端粒长度与癌症、衰老及膳食因素的相关性研究进展

目的 综述人群中端粒长度与癌症、衰老相关疾病和膳食因素的相关性。方法 通过“端粒长度”、“癌症”、“衰老”、“膳食因素”等中文关键词及对应的英文关键词在CNKI、pubmed等数据库中进行文献检索,筛选高质量的流行病学研究。结果 端粒长度与人群癌症发病风险及死亡风险相关,与某些癌症发病风险之间可能存在U型关联;较短的端粒与心脑血管疾病的高发病风险及多种衰老相关疾病的不良预后相关;膳食因素中单一食物组分与人群中端粒长度的关系存在争议,尚需要前瞻性研究进一步探讨。结论 端粒长度具有作为多种疾病临床治疗预后生物标志物的应用潜能;前瞻性队列随访研究有助于发现膳食因素与端粒长度之间的因果关系。     

端粒、端粒酶及靶向抗衰老研究

端粒是细胞染色体末端一段高度保守的重复核苷酸序列,在基因结构的完整性及染色体稳定性方面起重要作用。端粒酶是具有逆转录酶活性的核糖核蛋白复合体,它合成端粒重复序列添至染色体末端,维持端粒长度。端粒长度与细胞衰老密切相关,是分子老化的标志物,基于端粒酶延长端粒长度是近年来抗衰老的研究热点。因此,本文查阅近几年来有关端粒与衰老研究相关文献,对端粒及端粒酶生物学功能和影响因素及与衰老关联作一归纳总结,并探讨以端粒酶为靶点的抗衰老治疗的最新进展,对今后抗衰老研究作出展望。     

老年前期健康人群营养素摄入及免疫功能情况探讨

目的研究与探讨老年前期健康人群营养素摄入及免疫功能情况。方法对73例45-60岁老年前期健康者的营养素摄入及免疫功能情况进行调查研究,分析营养素摄入情况与免疫功能指标的相关性。结果将所选73例老年前期健康者的营养素摄入与免疫功能指标进行多元线性回归分析表明,营养素摄入与免疫功能指标具有相关性,其中血清IgG与维生素B1摄入呈负相关,IgA与脂肪摄入呈负相关,IgM与硒摄入呈正相关,CD3+CD4+与维生素A摄入呈负相关,CD3+CD8+与维生素C摄入呈正相关,CD3+CD4+/CD3+CD8+与维生素C摄入呈负相关,IL-2与维生素E摄入呈正相关,TNF-α与维生素A摄入呈正相关,吞噬百分率与维生素A摄入呈正相关,与铁摄入呈负相关,吞噬指数与铜摄入呈正相关,与铁摄入呈负相关。结论老年前期健康人群的营养素摄入与免疫功能情况具有相关性,合理的膳食搭配和干预措施能够有效延缓免疫功能衰老情况的发生。     

不容忽视的『非必需营养素』

大家都知道，蛋白质、脂肪、糖类(又称碳水化合物)、维生素、矿物质和水是人体不可缺少的营养素，它们被称为人体必需营养素。营养学研究发现，适量摄入各种必需营养素才能有益健康，而且食物中还有许多“非必需营养素”，它们虽然不属于上述六大类营养素，但可以预防肿瘤、心血管疾病、糖尿病等慢性疾病，以及延缓人体衰老、提高免疫力，在膳食中的     

中老年人群抗氧化营养素摄入与体内抗氧化功能的探讨

了解中老年人群膳食中抗氧化营养素的摄入状况及体内抗氧化功能水平。 [方法 ]　对上海某社区 2 2 9名 45～ 79岁老年前期和老年期人群开展营养学调查和血清学分析。 [结果 ]　两组人群从膳食中摄入的抗氧化营养素不能满足需要 ,体内血清超氧化物歧化酶 (SOD)普遍降低 ,而脂质过氧化产物 (MDA)则普遍升高。[结论 ]　衰老与年龄、抗氧化营养素摄入不足有关 ,中老年人群应增加抗氧化营养素的摄入 ,必要时使用抗氧化营养合剂。抗衰老应从中年人开始。     

端粒与细胞衰老

端粒是现代生物学研究的热点,端粒封闭了染色体的末端并维持了染色体的稳定性,端粒的缺失与细胞的衰老有密切的关系。本文就端粒的结构和功能与细胞老化的关系进行了综述。     

体育锻炼可预防循环中白细胞和血管壁细胞的衰老

背景 体育锻炼对血管保护作用的潜在分子机制尚未完全清楚。端粒消耗是衰老的一个中心部分。端粒相关蛋白可调节细胞的衰老和存活。该研究评价了，运动对小鼠血管端粒生物学和内皮细胞凋亡的作用，以及长期耐力训练对人体端粒生物学的作用。方法和结果该研究将C57／B16小鼠随机分配至可自由跑动或无跑轮的环境中，对其研究3周。与无运动的对照组相比，运动上调了胸主动脉和循环中单核细胞的端粒酶活性，     

水果、蔬菜或可减缓肌萎缩侧索硬化症

正哥伦比亚大学研究人员发现,水果和蔬菜等食物中含有大量的抗氧化营养素和类胡萝卜素,或可明显改善肌萎缩侧索硬化症(ALS)患者机体的功能。肌萎缩侧索硬化症是一种严重的神经变性疾病。研究人员检测了营养素的摄入和ALS症状持续18个月或更少时间的患者机体疾病严重程度的关系。结果发现,营养素在诱发疾病以及疾病进展过程中扮演着重要角色。研究人员指出,ALS患者应当摄入含有较高水平抗     

硒与人体健康的研究进展

硒是人体三大抗氧化营养素之一,也是人体必需的微量元素.硒具有抗氧化、消除自由基、增强机体免疫等多种生理功能,同时在重金属解毒、保护心肌和心血管以及抗癌等方面也起到极为重要的作用.适当增加硒的摄入量,对维持身体健康、预防衰老、防治某些疾病的发生都具有重要意义.硒对机体具有双重作用,过量的摄入和补充硒可以导致硒中毒发生,应给与重视.     

胃癌患者营养素摄入对其生活质量的影响

[目的]了解术后1～2年胃癌患者的生活质量、摄入的营养素对其生活质量的影响和影响营养素摄入的因素。[方法]对长乐市2002—2003年手术后存活1年以上的287例胃癌患者用自编问卷进行人户调查．用多元线性回归分析和方差分析法研究患者营养素摄入与生活质量的关系,以及影响营养素摄入的因素。[结果]影响胃癌患者生活质量的因素有：性别,家庭人均月收入、辅助免疫治疗、康复锻炼和营养素(包括蛋白质、铁、锌、硒、核黄素及烟酸);每日用餐数、家庭人均月收入与摄入的营养素含量有统计学意义。[结论]胃癌患者的营养状况对生活质量有影响;增加每日餐次．增加营养素摄入．可提高患者的生活质量。     

Promoter methylation of E-cadherin, p16, and RAR-β(2) genes in breast tumors and dietary intake of nutrients important in one-carbon metabolism

Aberrant DNA methylation plays a critical role in carcinogenesis, and the availability of dietary factors involved in 1-carbon metabolism may contribute to aberrant DNA methylation. We investigated the association of intake of folate, vitamins B(2), B(6), B(12), and methionine with promoter methylation of E-cadherin, p16, and RAR-β(2) genes in archived tumor tissues from incident, primary breast cancer cases in a population-based case-control study. Real-time methylation-specific PCR was performed on 803 paraffin-embedded samples; usual dietary intake was queried from a food frequency questionnaire. Unconditional logistic regression was used to derive adjusted odds ratios and 95% confidence intervals for likelihood of promoter methylation for high compared to low intake of those 1-carbon nutrients. Overall, in case-case comparisons, dietary intakes of folate, vitamins B(2), B(6), B(12), and methionine were not associated with likelihood of promoter methylation of E- cadherin, p16, and RAR-β(2) for all cases combined or within strata defined by menopausal status and estrogen receptor status in this study. This finding, however, does not exclude the possibility that intake of such nutrients might have the ability to modulate promoter methylation in normal or premalignant (dysplastic) breast tissue.     

DNA甲基化与衰老研究进展

DNA甲基化与衰老的研究是近20a来分子生物学研究的热点之一。本文综述了近年来国内外文献，概括DNA甲基化理论研究进展，探讨影响甲基化与衰老的主要因素，以揭示两者之间可能存在的联系，并分析了与甲基化和衰老相关疾病的发生机制。     

Promoter Methylation of E-Cadherin,p16, and RAR-β2 Genes in Breast Tumors and Dietary Intake of Nutrients Important in One-Carbon Metabolism

Aberrant DNA methylation plays a critical role in carcinogenesis, and the availability of dietary factors involved in 1-carbon metabolism may contribute to aberrant DNA methylation. We investigated the association of intake of folate, vitamins B₂, B₆, B₁₂, and methionine with promoter methylation of E-cadherin, p16, and RAR-β₂ genes in archived tumor tissues from incident, primary breast cancer cases in a population-based case-control study. Real-time methylation-specific PCR was performed on 803 paraffin-embedded samples; usual dietary intake was queried from a food frequency questionnaire. Unconditional logistic regression was used to derive adjusted odds ratios and 95% confidence intervals for likelihood of promoter methylation for high compared to low intake of those 1-carbon nutrients. Overall, in case-case comparisons, dietary intakes of folate, vitamins B₂, B₆, B₁₂, and methionine were not associated with likelihood of promoter methylation of E- cadherin, p16, and RAR-β₂ for all cases combined or within strata defined by menopausal status and estrogen receptor status in this study. This finding, however, does not exclude the possibility that intake of such nutrients might have the ability to modulate promoter methylation in normal or premalignant (dysplastic) breast tissue.     

Dietary patterns are associated with levels of global genomic DNA methylation in a cancer-free population

Animal studies have provided direct evidence that dietary factors induce changes in DNA methylation patterns. In humans, studies on diet and DNA methylation have yielded inconsistent findings. Because humans tend to consume foods and nutrients that are highly interrelated, study of dietary patterns may have improved the power of detecting the effect of diet on DNA methylation. Using data collected from 149 participants aged 45-75 y in the North Texas Healthy Heart Study, we examined the relationship between dietary patterns and levels of genomic DNA methylation in peripheral blood leukocytes. Dietary data were collected from study participants using the Block FFQ. Genomic DNA methylation was measured using bisulfite conversion of DNA and real-time PCR (MethyLight) for LINE-1. Two dietary patterns were identified using factor analysis: a "prudent" dietary pattern characterized by a high intake of vegetables and fruits, and a "Western" dietary pattern characterized by a high intake of meats, grains, dairy, oils, and potatoes. The prudent dietary pattern was associated with a lower prevalence of DNA hypomethylation (Q(4) vs. Q(1); OR = 0.33, 95% CI: 0.12-0.92) and the association was dose dependent (P-trend = 0.04). There was no apparent association between the Western dietary pattern and global leukocyte DNA methylation (Q(4) vs. Q(1); OR = 1.28, 95% CI: 0.47-3.47; P-trend = 0.55). Thus, a dietary pattern characterized by a high intake of vegetables and fruits may protect against global DNA hypomethylation. Future studies with a larger sample size need to confirm that this association holds longitudinally.     

Maternal one-carbon nutrient intake and cancer risk in offspring

Dietary intake of one-carbon nutrients, particularly folate, vitamin B(2) (riboflavin), vitamin B(6) , vitamin B(12) , and choline have been linked to the risk of cancers of the colon and breast in both human and animal studies. More recently, experimental and epidemiological data have emerged to suggest that maternal intake of these nutrients during gestation may also have an impact on the risk of cancer in offspring later in life. Given the plasticity of DNA methylation in the developing embryo and the established role of one-carbon metabolism in supporting biological methylation reactions, it is plausible that alterations in maternal one-carbon nutrient availability might induce subtle epigenetic changes in the developing embryo and fetus that persist into later life, altering the risk of tumorigenesis throughout the lifespan. This review summarizes the current literature on maternal one-carbon nutrient intake and offspring cancer risk, with an emphasis on cancers of the colon and breast, and discusses specific epigenetic modifications that may play a role in their pathogenesis.     

Nutritional influences on epigenetics and age-related disease

Nutritional epigenetics has emerged as a novel mechanism underlying gene-diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modulates gene expression without changes in the underlying bp sequence, ultimately determining phenotype from genotype. DNA methylation and post-translational histone modifications are classical levels of epigenetic regulation. Epigenetic phenomena are critical from embryonic development through the aging process, with aberrations in epigenetic patterns emerging as aetiological mechanisms in many age-related diseases such as cancer, CVD and neurodegenerative disorders. Nutrients can act as the source of epigenetic modifications and can regulate the placement of these modifications. Nutrients involved in one-carbon metabolism, namely folate, vitamin B12, vitamin B6, riboflavin, methionine, choline and betaine, are involved in DNA methylation by regulating levels of the universal methyl donor S-adenosylmethionine and methyltransferase inhibitor S-adenosylhomocysteine. Other nutrients and bioactive food components such as retinoic acid, resveratrol, curcumin, sulforaphane and tea polyphenols can modulate epigenetic patterns by altering the levels of S-adenosylmethionine and S-adenosylhomocysteine or directing the enzymes that catalyse DNA methylation and histone modifications. Aging and age-related diseases are associated with profound changes in epigenetic patterns, though it is not yet known whether these changes are programmatic or stochastic in nature. Future work in this field seeks to characterise the epigenetic pattern of healthy aging to ultimately identify nutritional measures to achieve this pattern.     

Older age and dietary folate are determinants of genomic and p16-specific DNA methylation in mouse colon

Older age and inadequate folate intake are strongly implicated as important risk factors for colon cancer and each is associated with altered DNA methylation. This study was designed to determine the effects of aging and dietary folate on select features of DNA methylation in the colon that are relevant to carcinogenesis. Old (18 mo; n = 34) and young (4 mo; n = 32) male C57BL/6 mice were randomly divided into 3 groups and fed diets containing 0, 4.5, or 18 mumol folate/kg (deplete, replete, and supplemented groups, respectively) for 20 wk. Genomic DNA methylation and p16 promoter methylation in the colonic mucosa were analyzed by liquid chromatography/electrospray ionization/MS and methylation-specific PCR, respectively. p16 gene expression was determined by real-time RT-PCR. Old mice had significantly lower genomic DNA methylation compared with young mice at each level of dietary folate (4.5 +/- 0.2, 4.8 +/- 0.1, and 4.9 +/- 0.1 vs. 6.0 +/- 0.1, 5.3 +/- 0.2, and 5.9 +/- 0.2%, in folate-deplete, -replete, and -supplemented groups, respectively, P < 0.05) and markedly higher p16 promoter methylation (61.0 +/- 2.7, 69.7 +/- 6.9, and 87.1 +/- 13.4 vs. 10.8 +/- 3.6, 8.4 +/- 1.8, and 4.9 +/- 1.7%, respectively, P < 0.05). In old mice, genomic and p16 promoter DNA methylation each increased in a manner that was directly related to dietary folate (P(trend) = 0.009). Age-related enhancement of p16 expression occurred in folate-replete (P = 0.001) and folate-supplemented groups (P = 0.041), but not in the folate-deplete group. In conclusion, aging decreases genomic DNA methylation and increases promoter methylation and expression of p16 in mouse colons. This effect is dependent on the level of dietary folate.     

Epigenetics: A New Bridge between Nutrition and Health

Nutrients can reverse or change epigenetic phenomena such as DNA methylation and histone modifications, thereby modifying the expression of critical genes associated with physiologic and pathologic processes, including embryonic development, aging, and carcinogenesis. It appears that nutrients and bioactive food components can influence epigenetic phenomena either by directly inhibiting enzymes that catalyze DNA methylation or histone modifications, or by altering the availability of substrates necessary for those enzymatic reactions. In this regard, nutritional epigenetics has been viewed as an attractive tool to prevent pediatric developmental diseases and cancer as well as to delay aging-associated processes. In recent years, epigenetics has become an emerging issue in a broad range of diseases such as type 2 diabetes mellitus, obesity, inflammation, and neurocognitive disorders. Although the possibility of developing a treatment or discovering preventative measures of these diseases is exciting, current knowledge in nutritional epigenetics is limited, and further studies are needed to expand the available resources and better understand the use of nutrients or bioactive food components for maintaining our health and preventing diseases through modifiable epigenetic mechanisms.     

Nutritional Epigenomics: A Portal to Disease Prevention

Epigenetics can be defined as inheritable and reversible phenomena that affect gene expression without altering the underlying base pair sequence. Epigenomics is the study of genome-wide epigenetic modifications. Because gene expression changes are critical in both normal development and disease progression, epigenetics is widely applicable to many aspects of biological research. The influences of nutrients and bioactive food components on epigenetic phenomena such as DNA methylation and various types of histone modifications have been extensively investigated. Because an individual’s epigenetic patterns are established during early gestation and are changed and personalized by environmental factors during our lifetime, epigenetic mechanisms are quite important in the development of transgenerational and adult obesity as well as in the development of diabetes mellitus. Aging and cancer demonstrate profound genome-wide DNA methylation changes, suggesting that nutrition may affect the aging process and cancer development through epigenetic mechanisms.     

Dietary intake and arsenic methylation in a U.S. population

Millions of people worldwide are exposed to arsenic-contaminated drinking water, and ingestion of inorganic arsenic (InAs) has been associated with increased risks of cancer. The primary metabolic pathway of ingested InAs is methylation to monomethyl arsenic (MMA) and dimethyl arsenic (DMA). However, people vary greatly in the degree to which they methylate InAs, and recent evidence suggests that those who excrete high proportions of ingested arsenic as MMA are more susceptible than others to arsenic-caused cancer. To date, little is known about the factors that determine interindividual differences in arsenic methylation. In this study, we assessed the effect of diet on arsenic metabolism by measuring dietary intakes and urinary arsenic methylation patterns in 87 subjects from two arsenic-exposed regions in the western United States. Subjects in the lower quartile of protein intake excreted a higher proportion of ingested InAs as MMA (14.6 vs. 11.6%; p = 0.01) and a lower proportion as DMA (72.3 vs. 77.0%; p = 0.01) than did subjects in the upper quartile of protein intake. Subjects in the lower quartile of iron, zinc, and niacin intake also had higher urinary percent MMA and lower percent DMA levels than did subjects with higher intakes of these nutrients. These associations were also seen in multivariate regression analyses adjusted for age, sex, smoking, and total urinary arsenic. Given the previously reported links between high percent MMA and increased cancer risks, these findings are consistent with the theory that people with diets deficient in protein and other nutrients are more susceptible than others to arsenic-caused cancer.