent a potential strategy for primary prevention of CRC ... Cur inhibits cell proliferation and reduces cholesterol absorption in Caco-2 cells through the Ca2+/PPARγ/SP-1/SREBP-2/NPC1L1 signaling by activating the TRPA1 channel, suggesting that Cur can be used as a dietary supplement for the primary prevention of CRC. In Caco-2 cells, Cur first stimulates calcium influx by activating the TRPA1 channel, further upregulates PPARγ and downregulates SP-1/SREBP-2/NPC1L1 signaling pathway, and finally inhibits the absorption of cholesterol. TRPA1, transient receptor potential cation channel subfamily A member 1; NPC1L1, Niemann-Pick C1-like 1; PPARγ, peroxisome proliferator-activated receptor gamma; SP-1, specificity protein-1; SREBP-2, sterol regulatory element-binding protein-2; Cur, curcumin" - See curcumin at Amazon.com.

Lithium treatment extends human lifespan: findings from the UK Biobank - "therapeutic supplementation of lithium linked to decreased mortality (p = 0.0017) of individuals diagnosed with affective disorders. Subsequent multivariate survival analyses reveal lithium to be the strongest factor in regards to increased survival effects (hazard ratio = 0.274 [0.119-0.634 CI 95%, p = 0.0023]), corresponding to 3.641 times lower (95% CI 1.577-8.407) chances of dying at a given age for lithium users compared to users of other anti-psychotic drugs. While these results may further support the use of lithium as a geroprotective supplement, it should be noted that doses applied within the UK Biobank/NHS setting require close supervision by qualified medical professionals" - See lithium supplements at Amazon.com.

The Association of Vitamin D Status with Mild Cognitive Impairment and Dementia Subtypes: A Cross-Sectional Analysis in Dutch Geriatric Outpatients - J Alzheimers Dis 2023 Jan 7 - "We observed significantly lower 25(OH)D serum levels in both AD and VaD patients compared to no-dementia patients, but no significant differences between MCI and Lewy body and mixed dementia subtypes in this cross-sectional study of a geriatric outpatient clinic population" - See vitamin D at Amazon.com.

Oral anticoagulants: A plausible new treatment for Alzheimer's disease? - Br J Pharmacol 2023 Jan 12 - "Most studies reported a compelling decreased incidence of composite dementia in anticoagulated atrial fibrillation individuals, with the highest benefit for direct oral anticoagulants"

Little late on this one. I just added that pub to my RSS feed:

Role and Therapeutic Potential of Melatonin in Various Type of Cancers - Onco Targets Ther 2021 Mar 18 - "Cancer is a large group of diseases and the second leading cause of death worldwide. Lung, prostate, colorectal, stomach, and liver cancers are the most common types of cancer in men, whereas breast, colorectal, lung, cervical, and thyroid cancers are the most common among women. Presently, various treatment strategies, including surgical resection combined with chemotherapy, radiotherapy, nanotherapy, and immunotherapy, have been used as conventional treatments for patients with cancer. However, the clinical outcomes of advanced-stage disease remain relatively unfavorable owing to the emergence of chemoresistance, toxicity, and other undesired detrimental side effects. Therefore, new therapies to overcome these limitations are indispensable. Recently, there has been considerable evidence from experimental and clinical studies suggesting that melatonin can be used to prevent and treat cancer. Studies have confirmed that melatonin mitigates the pathogenesis of cancer by directly affecting carcinogenesis and indirectly disrupting the circadian cycle. Melatonin (MLT) is nontoxic and exhibits a range of beneficial effects against cancer via apoptotic, antiangiogenic, antiproliferative, and metastasis-inhibitory pathways. The combination of melatonin with conventional drugs improves the drug sensitivity of cancers, including solid and liquid tumors" - See melatonin at Amazon.com.

New Insights into How Melatonin Ameliorates Bisphenol A-Induced Colon Damage: Inhibition of NADPH Oxidase - J Agric Food Chem 2023 Jan 12 - "Conclusively, our finding suggested that MT can ameliorate BPA-induced colonic DNA damage by scavenging NOX-derived ROS, which further attenuates G2/M cell cycle arrest dependent on the ATM-Chk1/2-p53 axis" - See melatonin at Amazon.com.

Fisetin, a dietary flavonoid, increases the sensitivity of chemoresistant head and neck carcinoma cells to cisplatin possibly through HSP90AA1/IL-17 pathway - Phytother Res 2023 Jan 11 - "Cisplatin (DDP) resistance is a bottleneck in the treatment of head and neck cancer (HNC), leading to poor prognosis. Fisetin, a dietary flavonoid, has low toxicity and high antitumor activity with unclear mechanisms ... Administration of fisetin increased the sensitivity of chemoresistant cells (Cal27/DDP and FaDu/DDP) to DDP, accompanied by the downregulation of HSP90AA1 and IL-17. HSP90AA1 silencing increases the sensitivity of DDP-resistant cells to DDP, which was mediated by IL-17. In summary, fisetin might inhibit the chemoresistance of HNC cells to DDP by targeting the HSP90AA1/IL-17 pathway. Several hub genes might be the targets of fisetin for reversing DDP-resistance in HNC cells and might also serve as prognostic factors and therapeutic targets for HNC" - See fisetin at Amazon.com.

Ginsenoside Rc Alleviates Myocardial Ischemia-Reperfusion Injury by Reducing Mitochondrial Oxidative Stress and Apoptosis: Role of SIRT1 Activation - J Agric Food Chem 2023 Jan 10 - "Myocardial ischemia-reperfusion (MI/R) injury occurs when coronary blood supply is impaired and then re-established, leading to additional injury to the myocardial tissue, including mitochondria oxidative stress and apoptosis ... In conclusion, our findings demonstrate that ginsenoside Rc ameliorated MI/R injury by reducing mitochondrial oxidative stress and apoptosis, at least in part, by activating SIRT1" - See ginseng at Amazon.com.

Ginsenoside Compound K Ameliorates Osteoarthritis by Inhibiting the Chondrocyte Endoplasmic Reticulum Stress-Mediated IRE1α-TXNIP-NLRP3 Axis and Pyroptosis - J Agric Food Chem 2023 Jan 11 - "Osteoarthritis (OA) is a common joint disease, and studies have reported that the endoplasmic reticulum stress (ERS) in chondrocytes caused by the cartilage tissue damage could mediate the activation of Nod-like receptor protein 3 (NLRP3) inflammasomes through inositol-requiring enzyme 1 alpha (IRE1α) and thioredoxin interacting protein (TXNIP). Ginsenoside compound K (CK) has an inhibitory effect on IRE1α activation ... In conclusion, CK hindered OA progression by inhibiting the ERS-IRE1α-TXNIP-NLRP3 axis. Overall, our data indicate that CK could be useful in the treatment of OA and other chronic inflammatory diseases." - See ginseng at Amazon.com.

Sesamolin Attenuates Kidney Injury, Intestinal Barrier Dysfunction, and Gut Microbiota Imbalance in High-Fat and High-Fructose Diet-Fed Mice - J Agric Food Chem 2023 Jan 11 - "This study investigated the effects of sesamolin on kidney injury, intestinal barrier dysfunction, and gut microbiota imbalance in high-fat and high-fructose (HF-HF) diet-fed mice and explored the underlying correlations among them. The results indicated that sesamolin suppressed metabolic disorders and increased renal function parameters. Histological evaluation showed that sesamolin mitigated renal epithelial cell degeneration and brush border damage ... Thus, sesamolin may be a potential dietary supplement for protection against obesity-associated kidney injury" - See sesame seed oil at Amazon.com.

Probiotic supplements are effective in people with cognitive impairment: a meta-analysis of randomized controlled trials - Nutr Rev 2023 Jan 11 - "Cognitive function is a significant concern among the elderly and has a major negative effect on their quality of life. Probiotics have a positive effect on improving cognition, but the exact nature of the association between probiotic supplements and cognitive function is poorly understood ... According to this meta-analysis, probiotic supplementation had a highly significant effect on cognitive function in people with cognitive impairment or Alzheimer's disease. For people without cognitive impairment, probiotic supplementation may be ineffective" - See probiotic supplements at Amazon.com.

Some sent me this:

Celastrol Modulates Multiple Signaling Pathways to Inhibit Proliferation of Pancreatic Cancer via DDIT3 and ATF3 Up-Regulation and RRM2 and MCM4 Down-Regulation - Onco Targets Ther. 2021 - "Celastrol, a quinone methide triterpenoid, is a natural product extracted from Tripterygium wilfordii Hook F. (“Thunder of God Vine”) plant and is used widely in TCM (traditional Chinese medications). The biological activities of celastrol have been extensively explored; it has been documented that celastrol has anticancer activity against various tumors, including leukemia, melanoma glioma, and prostate cancer.19–28 The celastrol anticancer activity was owed to its capability to compromise different cellular mechanisms in cancer cells. Celastrol is found to suppress tumor necrotic factor (TNF) induced cancer cells metastasis, nuclear factor (NF)-kB signaling, heat shock protein (HSP) 90, extracellular signal-regulated kinase (ERK), proteasome, and modulates TRAIL-induced apoptosis ... Celastrol inhibited pancreatic cancer proliferation through affecting several signaling pathways. The celastrol’s inhibitory effects on pancreatic cancer was basically attributed to DDIT3 and ATF3 activation and suppression of RRM2 and MCM4 genes" - See Thunder of God Vine at Amazon.com. Watch out for the side effects. I took it five times and every time I got a fever of about 102 about an hour after taking it and it lasted for seven hours. The first time I thought it was because I started doing my treadmill again. It's not going to work for me but that might not be the case for everyone.

  • Thunder God Vine: A Powerful Discovery for Pancreatic Cancer Patients - National Foundation for Cancer Research, 11/10/21 - "The key ingredient of the thunder god vine is called triptolide. Triptolide makes up a molecule called Minnelide, which appears to attack pancreatic cancer cells. It also attacks the tumor’s stroma or outer layer that shields it from the body’s immune system"

Neat Tech Stuff / "How To's":

I've tried many coffee machines. This one has the best taste.


Health Focus (Heart Disease):