Chemobrain: An accelerated aging process linking adenosine A2A receptor signaling in cancer survivors.

Chemotherapy has a significant positive impact in cancer treatment outcomes, reducing recurrence and mortality. However, many cancer surviving children and adults suffer from aberrant chemotherapy neurotoxic effects on learning, memory, attention, executive functioning, and processing speed. This chemotherapy-induced cognitive impairment (CICI) is referred to as "chemobrain" or "chemofog". While the underlying mechanisms mediating CICI are still unclear, there is strong evidence that chemotherapy accelerates the biological aging process, manifesting as effects which include telomere shortening, epigenetic dysregulation, oxidative stress, mitochondrial defects, impaired neurogenesis, and neuroinflammation, all of which are known to contribute to increased anxiety and neurocognitive decline. Despite the increased prevalence of CICI, there exists a lack of mechanistic understanding by which chemotherapy detrimentally affects cognition in cancer survivors. Moreover, there are no approved therapeutic interventions for this condition. To address this gap in knowledge, this review attempts to identify how adenosine signaling, particularly through the adenosine A2A receptor, can be an essential tool to attenuate accelerated aging phenotypes. Importantly, the adenosine A2A receptor uniquely stands at the crossroads of cancer treatment and improved cognition, given that it is widely known to control tumor induced immunosuppression in the tumor microenvironment, while also posited to be an essential regulator of cognition in neurodegenerative disease. Consequently, we propose that the adenosine A2A receptor may provide a multifaceted therapeutic strategy to enhance anticancer activity, while combating chemotherapy induced cognitive deficits, both which are essential to provide novel therapeutic interventions against accelerated aging in cancer survivors.

Aflatoxin B1 exposure triggers inflammation and premature skin aging via ERMCS/Ca2+/ROS signaling cascade.

Aflatoxin B1 (AFB1) is a recognized hazard environmental contaminant mainly found in cereal and fruits. The toxicity of AFB1 exposure to various organs has been revealed in some literature. In current study, we explored the effect of AFB1 exposure on premature aging/senescence of skin. In vivo, 8-week-old C57 mice were used as models to evaluate the effect of dietary AFB1 exposure on premature skin aging. The results showed that AFB1 exposure caused premature skin aging by testing aging markers. Additionally, AFB1 led to oxidative stress and inflammatory response. In vitro, AFB1 exposure triggered premature cellular senescence in mouse skin fibroblasts cells (L929 cells) by assessing a range of cellular senescence-related markers. Further, the potential molecular mechanism by which AFB1 induce the premature skin aging was studied. ROS and Ca2+ is proven to be the key molecules in AFB1-induced cellular senescence. Further, through eliminating Ca2+, AFB1-caused oxidative stress and cellular senescence were both attenuated, suggesting that Ca2+ overload in the mitochondria results in cellular senescence by increasing ROS production. Next, we analyzed the causes of Ca2+ overload, and results showed that AFB1 exposure induces Ca2+ overload through increasing the formation of mitoguardin (Miga) and vesicle-associated membrane protein (VAMP)-associated protein (Vap33)-mediated endoplasmic reticulum (ER)-mitochondria contact sites (ERMCS). AFB1 exposure also inhibited mitophagy, leading to accelerate L929 cell senescence. In short, combining in vivo and in vitro results, we demonstrate that exposure to AFB1 causes premature skin aging, which is dependent on ERMCS/Ca2+/ROS/ signaling axis. The current study suggests that prolonged exposure to AFB1 makes skin more vulnerable to damage.

Antiaging Effects of Vicatia thibetica de Boiss Root Extract on Caenorhabditis elegans and Doxorubicin-Induced Premature Aging in Adult Mice.

The roots of Vicatia thibetica de Boiss are a kind of Chinese herb with homology of medicine and food. This is the first report showing the property of the extract of Vicatia thibetica de Boiss roots (HLB01) to extend the lifespan as well as promote the healthy parameters in Caenorhabditis elegans (C. elegans). For doxorubicin- (Doxo-) induced premature aging in adult mice, HLB01 counteracted the senescence-associated biomarkers, including P21 and γH2AX. Interestingly, HLB01 promoted the expression of collagen in C. elegans and mammalian cell systemically, which might be one of the essential factors to exert the antiaging effects. In addition, HLB01 was also found as a scavenger of free radicals, thereby performing the antioxidant ability. Lifespan extension by HLB01 was also dependent on DAF-16 and HSF-1 via oxidative stress resistance and heat stress resistance. Taken together, overall data suggested that HLB01 could extend the lifespan and healthspan of C. elegans and resist Doxo-induced senescence in mice via promoting the expression of collagen, antioxidant potential, and stress resistance.

Spectroscopic Signature of Red Blood Cells in a D-Galactose-Induced Accelerated Aging Model.

This work presents a semi-quantitative spectroscopic approach, including FTIR-ATR and Raman spectroscopies, for the biochemical analysis of red blood cells (RBCs) supported by the biochemical, morphological and rheological reference techniques. This multi-modal approach provided the description of the RBC alterations at the molecular level in a model of accelerated aging induced by administration of D-galactose (D-gal), in comparison to natural aging. Such an approach allowed to conclude that most age-related biochemical RBC membrane changes (a decrease in lipid unsaturation and the level of phospholipids, or an increase in acyl chain shortening) as well as alterations in the morphological parameters and RBC deformability are well reflected in the D-gal model of accelerated aging. Similarly, as in natural aging, a decrease in LDL level in blood plasma and no changes in the fraction of glucose, creatinine, total cholesterol, HDL, iron, or triglycerides were observed during the course of accelerated aging. Contrary to natural aging, the D-gal model led to an increase in cholesterol esters and the fraction of total esterified lipids in RBC membranes, and evoked significant changes in the secondary structure of the membrane proteins. Moreover, a significant decrease in the phosphorous level of blood plasma was specific for the D-gal model. On the other hand, natural aging induced stronger changes in the secondary structures of the proteins of the RBCs' interior. This work proves that research on the aging mechanism, especially in circulation-related diseases, should employ the D-gal model with caution. Nonetheless, the D-gal model enables to imitate age-related rheological alterations in RBCs, although they are partially derived from different changes observed in the RBC membrane at the molecular level.

Lung transcriptomic clock predicts premature aging in cigarette smoke-exposed mice.

BACKGROUND: Lung aging is characterized by a number of structural alterations including fibrosis, chronic inflammation and the alteration of inflammatory cell composition. Chronic exposure to cigarette smoke (CS) is known to induce similar alterations and may contribute to premature lung aging. Additionally, aging and CS exposure are associated with transcriptional alterations in the lung. The current work aims to explore the interaction between age- and CS- associated transcriptomic perturbations and develop a transcriptomic clock able to predict the biological age and the impact of external factors on lung aging. RESULTS: Our investigations revealed a substantial overlap between transcriptomic response to CS exposure and age-related transcriptomic alterations in the murine lung. Of particular interest is the strong upregulation of immunoglobulin genes with increased age and in response to CS exposure, indicating an important implication of B-cells in lung inflammation associated with aging and smoking. Furthermore, we used a machine learning approach based on Lasso regression to build a transcriptomic age model that can accurately predict chronological age in untreated mice and the deviations associated with certain exposures. Interestingly, CS-exposed-mice were predicted to be prematurely aged in contrast to mice exposed to fresh air or to heated tobacco products (HTPs). The accelerated aging rate associated with CS was reversed upon smoking cessation or switching to HTPs. Additionally, our model was able to predict premature aging associated with thoracic irradiation from an independent public dataset. CONCLUSIONS: Aging and CS exposure share common transcriptional alteration patterns in the murine lung. The massive upregulation of B-cell restricted genes during these processes shed light on the contribution of cell composition and particularly immune cells to the measured transcriptomic signal. Through machine learning approach, we show that gene expression changes can be used to accurately monitor the biological age and the modulations associated with certain exposures. Our findings also suggest that the premature lung aging is reversible upon the reduction of harmful exposures.

Indexes for flotation and circling, two non-search behaviors in the water maze, sensitive to d-galactose-induced accelerated aging and Alzheimer's disease.

The study of behavioral and psychological symptoms of dementia (BPSD) has been largely neglected in most experimental research on Alzheimer's disease (AD) classically focused on cognitive symptoms. The aquatic environment of the Morris water maze (MWM) implies a stressful condition for mice leading to cognitive performances with presence of other behaviors related to emotionality. This can be critical in models such as the 3xTg-AD mice that exhibit a noticeable BPSD-like profile. The present work is aimed to provide a quantitative (number of episodes and duration) and qualitative (prevalence) analysis of flotation and circling, the most common 'non-searching behaviors' elicited in the MWM. We studied the expression of these behaviors in 6-month-old gold-standard wildtype C57BL/6 mice (genetic background) and 3xTg-AD mice (onset of disease) and when both genotypes were submitted to chronic d-galactose induced accelerated aging. Elicitation of floating and circling was recorded during three standard MWM paradigms: visual perceptual learning, place task for spatial reference memory and a final probe trial for short-term memory. In view of the results, we demonstrate that the index of 'flotation', characteristic of non-transgenic performance, is sensitive (reduction) to accelerated aging and AD. Conversely, circling behavior, characteristic of 3xTg-AD mice, can be an additional tool for evaluating BPSD-like symptoms in AD-models while its index unveils bizarre behavior induced by d-galactose induced aging. These results can be useful in relation to preventive and/or therapeutical interventions targeting AD but they may also be suitable in the evaluation of the potential risk factors in animals with normal aging.

Gallic acid attenuates thymic involution in the d-galactose induced accelerated aging mice.

Senescence is an inevitable and complicated phenomenon. Age-associated thymic involution increases the risk of infectious diseases, which results in the immunosenescence and leads to a poor immune function. d-galactose (d-gal) can cause damages that resemble accelerated aging in mice. Gallic acid (GA), as one of the natural phenolic compounds, has been demonstrated to act in antioxidant and anti-tumor effects. In this study, we explored the effects of GA in preventing the age-related thymic involution and the alterations of the forkhead box protein N1 (FoxN1) in d-gal induced accelerated aging mice. The accelerated aging mice model was established by intraperitoneal injection d-gal for eight weeks and given GA with 200, 250, 500 mg/kg body weight per day, respectively, for six weeks. It showed that the d-gal-treated mice developed structural changes in the thymi compared to normal control mice. With supplement of GA, the mice restored the normal thymic anatomy, including the thickening cortex compartment and clearer cortico-medullary junction. The d-gal-treated mice showed a severe reduction in the number of thymocytes, GA mice also displayed the increased numbers of CD4 + T cells through flow cytometric analysis. GA treatment increased the proliferative cells by BrdU incorporation assay and reduced the numbers of apoptotic cells with FITC-12-dUTP labeling (TUNEL). The expression of FoxN1 was also found increased in GA treated mice by immunohistochemistry and quantitative reverse transcriptase PCR (qRT-PCR). Taken together, our results suggested that the administration of GA opposed the involution of thymus via stimulation of FoxN1 expression and proliferation of cells in a dose-dependent manner.

Lactobacilli modulated AMPK activity and prevented telomere shortening in ageing rats.

This study aimed to evaluate the anti-ageing effects of different strains of lactobacilli putative probiotics on an ageing rat model as induced by D-galactose and a high fat diet. Male Sprague-Dawley rats were fed with high fat diet (54% kcal fat) and injected with D-galactose daily for 12 weeks to induce ageing. The effects of putative probiotic strains on age-related impairment such as telomere length, plasma lipid peroxidation, hepatic 5'adenosine monophosphate-activated protein kinase (AMPK) expression, as well as endurance performance were evaluated. Administration of statin, Lactobacillus plantarum DR7 (LP-DR7), Lactobacillus fermentum DR9 (LF-DR9), and Lactobacillus reuteri 8513d (LR-8513d) significantly reduced the shortening of telomere and increased the expression of AMPK subunit-α1 (P<0.05). Plasma lipid peroxidation was lower (P<0.05) in groups administered with statin and LF-DR9 as compared to the control. AMPK subunit-α2 was elevated in rats administered with LP-DR7 as compared to the control (P<0.05). Using an in vivo ageing rat model, the current study has illustrated the potentials of lactobacilli putative probiotics in alleviation of age-related impairment in a strain-dependent manner.

Telomere shortening in alcohol dependence: Roles of alcohol and acetaldehyde.

Heavy drinking leads to premature aging and precipitates the onset of age-related diseases. Acetaldehyde (AcH), a toxic metabolite of ethanol, has been implicated in various types of cancer. However, whether alcohol accelerates biological aging at a cellular level is controversial and the mechanism involved is unclear. We addressed these questions by measuring telomere length (TL) in peripheral blood leukocytes of Japanese patients with alcohol dependence (AD) and examined the association between TL, genetic variants of alcohol dehydrogenase (ADH)1B and aldehyde dehydrogenase (ALDH)2, and other clinical characteristics. A total of 134 male AD patients and 121 age- and sex-matched healthy controls were evaluated. All patients received endoscopic screening for cancer of the upper aerodigestive tract (UADT). TL was almost 50% shorter in AD patients relative to controls. There were no significant differences in TL between AD patients with and without UADT cancer, and no associations between ADH1B and ALDH2 genotypes and TL. AD patients with thiamine (vitamin B1) deficiency at admission had significantly shorter TL than those with normal thiamine status. Although the exact mechanism underlying the shorter TL in AD patients remain unclear, our findings suggest that alcohol rather than AcH is associated with telomere shortening in AD, which may be accelerated by thiamine deficiency. Future studies should also focus on the association between telomere shortening and TD in the context of oxidative stress.

Protective effects of ginsenoside Rg1 on splenocytes and thymocytes in an aging rat model induced by d-galactose.

Physiological aging is associated with a range of medical problems. However, the treatment of aging-associated diseases and prolonging human life are vital to our current aging societies. Panax ginseng, a traditional Chinese medicine, has been shown to have anti-oxidative and anti-aging effects. In the current study, aging rats induced by d-galactose were administered ginsenoside Rg1, then splenocytes and thymocytes were extracted and changes in activity were detected. The results demonstrated that compared with the d-gal group, the level of advanced glycation end products (AGE), the ratio of splenocytes and thymocytes in G0 phase (%), and apoptosis (%) of splenocytes and thymocytes, the ratio (%) of SA-gal positive splenocytes and thymocytes, the content of reactive oxygen species (ROS) and malondialdehyde (MDA), the ratio of glutathione (GSH) to oxidized glutathione (GSSG) and senescence-associated protein expression were significantly decreased and the index of the spleen and thymus, the proportion of white pulp in the spleen, the proportion of cortex in the thymus, the content of interleukin-2 (IL-2), interleukin-6 (IL-6), granulocyte-macrophage colony stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α), the activities of superoxide dismutase (SOD), and the proliferative capacity of splenocytes and thymocytes were increased in the Rg1+ d-gal group. These findings demonstrated that ginsenoside Rg1 may antagonize spleen and thymus damage in d-galactose-induced aging rats by alleviating oxidative stress injury and down-regulating the expression of senescence-associated protein.

Sexual Dimorphism in the Behavioral Responses and the Immunoendocrine Status in d-Galactose-Induced Aging.

For almost 20 years, chronic systemic d-galactose, a monosaccharide abundantly present in milk products, fruits, and vegetables, has been used as a tool to achieve models of accelerated aging. Its neurotoxicity, induced by abnormal accumulation of reactive oxygen species and advanced glycation end products, has been widely reported. However, behavioral outcomes are still controversial and little is known about sex-dependent vulnerability. We performed a comprehensive behavioral and multifunctional screening of the chronic effects of low (50 mg/kg) and high (100 mg/kg) doses of d-galactose in 6-month-old male and female gold-standard C57BL/6 mice. Twelve classical tests with convergent validity analyzed sensorimotor, emotional and cognitive domains, indicating the existence of thresholds of response. Distinct vulnerability patterns were found in a selective sex- and dose-dependent manner. In males, d-galactose induced sensorimotor impairment and immunoendocrine senescence, but the low dose resulted in improved learning and memory. Oppositely, d-galactose-treated females exhibited a dose-dependent worse motor and spatial learning, but improved memory. Behavioral outcome items point at distinct neuronal substrates underlying the functional capacity of d-galactose-treated animals to meet task-dependent performance demands. They support that males and females can be regarded as two exceptional natural scenarios to study the functional interplay in the cross talk of homeostatic networks in aging.

[Interrelation of rates of a biological aging with neurophysiological features at patients with professional neurointoxications].

In the hospital conducted studying of functional activity of a brain of patients with professional neurointoxications for the purpose of detection of neurophysiological features of formation of the accelerated rates of biological aging at the working, being affected neurotoxicant is carried out. During the research it is shown that rates of aging at patients with professional neurointoxications on average in 85% of cases have premature character. The general signs of defeat of structures of a brain at professional intoxication are defined by mercury irrespective of a disease stage at the accelerated biological aging. For toxic impacts on a nervous system the characteristic, uniting sign distinguishing from the accelerated rates of aging of other etiology is the indicator characterizing augmentation of a latence of peak of P2 of the visual caused potentials. Based on the analysis of the received correlations it is set that in case of professional neurointoxications permanent disorganization of the functional activity of a brain in the form of cortical and subcortical violations of sensor regulatory systems of a brain is a consequence of chronic influence of vapors of metal mercury and a complex of toxic substances and the reason of the accelerated biological aging.

Prenatal Exposure to DEHP Induces Premature Reproductive Senescence in Male Mice.

Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used phthalate, and it is an endocrine-disrupting chemical. This study tested a hypothesis that prenatal exposure to DEHP lays the foundation for premature gonadal dysfunction and subsequent reproductive senescence in male mice. Pregnant female CD-1 mice were orally dosed with vehicle control (tocopherol-stripped corn oil) or with 20 µg/kg/day, 200 µg/kg/day, 500 mg/kg/day, or 750 mg/kg/day of DEHP from gestational day 11 to birth. Overall, the prenatal DEHP exposure did not cause any overt physical health problems in male offspring, as no significant differences in their body nor gonadal weight were seen up to the age of 23 months. However, an age- and dose-dependent gonadal dysfunction was observed. As early as 7 months of age, the 750 mg/kg/day group of mice exhibited significantly reduced fertility. At 19 months of age, 86% of the 750 mg/kg/day mice became infertile, whereas only 25% of the control mice were infertile. At this age, all of the DEHP-exposed mice had lower serum testosterone levels, higher serum estradiol levels, and higher LH levels compared with control mice. Histological evaluations showed that mice prenatally exposed to DEHP displayed a wide array of gonadal and epididymal abnormalities such as increased germ cell apoptosis, degenerative seminiferous tubules, oligozoospermia, asthenozoospermia, and teratozoospermia in comparison to age-matching control mice. In summary, this study shows that prenatal exposure to DEHP induces premature reproductive senescence in male mice.

Comparison of behavioral and biochemical deficits in rats with hereditary defined or D-galactose-induced accelerated senescence: evaluating the protective effects of diosgenin.

One of the important factors in aging is oxidative stress and aging-related disturbances are believed be ameliorated by antioxidants. Diosgenin is a bio-active ingredient of dioscorea that is widely used in Chinese medicine, shows anti-oxidant activity and improves some aging-related deficits in senescent and menopausal animals. We compared alterations in behavior, biochemical parameters (plasma levels of the uric acid, creatinine, calcium, phosphate, total cholesterol, low-density lipoprotein cholesterol and triglycerides, and the plasma activity of aminotransferases AST and ALT), and sperm motility in two models of accelerated senescence (d-galactose-induced (150 mg/kg/day, i.p., 57 days) aging in Wistar rats vs. genetically defined in OXYS rats) and examined the protective effects of diosgenin (10 or 50mg/kg/day, p.o., 57 days). Both models had augmented levels of ALT activity indicating hepatopathology. Compared to d-galactose-treated animals, OXYS rats demonstrated profound biochemical alterations (hypocalcemia, hypophosphatemia, and hypocholesterolemia) and behavioral deficits (impaired object recognition, decreased sexual motivation and locomotor activity, retarded learning) that confirmed the difference in the mechanisms of accelerated senescence in these models. We first showed diminished sperm motility in males of both models of accelerated senescence studied. Chronic diosgenin treatment failed to improve biochemical and behavioral disturbances and had some undesirable side effects on body weight and working memory in OXYS rats. However, diosgenin restored moderately decreased sperm motility in d-galactose-treated Wistar males and might be recommended for treatment of mild age-related reproductive dysfunctions.

Aging and HIV/AIDS: pathogenetic role of therapeutic side effects.

The intersection of aging and HIV/AIDS is a looming 'epidemic within an epidemic.' This paper reviews how HIV/AIDS and its therapy cause premature aging or contribute mechanistically to HIV-associated non-AIDS illnesses (HANA). Survival with HIV/AIDS has markedly improved by therapy combinations containing nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors, and protease inhibitors (PIs) called HAART (highly active antiretroviral therapy). Because NRTIs and PIs together prevent or attenuate HIV-1 replication, and prolong life, the population of aging patients with HIV/AIDS increases accordingly. However, illnesses frequently associated with aging in the absence of HIV/AIDS appear to occur prematurely in HIV/AIDS patients. Theories that help to explain biological aging include oxidative stress (where mitochondrial oxidative injury exceeds antioxidant defense), chromosome telomere shortening with associated cellular senescence, and accumulation of lamin A precursors (a nuclear envelop protein). Each of these has the potential to be enhanced or caused by HIV/AIDS, antiretroviral therapy, or both. Antiretroviral therapy has been shown to enhance events seen in biological aging. Specifically, antiretroviral NRTIs cause mitochondrial dysfunction, oxidative stress, and mitochondrial DNA defects that resemble features of both HANA and aging. More recent clinical evidence points to telomere shortening caused by NRTI triphosphate-induced inhibition of telomerase, suggesting telomerase reverse transcriptase (TERT) inhibition as being a pathogenetic contributor to premature aging in HIV/AIDS. PIs may also have a role in premature aging in HIV/AIDS as they cause prelamin A accumulation. Overall, toxic side effects of HAART may both resemble and promote events of aging and are worthy of mechanistic studies.

A comparison of replicative senescence and doxorubicin-induced premature senescence of vascular smooth muscle cells isolated from human aorta.

Senescence of vascular smooth muscle cells (VSMCs) contributes to aging as well as age-related diseases of the cardiovascular system. Senescent VSMCs have been shown to be present in atherosclerotic plaques. Both replicative (RS) and stress-induced premature senescence (SIPS) accompany cardiovascular diseases. We aimed to establish the signature of RS and SIPS of VSMCs, induced by a common anticancer drug, doxorubicin, and to discover the so far undisclosed features of senescent cells that are potentially harmful to the organism. Most of the senescence hallmarks were common for both RS and SIPS; however, some differences were observed. 32 % of doxorubicin-treated cells were arrested in the G2/M phase of the cell cycle, while 73 % of replicatively senescing cells were arrested in the G1 phase. Moreover, on the basis of alkaline phosphatase activity measurements, we show that a 7-day treatment with doxorubicin (dox), does not cause precocious cell calcification, which is a characteristic feature of RS. We did not observe calcification even though after 7 days of dox-treatment many other markers characteristic for senescent cells were present. It can suggest that dox-induced SIPS does not accelerate the mineralization of vessels. We consider that detailed characterization of the two types of cellular senescence can be useful in in vitro studies of potential anti-aging factors.

[Profile of P66SHC expression and histone modifications in replicative cell senescence and oxidative-stress induced premature senescence].

OBJECTIVE: To study the profile of P66SHc expression and histone modifications in replicatively senescenct cells and oxidative-stress inducing premature senescenct cells. METHODS: HPF cells were continuously cultured and subcultured in vitro to build replicative cellular model. HPF cells were treated with 200 pmol/L H2 O2 four times to build oxidative-stress inducing premature senescenct model. Comparative Q-PCR was utilized to investigate target gene (P66SHC, EP300, HDAC1) expressions respectively in H2O2 treated groups and normal cell groups. Then CHIP-QPCR was conducted to analyze histone modifications of P66SHC between young cells and aging cells. RESULTS: P66SHC expression was positive correlation with H2O2 doses and population doubling level (PDL) (R = 0.909, P = 0.000; R = 0.743, P = 0.006), while EP300 was negative correlation with H2O2 (R = - 0.922, P = 0.000) and both EP300 and HDAC1 were negative with PDL (R = -0.709, P = 0.010, R = -0.599, P = 0.040). H3 histone modifications were declined in P66SHc gene regulating region. H3-Ac, H3K9-Ac and H3K4-tri-Me were dominant in the upstream region of transcriptional site (-3.0 kb) and alternative promotor (+3.8 kb). CONCLUSION: P66SHC, EP300 and HDAC1 probably play a role in cellular replicative senescence and oxidative-stress inducing premature senescence. Besides, histone modification could regulate P66SHC gene expression.

Dietary phosphate: what do we know about its toxicity.

UNLABELLED: Inorganic phosphate (Pi) is an essential mineral required for diverse cellular processes. Recent genetic and dietary experiments in animal models indicate that Pi may be toxic to a variety of biological processes. High dietary Pi load in such animal models resulted in an increase in oxidative stress, DNA damage that resulted in phenotypic expression of premature aging, and short life span. Further, high Pi load was reported to induce carcinogenesis in lung and skin cancer animal models. So far, translational research is limited to observational studies that show an independent association of Pi intake with morbidity and mortality across all strata of kidney function. Fast-food and processed-food consumption in an average American diet leads to large increases in daily phosphate intake. Whether such dietary patterns explain the epidemiology of disease processes in humans remains to be further investigated. CONCLUSION: Phosphotoxicity is a novel concept with a potential for a large public health impact in future, but urgent studies are needed to prove reducing Pi intake to a certain target generates better clinical outcomes.

Contribution of CYP2E1 polymorphism to aging in the mechanical workshop workers.

Aging is attributed to both genetic and environmental factors. Occupational exposure is one of the environmental factors with potential genotoxic effects. Researchers try to determine factors involved in genetic damages at hazards exposure that could accelerate aging. Cytochrome P450 2E1 (CYP2E1) gene contributes in activation and detoxification of the environmental hazards. This polymorphism plays an important role in susceptibility of inter-individuals to DNA damage at the occupational exposure. The current study evaluated the possible influence of this gene polymorphism in aging by genomic damages through the biomarkers alterations of micronuclei (MN), comet tail length and telomere length shortening at the exposure. In this study, buccal cells were collected from the oral cavity of exposed workers and non-exposed controls. The CYP2E1 genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The wild genotype significantly affected MN frequency (p = 0.007) and relative telomere length (p = 0.047) in the older group of workers. It was concluded that the interaction of gene polymorphism and exposure enhances DNA damage and accelerates aging consequently.

Effect of Colla corii asini (E'jiao) on D-galactose induced aging mice.

Colla corii asini (E'jiao), donkey-hide gelatin prepared by stewing and concentrating from Equus asinus L. donkey hide, is a traditional Chinese medicine preparation widely used in clinical hematic antanemic therapy in China. The aim of the present study was to investigate potential anti-aging effect of Colla corii asini and explore related mechanisms in D-galactose (gal) induced aging model mice. The mice were artificially induced aging by subcutaneously injection with D-gal at the dose of 100 mg/kg·d for 8 weeks. Colla corii asini was simultaneously treated to them once daily by intragastric gavage. Appetite, mental condition, body weight, and organ index were observed. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as levels of malondialdehyde (MDA) in serum, brain, and liver were determined by according assay kits. Western blotting analysis was used to detect p16 and p21 expression. Results indicated that Colla corii asini could improve appetite, mental condition, body weight, and organ condition of model mice, improve SOD, CAT, and GSH-Px activities, reduce MDA levels, and modulate age-related genes expression in D-gal induced mice. Therefore, Colla corii asini may have effect to suppress the aging process through enhancing antioxidant activity, scavenging free radicals, and modulating aging-related gene expression.