2019 A comparison of gender-linked population cancer risks between alcohol and tobacco: how many cigarettes are there in a bottle of wine?

«In contrast to our knowledge about the number of cancers attributed to smoking, the number of cancers attributed to alcohol is poorly understood by the public. We estimate the increase in absolute risk of cancer (number of cases per 1000) attributed to moderate levels of alcohol, and compare these to the absolute risk of cancer attributed to low levels of smoking, creating a ‘cigarette-equivalent of population cancer harm’. Alcohol and tobacco attributable fractions were subtracted from lifetime general population risks of developing alcohol- and smoking-related cancers, to estimate the lifetime cancer risk in alcohol-abstaining non-smokers. This was multiplied by the relative risk of drinking ten units of alcohol or smoking ten cigarettes per week, and increasing levels of consumption. One bottle of wine per week is associated with an increased absolute lifetime cancer risk for non-smokers of 1.0% (men) and 1.4% (women). The overall absolute increase in cancer risk for one bottle of wine per week equals that of five (men) or ten cigarettes per week (women). Gender differences result from levels of moderate drinking leading to a 0.8% absolute risk of breast cancer in female non-smokers. One bottle of wine per week is associated with an increased absolute lifetime risk of alcohol-related cancers in women, driven by breast cancer, equivalent to the increased absolute cancer risk associated with ten cigarettes per week. These findings can help communicate that moderate levels of drinking are an important public health risk for women. The risks for men, equivalent to five cigarettes per week, are also of note.»

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2017 Cardiorespiratory fitness and death from cancer: a 42-year follow-up from the Copenhagen Male Study

«Objectives Poor cardiorespiratory fitness (CRF) is associated with death from cancer. If follow-up time is short, this association may be confounded by subclinical disease already present at the time of CRF assessment. This study investigates the association between CRF and death from cancer and any cause with 42 years and 44 years of follow-up, respectively.»

2018 Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing

«This study assesses the association between cardiorespiratory fitness and long-term mortality in adults undergoing exercise treadmill testing.»

New study calculates alcohol cancer risk in cigarette equivalents to help communicate risk

«The authors estimate that in non-smoking men, the absolute lifetime risk of cancer—that is, the risk of developing cancer during one's lifetime—associated with drinking one bottle of wine per week is 1.0%. For women, it is 1.4%. Thus, if 1,000 men and 1,000 women each drank one bottle of wine per week, around ten extra men and 14 extra women may develop cancer at some point in their life. In men, this risk appears to be associated primarily with cancers of the gastrointestinal tract, whereas in women, 55% of cases appear to be associated with breast cancer.»

«The authors also found that drinking three bottles of wine per week (approximately half a bottle per day) - a level known to increase the risks of a wide range of different health problems—was associated with an increase of absolute lifetime cancer risk to 1.9% in men and 3.6% in women, or 19 in 1,000 men and 36 in 1,000 women, respectively. This is equivalent to smoking roughly eight cigarettes per week for men and 23 cigarettes per week for women.»

How to Slow Brain Aging by Two Years | NutritionFacts.org

«The consumption of blueberries and strawberries is associated with delayed cognitive aging by as much as 2.5 years—thought to be because of brain-localizing anthocyanin phytonutrients, as shown on functional MRI scans.»

2019 Glycine supplementation extends lifespan of male and female mice

«Diets low in methionine extend lifespan of rodents, though through unknown mechanisms. Glycine can mitigate methionine toxicity, and a small prior study has suggested that supplemental glycine could extend lifespan of Fischer 344 rats. We therefore evaluated the effects of an 8% glycine diet on lifespan and pathology of genetically heterogeneous mice in the context of the Interventions Testing Program. Elevated glycine led to a small (4%–6%) but statistically significant lifespan increase, as well as an increase in maximum lifespan, in both males (p = 0.002) and females (p < 0.001). Pooling across sex, glycine increased lifespan at each of the three independent sites, with significance at p = 0.01, 0.053, and 0.03, respectively. Glycine‐supplemented females were lighter than controls, but there was no effect on weight in males. End‐of‐life necropsies suggested that glycine‐treated mice were less likely than controls to die of pulmonary adenocarcinoma (p = 0.03). Of the 40 varieties of incidental pathology evaluated in these mice, none were increased to a significant degree by the glycine‐supplemented diet. In parallel analyses of the same cohort, we found no benefits from TM5441 (an inhibitor of PAI‐1, the primary inhibitor of tissue and urokinase plasminogen activators), inulin (a source of soluble fiber), or aspirin at either of two doses. Our glycine results strengthen the idea that modulation of dietary amino acid levels can increase healthy lifespan in mice, and provide a foundation for further investigation of dietary effects on aging and late‐life diseases.»

«Hutchinson‐Gilford Progeria Syndrome (HGPS) is a devastating premature aging disease. Mouse models have been instrumental for understanding HGPS mechanisms and for testing therapies, which to date have had only marginal benefits in mice and patients. Barriers to developing effective therapies include the unknown etiology of progeria mice early death, seemingly unrelated to the reported atherosclerosis contributing to HGPS patient mortality, and mice not recapitulating the severity of human disease. Here, we show that progeria mice die from starvation and cachexia. Switching progeria mice approaching death from regular diet to high‐fat diet (HFD) rescues early lethality and ameliorates morbidity. Critically, feeding the mice only HFD delays aging and nearly doubles lifespan, which is the greatest lifespan extension recorded in progeria mice. The extended lifespan allows for progeria mice to develop degenerative aging pathologies of a severity that emulates the human disease. We propose that starvation and cachexia greatly influence progeria phenotypes and that nutritional/nutraceutical strategies might help modulate disease progression. Importantly, progeria mice on HFD provide a more clinically relevant animal model to study mechanisms of HGPS pathology and to test therapies.»

2011 Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats | The FASEB Journal

«Dietary methionine (Met) restriction (MR) extends lifespan in rodents by 30–40% and inhibits growth. Since glycine is the vehicle for hepatic clearance of excess Met via glycine N-methyltransferase (GNMT), we hypothesized that dietary glycine supplementation (GS) might produce biochemical and endocrine changes similar to MR and also extend lifespan. Seven-week-old male Fisher 344 rats were fed diets containing 0.43% Met/2.3% glycine (control fed; CF) or 0.43% Met/4%, 8% or 12% glycine until natural death. In 8% or 12% GS rats, median lifespan increased from 88 weeks (w) to 113 w, and maximum lifespan increased from 91 w to 119 w v CF. Body growth reduction was less dramatic, and not even significant in the 8% GS group. Dose-dependent reductions in several serum markers were also observed. Long-term (50 w) 12% GS resulted in reductions in mean (±SD) fasting glucose (158 ± 13 v 179 ± 46 mg/dL), insulin (0.7 ± 0.4 v 0.8 ± 0.3 ng/mL), IGF-1 (1082 ± 128 v 1407 ± 142 ng/mL) and triglyceride (113 ± 31 v 221 ± 56 mg/dL) levels compared to CF. Adiponectin, which increases with MR, did not change in GS after 12 w on diet. We propose that more efficient Met clearance via GNMT with GS could be reducing chronic Met toxicity due to rogue methylations from chronic excess methylation capacity or oxidative stress from generation of toxic by-products such as formaldehyde. This project received no outside funding.»

2007 Involvement of PI3K/PKG/ERK1/2 signaling pathways in cortical neurons to trigger protection by co-treatment of acetyl-L-carnitine and α-lipoic acid against HNE-mediated oxidative stress and neurotoxicity: Implications for Alzheimer's disease.

«Protein carbonyls are elevated in vulnerable regions of AD brain (40-42). Accumulation of HNE (7,8) and elevated 3-NT (43,44) in AD brain has also been reported. In the present study, a concentration-dependent study (with various combinations of ALCAR and LA) was carried out (Table 1) in the cortical neurons. A 29% significant increase in carbonyl (p <0.02) or HNE (p < 0.05) or 3-NT (p < 0.05) levels, respectively, was observed in neurons following 24 h of treatment with 10 μM HNE (Table 1). Pretreatment of neurons with ALCAR and LA at different combinations of concentration was shown to partially inhibit HNE-mediated protein oxidation and lipid-peroxidation. However, with ALCAR (75 μM) +LA (50 μM), there was a maximum significant decrease in the protein oxidation (p < 0.005) (Table 1) and lipid-peroxidation (p < 0.005) (Table 1). Pretreatment of cells with ZnPP IX or quercitin independently followed by ALCAR (75 μM) +LA (50 μM) and then 10 μM HNE produced less protection against HNE-induced protein carbonyl, HNE and 3-nitrotyrosine formation, compared to control than the protection produced by pretreatment of ALCAR (75 μM) +LA (50 μM) (p < 0.05) [data not shown]. In the presence of L-NMMA, there was less protection against HNE-induced 3-NT formation and a comparatively smaller effect on protein carbonyls or HNE formation [data not shown].»

2008 Interactions of the advanced glycation end product inhibitor pyridoxamine and the antioxidant α-lipoic acid on insulin resistance in the obese Zucker rat

«The average initial body weight did not differ among the various obese Zucker groups, and the average final body weight of the obese groups treated individually with PM (OP group) or R-ALA (OR group) were also not different compared with those of the obese vehicle-treated group (OV) (Fig. 1A). However, the average final body weight of the obese animals treated with the combination of PM and R-ALA (OPR group) was approximately 38 g or 9% less (P < .05) compared with that of the OV group. Both the initial and final body weight of the vehicle-treated lean Zucker rats (LV group) were significantly less (P < .05) compared with those of the OV group.»

2010 Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet

"Modern diets are largely heat-processed and as a result contain high levels of advanced glycation end products (AGEs). Dietary advanced glycation end products (dAGEs) are known to contribute to increased oxidant stress and inflammation, which are linked ..."

2016 Methionine restriction and lifespan control

«Dietary restriction (DR) without malnutrition is associated with longevity in various organisms. However, it has also been shown that reduced calorie intake is often ineffective in extending lifespan. Selecting optimal dietary regimens for DR studies is complicated, as the same regimen may lead to different outcomes depending on genotype and environmental factors. Recent studies suggested that interventions such as moderate protein restriction with/without adequate nutrition (e.g. particular amino acids or carbohydrates) may have additional beneficial effects mediated by certain metabolic and hormonal factors implicated in the biology of aging, regardless of total calorie intake. In particular, it was shown that restriction of a single amino acid, methionine, can mimic the effects of DR and extend lifespan in various model organisms. We discuss beneficial effects of methionine-restricted (MR) diet, the molecular pathways involved, and the use of this regimen in longevity interventions.»

2017 Spermidine prolongs lifespan and prevents liver fibrosis and hepatocellular carcinoma by activating MAP1S-mediated autophagy

«Liver fibrosis and hepatocellular carcinoma (HCC) have worldwide impact but continue to lack safe, low cost and effective treatments. In this study, we show how the simple polyamine spermidine can relieve cancer cell defects in autophagy which trigger oxidative stress-induced cell death and promote liver fibrosis and HCC. We found that the autophagic marker protein LC3 interacted with the microtubule-associated protein MAP1S which positively regulated autophagy flux in cells. MAP1S stability was regulated in turn by its interaction with the histone deacetylase HDAC4. Notably, MAP1S-deficient mice exhibited a 20% reduction in median survival and developed severe liver fibrosis and HCC under stress. Wild-type mice or cells treated with spermidine exhibited a relative increase in MAP1S stability and autophagy signaling via depletion of cytosolic HDAC4. Extending recent evidence that orally administered spermidine can extend lifespan in mice, we determined that life extension of up to 25% can be produced by lifelong administration which also reduced liver fibrosis and HCC foci as induced by chemical insults. Genetic investigations established that these observed impacts of oral spermidine administration relied upon MAP1S-mediated autophagy. Our findings offer a preclinical proof of concept for the administration of oral spermidine to prevent liver fibrosis and HCC and potentially extend lifespan.»

2017 One-carbon metabolism in cancer

«Cells require one-carbon units for nucleotide synthesis, methylation and reductive metabolism, and these pathways support the high proliferative rate of cancer cells. As such, anti-folate, drugs that target one-carbon metabolism, have long been used in the treatment of cancer. Amino acids, such as serine are a major one-carbon source, and cancer cells are particularly susceptible to deprivation of one-carbon units by serine restriction or inhibition of de novo serine synthesis. Recent work has also begun to decipher the specific pathways and sub-cellular compartments that are important for one-carbon metabolism in cancer cells. In this review we summarise the historical understanding of one-carbon metabolism in cancer, describe the recent findings regarding the generation and usage of one-carbon units and explore possible future therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism.»

2018 Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health

. Furthermore, the ketone β-hydroxybutyrate (BHB), which is elevated during nutritional ketosis to levels no greater than those resulting from fasting, acts as a signaling molecule in addition to its traditionally known role as an energy substrate. BHB signaling induces adaptations similar to mitohormesis, thereby expanding the potential benefit of nutritional ketosis beyond carbohydrate restriction. This review describes the evidence supporting enhancement of mitochondrial function and endogenous antioxidant defense in response to nutritional ketosis, as well as the potential mechanisms leading to these adaptations.

2018 Association between exposure to ambient air pollution and renal function in Korean adults

«We identified significant inverse relationships between the air pollutants PM₁₀ and NO₂ and eGFR in all statistical adjustment models (all p < 0.05). In the full covariate model, interquartile range increases in the annual mean concentration of PM₁₀ and NO₂ were associated with decreases in eGFR levels of 0.46 (95% CI = − 0.87, − 0.04) and 0.85 (95% CI = − 1.40, − 0.30), respectively. Three of the ambient air pollutants were significantly related to an increased risk of CKD in the unadjusted model (p < 0.0001), but all significant associations disappeared after adjusting for covariates (all p > 0.05).»

2018 Senolytics Improve Physical Function and Increase Lifespan in Old Age

«To test if senescent cells can directly cause physical dysfunction, we first transplanted senescent (SEN) or control, non-senescent (CON) preadipocytes (also termed adipocyte progenitors or adipose-derived stem cells²³) isolated from luciferase-expressing transgenic (LUC⁺) mice intraperitoneally into syngeneic, young (6-month-old) wild type (WT) animals (Fig. 1a). We induced cellular senescence using 10 Gray (Gy) radiation, which resulted in more than 85% of cells becoming senescent (Supplementary Fig. 1a,b). We transplanted preadipocytes because: 1) the SASP of radiation-induced senescent mouse preadipocytes (Supplementary Fig. 1c,d) resembles that of endogenous senescent cells with aging (Supplementary Fig. 1e)^20,24 and in idiopathic pulmonary fibrosis²⁵; 2) preadipocytes are less immunogenic or subject to rejection than other cell types²⁶; and 3) these cells are arguably the most abundant type of progenitors in humans²⁷ that are subject to cellular senescence. We also used doxorubicin to induce senescence to ascertain if the physiological impact of transplanted senescent cells is limited to the context of radiation-induced senescence: senescent cells induced by doxorubicin developed a SASP similar to that of radiation-induced senescent cells (Supplementary Fig. 1f). Five days after intraperitoneal transplantation of SEN or CON preadipocytes, the cells were mainly located in visceral fat (Fig. 1b,c and Supplementary Fig. 2a,b). Both the SEN and CON transplanted cells remained detectable by in vivo bioluminescence imaging (BLI) for up to 40 days (Supplementary Fig. 2c). Of note, we observed that senescent cells had higher luciferase activity than control non-senescent cells, even though they were from the same LUC transgenic mice (Supplementary Fig.2d).»

2018 Spermidine delays aging in humans

External supply of the natural polyamine spermidine can extend life span in model organisms including yeast, nematodes, flies and mice. Recent epidemiological evidence suggests that increased uptake of spermidine with food also reduces overall, cardiovascular and cancer-related mortality in humans.

2018 Are noise and air pollution related to the incidence of dementia? A cohort study in London, England

«2181 subjects (1.7%) received an incident diagnosis of dementia (39% mentioning Alzheimer’s disease, 29% vascular dementia). There was a positive exposure response relationship between dementia and all measures of air pollution except O₃, which was not readily explained by further adjustment. Adults living in areas with the highest fifth of NO₂ concentration (>41.5 µg/m³) versus the lowest fifth (<31.9 µg/m³) were at a higher risk of dementia (HR=1.40, 95% CI 1.12 to 1.74). Increases in dementia risk were also observed with PM_2.5, PM_2.5 specifically from primary traffic sources only and L_night, but only NO₂ and PM_2.5 remained statistically significant in multipollutant models. Associations were more consistent for Alzheimer’s disease than vascular dementia.»

2003 Restriction of dietary glycotoxins reduces excessive advanced glycation end products in renal failure patients.

"J Am Soc Nephrol. 2003 Mar;14(3):728-31. Clinical Trial; Randomized Controlled Trial; Research Support, U.S. Gov't, P.H.S."

2004 Advanced glycoxidation end products in commonly consumed foods.

"Foods of the fat group showed the highest amount of AGE content with a mean of 100+/-19 kU/g. High values were also observed for the meat and meat-substitute group, 43+/-7 kU/g. The carbohydrate group contained the lowest values of AGEs, 3.4+/-1.8 kU/g. The amount of AGEs present in all food categories was related to cooking temperature, length of cooking time, and presence of moisture. Broiling (225 degrees C) and frying (177 degrees C) resulted in the highest levels of AGEs, followed by roasting (177 degrees C) and boiling (100 degrees C)."

2004 AGEs activate mesangial TGF-beta-Smad signaling via an angiotensin II type I receptor interaction.

"AGEs increased intracellular ROS generation in mesangial cells, and this effect was significantly inhibited by an antiserum against RAGE. AGEs also were found to stimulate Ang II production in a time- and dose-dependent manner, which was completely prevented by an antioxidant, N-acetylcysteine (NAC). AGE-induced TGF-beta overproduction was completely blocked by candesartan, an Ang II type 1 receptor (AT1R) antagonist. Both candesartan and neutralizing antibody against TGF-beta completely prevented AGEs-induced Smad2 phosphorylation and TGF-beta-inducible promoter activity. Furthermore, AGEs were found to inhibit DNA synthesis and to stimulate de novo protein synthesis and fibronectin production in association with up-regulation of p27. All of these phenomena were completely prevented by candesartan or a polyclonal antibody against TGF-beta."

2007 Circulating glycotoxins and dietary advanced glycation endproducts: two links to inflammatory response, oxidative stress, and aging.

"Body weight, body mass index (BMI), and serum AGE, CML, and MG derivatives were higher in older participants, independent of gender. Serum CML correlated with levels of 8-isoprostanes (r = 0.448, p =.0001) as well as with Homeostasis Model Assessment index (HOMA), an index of insulin resistance (r = 0.247, p =.044). The consumption of dietary AGEs, but not of calories, correlated independently with circulating AGEs (CML: r = 0.415, p =.0001 and MG: r = 0.282, p =.002) as well as with high sensitivity C-reactive protein (hsCRP) (r = 0.200, p =.042)."

2007 Reduced oxidant stress and extended lifespan in mice exposed to a low glycotoxin diet: association with increased AGER1 expression.

2008 Oral glycotoxins determine the effects of calorie restriction on oxidant stress, age-related diseases, and lifespan.

2010 Total mortality risk in relation to use of less-common dietary supplements.

«A total of 3577 deaths occurred during 387,801 person-years of follow-up. None of the vitamin or mineral 10-y average intakes were associated with total mortality. Among the nonvitamin-nonmineral supplements, only glucosamine and chondroitin were associated with total mortality. The hazard ratio (HR) when persons with a high intake of supplements (> or =4 d/wk for > or =3 y) were compared with nonusers was 0.83 (95% CI: 0.72, 0.97; P for trend = 0.009) for glucosamine and 0.83 (95% CI: 0.69, 1.00; P for trend = 0.011) for chondroitin. There was also a suggestion of a decreased risk of total mortality associated with a high intake of fish-oil supplements (HR: 0.83; 95% CI: 0.70, 1.00), but the test for trend was not statistically significant.

For most of the supplements we examined, there was no association with total mortality. Use of glucosamine and use of chondroitin were each associated with decreased total mortality.»

2012 Dietary intakes of berries and flavonoids in relation to cognitive decline.

«Greater intakes of blueberries and strawberries were associated with slower rates of cognitive decline (eg, for a global score averaging all 6 cognitive tests, for blueberries: p-trend = 0.014 and mean difference = 0.04, 95% confidence interval [CI] = 0.01-0.07, comparing extreme categories of intake; for strawberries: p-trend = 0.022 and mean difference = 0.03, 95% CI = 0.00-0.06, comparing extreme categories of intake), after adjusting for multiple potential confounders. These effect estimates were equivalent to those we found for approximately 1.5 to 2.5 years of age in our cohort, indicating that berry intake appears to delay cognitive aging by up to 2.5 years. Additionally, in further supporting evidence, greater intakes of anthocyanidins and total flavonoids were associated with slower rates of cognitive decline (p-trends = 0.015 and 0.053, respectively, for the global score).»

2012 Effect of alpha-lipoic acid on memory, oxidation, and lifespan in SAMP8 mice.

«Oxidative damage is associated with neurodegenerative disorders such as Alzheimer's disease (AD). The antioxidant alpha-lipoic acid has been found to improve memory in mouse models of AD. Here, we administered alpha-lipoic acid daily to SAMP8 mice starting at 11 months of age and continuing until death. We found that treatment with alpha-lipoic acid decreased survival from 34 weeks in those receiving vehicle to 20 weeks. A subset of 18 month old mice given alpha-lipoic acid for two weeks and then tested in an object-place recognition paradigm had improved memory. A second subset of 18 month old mice given alpha-lipoic acid for two weeks and tested in the Barnes maze had improved learning. After testing, the mice were sacrificed and indices of oxidative damage were measured in the brain tissue. The mice that received alpha-lipoic acid had significantly increased glutathione and decreased glutathione peroxidase and malondialdehyde indicating reversal of oxidative stress. These results indicate that alpha-lipoic acid improves memory and reverses indices of oxidative stress in extremely old SAMP8 mice, but decreases lifespan. These findings are similar to studies using other types of antioxidant.»

2012 Blueberries and neuronal aging.

«As the population of people in the United States over the age of 65 years continues to increase, so too will the incidence of age-related pathologies, including decreases in cognitive and motor function. In cases of severe deficits in memory or motor function, hospitalization and/or custodial care would be a likely outcome. This means that unless some way is found to reduce these age-related decrements in neuronal function, health care costs will continue to rise exponentially. Evidence is accumulating that consumption of blueberries may be one strategy to forestall or even reverse age-related neuronal deficits, as well as their subsequent behavioral manifestations, in order to increase healthy aging. Research suggests that the polyphenolic compounds found in blueberries exert their beneficial effects either through their ability to lower oxidative stress and inflammation or directly by altering the signaling involved in neuronal communication. These interventions, in turn, may protect against age-related deficits in cognitive and motor function. Appropriately, the US Department of Agriculture has figured prominently in these discoveries, through the efforts of two USDA researchers who worked for the department 100 years apart.»

2013 Diet-derived advanced glycation end products or lipofuscin disrupts proteostasis and reduces life span in Drosophila melanogaster.

2014 Serine and glycine metabolism in cancer.

«Serine and glycine are biosynthetically linked, and together provide the essential precursors for the synthesis of proteins, nucleic acids, and lipids that are crucial to cancer cell growth. Moreover, serine/glycine biosynthesis also affects cellular antioxidative capacity, thus supporting tumour homeostasis. A crucial contribution of serine/glycine to cellular metabolism is through the glycine cleavage system, which refuels one-carbon metabolism; a complex cyclic metabolic network based on chemical reactions of folate compounds. The importance of serine/glycine metabolism is further highlighted by genetic and functional evidence indicating that hyperactivation of the serine/glycine biosynthetic pathway drives oncogenesis. Recent developments in our understanding of these pathways provide novel translational opportunities for drug development, dietary intervention, and biomarker identification of human cancers.»

2014 A study of air pollutants influencing life expectancy and longevity from spatial perspective in China.

«Life expectancy and longevity are influenced by air pollutants and socioeconomic status, but the extend and significance are still unclear. Better understanding how the spatial differences of life expectancy and longevity are affected by air pollutants is needed for generating public health and environmental strategies since the whole of China is now threatened by deteriorated air quality. 85 major city regions were chosen as research areas. Geographically Weight Regression (GWR) and Stepwise Regression (SR) were used to find the spatial correlations between health indicators and air pollutants, adjusted by per capita GDP(1). The results were, regions with higher life expectancy were mainly located in the east area and areas with good air quality, a regional difference of 10 μg/m(3) in ambient air SO2(2) could cause adjusted 0.28 year's difference in life expectancy, a regional difference of 10 μg/m(3) in ambient air PM10(3) could lead to a longevity ratio difference of 2.23, and per capita GDP was positively associating with life expectancy but not longevity ratio, with a regional difference of 10,000 RMB(4) associating with adjusted 0.49 year's difference in life expectancy. This research also showed the evidences that there exist spatially differences for ambient air PM10 and SO2 influencing life expectancy and longevity in China, and this influences were clearer in south China.»

2014 D-beta-hydroxybutyrate extends lifespan in C. elegans.

Upregulation of antioxidant defense by BHB-induced HDAC inhibition also appears to be the mechanism through which exogenous BHB extends lifespan in C. elegans

2015 Age and amyloid effects on human central nervous system amyloid-beta kinetics.

Age is the single greatest risk factor for Alzheimer's disease (AD), with the incidence doubling every 5 years after age 65.

We found a highly significant correlation between increasing age and slowed Aβ turnover rates (2.5-fold longer half-life over five decades of age). In addition, we found independent effects on Aβ42 kinetics specifically in participants with amyloid deposition. Amyloidosis was associated with a higher (>50%) irreversible loss of soluble Aβ42 and a 10-fold higher Aβ42 reversible exchange rate.

2015 Bicarbonate-sensitive calcification and lifespan of klotho-deficient mice.

«Klotho, a protein counteracting aging, is a powerful inhibitor of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] formation and regulator of mineral metabolism. In klotho hypomorphic (kl/kl) mice, excessive 1,25(OH)2D3 formation lead to hypercalcemia, hyperphosphatemia and vascular calcification, severe growth deficits, accelerated aging and early death. Kl/kl mice further suffer from extracellular volume depletion and hypotension, leading to the stimulation of antidiuretic hormone and aldosterone release. A vitamin D-deficient diet, restriction of dietary phosphate, inhibition of mineralocorticoid receptors with spironolactone, and dietary NaCl all extend the lifespan of kl/kl mice. Kl/kl mice suffer from acidosis. The present study explored whether replacement of tap drinking water by 150 mM NaHCO3 affects the growth, tissue calcification, and lifespan of kl/kl mice. As a result, NaHCO3 administration to kl/kl mice did not reverse the growth deficit but substantially decreased tissue calcification and significantly increased the average lifespan from 78 to 127 days. NaHCO3 did not significantly affect plasma concentration of 1,25(OH)2D3 and Ca(2+) but significantly decreased plasma phosphate concentration and plasma aldosterone concentration. The present study reveals a novel effect of bicarbonate, i.e., a favorable influence on vascular calcification and early death of klotho-deficient mice.»

2016 NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice.

«Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD(+) precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmd(mdx)/J) mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span. Strategies that conserve cellular NAD(+) may reprogram dysfunctional SCs and improve life span in mammals.»

2016 Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance.

«Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS-induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed.»

2016 Cardioprotection and lifespan extension by the natural polyamine spermidine.

«Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease.»

2017 Dietary spermidine for lowering high blood pressure.

«Loss of cardiac macroautophagy/autophagy impairs heart function, and evidence accumulates that an increased autophagic flux may protect against cardiovascular disease. We therefore tested the protective capacity of the natural autophagy inducer spermidine in animal models of aging and hypertension, which both represent major risk factors for the development of cardiovascular disease. Dietary spermidine elicits cardioprotective effects in aged mice through enhancing cardiac autophagy and mitophagy. In salt-sensitive rats, spermidine supplementation also delays the development of hypertensive heart disease, coinciding with reduced arterial blood pressure. The high blood pressure-lowering effect likely results from improved global arginine bioavailability and protection from hypertension-associated renal damage. The polyamine spermidine is naturally present in human diets, though to a varying amount depending on food type and preparation. In humans, high dietary spermidine intake correlates with reduced blood pressure and decreased risk of cardiovascular disease and related death. Altogether, spermidine represents a cardio- and vascular-protective autophagy inducer that can be readily integrated in common diets.»

2018 Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies.

In comparison to those who reported drinking >0-≤100 g per week, those who reported drinking >100-≤200 g per week, >200-≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively.

2018 Higher spermidine intake is linked to lower mortality: a prospective population-based study.

«All-cause mortality (deaths per 1000 person-years) decreased across thirds of increasing spermidine intake from 40.5 (95% CI: 36.1, 44.7) to 23.7 (95% CI: 20.0, 27.0) and 15.1 (95% CI: 12.6, 17.8), corresponding to an age-, sex- and caloric intake-adjusted 20-y cumulative mortality incidence of 0.48 (95% CI: 0.45, 0.51), 0.41 (95% CI: 0.38, 0.45), and 0.38 (95% CI: 0.34, 0.41), respectively. The age-, sex- and caloric ratio-adjusted HR for all-cause death per 1-SD higher spermidine intake was 0.74 (95% CI: 0.66, 0.83; P < 0.001). Further adjustment for lifestyle factors, established predictors of mortality, and other dietary features yielded an HR of 0.76 (95% CI: 0.67, 0.86; P < 0.001). The association was consistent in subgroups, robust against unmeasured confounding, and independently validated in the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) Study (age-, sex-, and caloric ratio-adjusted HR per 1-SD higher spermidine intake: 0.71; 95% CI: 0.53, 0.95; P = 0.019). The difference in mortality risk between the top and bottom third of spermidine intakes was similar to that associated with a 5.7-y (95% CI: 3.6, 8.1 y) younger age.»

2018 Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

«Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2·2% (95% uncertainty interval [UI] 1·5-3·0) of age-standardised female deaths and 6·8% (5·8-8·0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3·8% (95% UI 3·2-4·3) of female deaths and 12·2% (10·8-13·6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2·3% (95% UI 2·0-2·6) and male attributable DALYs were 8·9% (7·8-9·9). The three leading causes of attributable deaths in this age group were tuberculosis (1·4% [95% UI 1·0-1·7] of total deaths), road injuries (1·2% [0·7-1·9]), and self-harm (1·1% [0·6-1·5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27·1% (95% UI 21·2-33·3) of total alcohol-attributable female deaths and 18·9% (15·3-22·6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0·0-0·8) standard drinks per week.

INTERPRETATION:
Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.»

2019 Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion.

«The deregulation of metabolism is a hallmark of aging. As such, changes in the expression of metabolic genes and the profiles of amino acid levels are features associated with aging animals. We previously reported that the levels of most amino acids decline with age in Caenorhabditis elegans (C. elegans). Glycine, in contrast, substantially accumulates in aging C. elegans. In this study we show that this is coupled to a decrease in gene expression of enzymes important for glycine catabolism. We further show that supplementation of glycine significantly prolongs C. elegans lifespan, and early adulthood is important for its salutary effects. Moreover, supplementation of glycine ameliorates specific transcriptional changes that are associated with aging. Glycine feeds into the methionine cycle. We find that mutations in components of this cycle, methionine synthase (metr-1) and S-adenosylmethionine synthetase (sams-1), completely abrogate glycine-induced lifespan extension. Strikingly, the beneficial effects of glycine supplementation are conserved when we supplement with serine, which also feeds into the methionine cycle. RNA-sequencing reveals a similar transcriptional landscape in serine- and glycine-supplemented worms both demarked by widespread gene repression. Taken together, these data uncover a novel role of glycine in the deceleration of aging through its function in the methionine cycle.»

1999 Leaky gut in alcoholic cirrhosis: a possible mechanism for alcohol-induced liver damage.

«Alcoholics with no liver disease showed a small but significant increase in sucrose excretion. Alcoholics with chronic liver disease demonstrated a marked and highly significant increase in urinary sucrose excretion relative to the controls, to the alcoholics with no liver disease, and to the nonalcoholics with liver disease. Alcoholics with chronic liver disease demonstrated a marked and highly significant increase in both lactulose absorption and in the urinary lactulose/mannitol ratio (alcoholics 0.703 vs controls 0.019, p = 0.01). In contrast, alcoholics with no liver disease and nonalcoholics with liver disease showed normal lactulose absorption and normal lactulose/mannitol ratio.»

1999 Dietary glycine inhibits the growth of B16 melanoma tumors in mice.

«Dietary glycine inhibited hepatocyte proliferation in response to the carcinogen WY-14,643. Since increased cell replication is associated with hepatic cancer caused by WY-14,643, glycine may have anti-cancer properties. Therefore, these experiments were designed to test the hypothesis that dietary glycine would inhibit the growth of tumors arising from B16 melanoma cells implanted subcutaneously in mice. C57BL/6 mice were fed diet supplemented with 5% glycine and 15% casein or control diet (20% casein) for 3 days prior to subcutaneous implantation of B16 tumor cells. Tumor volume was estimated from tumor diameter for 14 days. Tumors were excised, weighed and sectioned for histology post-mortem. B16 cells and endothelial cells were cultured in vitro to assess effects of glycine on cell growth. Statistical tests were two-sided and a P-value of 0.05 was defined as a significant difference between groups. Weight gain did not differ between mice fed control and glycine-containing diets. B16 tumors grew rapidly in mice fed control diet; however, in mice fed glycine diet, tumor size was 50-75% less. At the time of death, tumors from glycine-fed mice weighed nearly 65% less than tumors from mice fed control diet (P < 0.05). Glycine (0.01-10 mM) did not effect growth rates of B16 cells in vitro. Moreover, tumor volume and mitotic index of B16 tumors in vivo did not differ 2 days after implantation when tumors were small enough to be independent of vascularization. After 14 days, tumors from mice fed dietary glycine had 70% fewer arteries (P < 0.05). Furthermore, glycine (0.01-10 mM) inhibited the growth of endothelial cells in vitro in a dose-dependent manner (P < 0.05; IC50 = 0.05 mM). These data support the hypothesis that dietary glycine prevents tumor growth in vivo by inhibiting angiogenesis through mechanisms involving inhibition of endothelial cell proliferation.»