Modulation of infection-induced inflammation and locomotive deficit and longevity in senescence-accelerated mice-prone (SAMP8) model by the oligomerized polyphenol Oligonol.

Oligonol is produced from the oligomerization of polyphenols (typically proanthocyanidin from a variety of fruits such as lychees, grapes, apples, persimmons, etc.) and contains catechin-type monomers and oligomers of proanthocyanidins. The ability of Oligonol to affect infection-dependent eye inflammation, locomotion and longevity in senescence-accelerated prone mice (SAMP8) (a model of senescence acceleration and geriatric disorders with increased oxidative stress and neuronal deficit) was investigated. Oligonol (60mg/kg) significantly modulated the extent of inflammation scores in the eye of SAMP8 mice. Examination of the mice indicated infection with mouse hepatitis virus and pinworm (Syphacia obvelata) in both males and females and with the intestinal protozoa (trichomonad) in males. A comparison of the two groups (using log-rank test) and the difference in the mean life span between groups (using Student's t-test) indicated significant differences in survival (p=0.043) and the mean life span (p=0.033) in male SAMP8 mice. Oligonol increased the mean life span and this was statistically significant. In the open-field locomotive test, the 7-week-old SAMP8 mice crossed more than 40 partitioned lines in 1min. At 48-week-old control untreated male SAMP8 crossed 2 lines. The Oligonol-treated 48-week-old male SAMP8 mice crossed 17 lines however. The improved locomotive activity was statistically significant even after 36weeks in the Oligonol-treated male SAMP8 but this was not the case throughout the time course of the study in the Oligonol-treated female SAMP8. Thus Oligonol treatment to SAMP8 mice modulated the severity of infection-dependent inflammation, prolonged life-span and significantly improved locomotive activity indicating potential benefit to aging-associated diseases such as Alzheimer's or Parkinson's diseases. This presents potential for further research to define infection-dependent inflammation associated with degenerative conditions and the molecular mechanism of dietary antioxidant protection.     

Does exposure to infectious diseases in infancy affect old-age mortality? Evidence from a pre-industrial population

Many studies have shown that health conditions experienced in childhood play an important role on an individual's adult mortality. Recent research suggests that past reductions in early life exposure to infectious diseases have been a major contributor to the historical decline in old-age mortality. Drawing on French-Canadian data from cohorts born in the 17th and 18th centuries, we test whether a progressive deterioration in early life conditions (as revealed by an increasing infant mortality rate) translates into a decrease in survival prospects in late life. We use traditional demographic measures such as the age-specific probability of death, and a series of proportional hazard models to control for familial and environmental conditions. Results point toward little evidence of any early life effects. The trend of increasing infant mortality does not correlate with a general increase of mortality in older ages within the same cohorts. Period changes affecting survival at older ages (war, epidemics) as well as demographic and biological characteristics shared within families have a much larger role in old-age mortality than early life characteristics shared within the same cohorts.     

Candidate genes associated with ageing and life expectancy in the Jerusalem longitudinal study

In an exploratory study, 11 common polymorphisms were examined for contributing to longevity including: apolipoprotein E (apoE), methylenetetrahydrofolate reductase (MTHFR), cathepsin D (CAD), superoxide dismutase 2 (SOD2), angiotensinogen (AGT) and insulin-like growth factor 2 (IGF2), Leiden factor 7, p53 oncogene, dopamine D4 receptor (DRD4) and the serotonin transporter (SERT). Genotype and allele frequencies of these genes were compared in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity to a group of 441 younger subjects (22 years). Nominally significant results provide suggestive evidence in the Ashkenazi group that apoE, MHTFR, SOD2, IGF2 ApaI, and factor VII are risk factors for a single outcome, survival to 75. Overall, the more genetically homogenous Ashkenazi ethnic group showed evidence for association in five genes examined suggesting that future studies in this population would gainfully focus on this ethnic group.     

Increased poly(ADP-ribose) polymerase activity in lymphoblastoid cell lines from centenarians

 Poly(ADP-ribosyl)ation is a posttranslational modification of nuclear proteins which is catalyzed by poly(ADP-ribose) polymerase and represents an immediate response of eukaryotic cells to oxidative and other types of DNA damage. Previously a strong correlation had been detected between maximal poly(ADP-ribose) polymerase activity in permeabilized mononuclear leukocytes of various mammalian species and species-specific life span. To study a possible relation between longevity and poly(ADP-ribosyl)ation in humans we measured maximal oligonucleotide-stimulated poly(ADP-ribose) polymerase activity in permeabilized, Epstein-Barr virus transformed lymphoblastoid cell lines from a French population of 49 centenarians and 51 controls aged 20–70 years. Maximal enzyme activity was significantly higher in centenarians than in controls [median of controls: 9035 cpm/10⁶ cells (lower quartile: 6156; upper quartile: 11,410); median of centenarians: 10,380 cpm/10⁶ cells (lower quartile: 7994; upper quartile: 12,991); P=0.031 by Mann-Whitney U test]. In a subset of 16 controls and 24 centenarians, cellular poly(ADP-ribose) polymerase content was determined by quantitative western blotting, thus allowing the calculation of specific enzyme activity. The latter was significantly higher in centenarians (P=0.006), the median value for centenarians being about 1.6-fold that of controls. Specific poly(ADP-ribose) polymerase activity was a more powerful parameter for differentiating between centenarians and controls than enzyme activity relative to cell number. In addition, in a genetic association study we analyzed 437 DNA samples (239 centenarians and 198 controls) by PCR amplification of a polymorphic dinucleotide repeat located in the promoter region of the poly(ADP-ribose) polymerase gene in an attempt to detect an association between this polymorphic marker and variability of enzyme activity or human longevity. However, this genetic analysis revealed no significant enrichment of any of the alleles or genotypes identified among centenarians or controls, but its power was limited by the relatively weak hetero-zygosity of this polymorphic marker in our population (51%). Viewed together with previous results on poly(ADP-ribose) polymerase activity in various mammalian species, the present data provide further evidence for the notion that longevity is associated with a high poly(ADP-ribosyl)ation capacity. Received: 5 September 1997 / Accepted: 10 November 1997     

Extreme weather and mortality: Evidence from two millennia of Chinese elites

Modern technology empowers human beings to cope with various extreme weather events. Using Chinese historical data, we examine the impact of extreme weather on long-term human mortality in an environment where individuals had no access to modern technology. By combining life-course data on 5000 Chinese elites with historical weather data over the period 1–1840 AD, we find a significant and robust negative impact of droughts in childhood on the longevity of elites. Quantitatively, encountering three years of droughts in childhood reduces an elite's life span by about two years.     

广西壮族自治区多地区长寿人群分布特征及其相关因素研究

目的探索我国典型长寿地区人群中与健康长寿的相关因素,为老年人群的健康长寿提供有价值的参考数据。方法采用登记和入户问卷调查方法收集和解析广西壮族自治区桂林市永福县、河池市巴马县和防城港市东兴市长寿老人(≥90岁)的人口学基本特征;然后在当地一般人群中,随机选取年龄组对照(40~85岁)。分别对比长寿和对照人群的性别、民族、家族史、疾病史、婚姻状况、家庭代数和子女数、吸烟、饮酒、外出活动、睡眠等与健康长寿相关因素进行关联分析。结果在巴马县、永福县和东兴市常住人口69.15万人中,共登记有≥90岁者1005例(≥90岁率:145.34/10万),其中≥90岁和<100岁(长寿)者944例(长寿率:136.51/10万),年龄(93.28±2.57)岁;≥100岁者61例(百岁率:8.82/10万),年龄(102.00±3.05)岁。长寿和百岁比较仅有3个因素如,地区分布(P=0.014)、无疾病史(P=0.002)和家庭代数(P=0.008)有显著关联。表明长寿和百岁人群可能是同一群体,合并两者将长寿+百岁和对照比较,与健康长寿有显著关联的因素有已婚(OR=26.469,95%CI:13.208~53.045)、家庭代数(OR=5.419,95%CI:3.418~8.592)、儿子数(OR=2.013,95%CI:1.555~2.607)、女儿数(OR=1.380,95%CI:1.122~1.696)和外出活动(OR=10.226,95%CI:3.164~33.045)。结论广西壮族自治区巴马县、永福县和东兴市一般自然人群中长寿和百岁率较高;可能得益于多子女和多代的家庭结构,并且乐观的心态、运动和生活规律均可能是其中重要的健康长寿关联因素。     

Unusual Longevity Without Surgical Intervention in Complete Transposition of the Great Arteries

A case of unusual longevity to the age of 58 years is reported for a female patient with complete transposition of the great arteries. The association with a wide atrial septal defect with intact interventricular septum may have contributed to the long survival without surgery. Factors determining intercirculatory mixing and systemic oxygen saturation may be the high pulmonary flow, the location of the anatomic communication, sufficient hemoglobin concentration to allow an adequate level of systemic resistance and recirculated systemic flow, and the belated development of pulmonary vascular disease.     

3种不同人参胶囊对果蝇寿命的影响

[目的]探讨不同人参胶囊延缓O regon K野生型黑腹果蝇衰老的作用。[方法]收集8 h内乳化未交配雌雄果蝇6 000只,雌雄各半,随机分配在A、B、C 3种人参胶囊的各自4个浓度组中,每个浓度组雌雄果蝇各200只,每4d更换1次培养基,每2 d计数1次,用生存试验检测果蝇寿命。[结果]A胶囊0.06%、0.20%和0.60%浓度组的雌性果蝇与对照组比较延长平均寿命2.4~5.3 d,延长雌蝇平均最高寿命为3.4~8.8 d;B胶囊0.120%和0.360%浓度组雌蝇与对照组比较平均寿命延长2.5~3.6 d,且延长平均最高寿命为2.4~3.4 d;0.120%浓度组雄蝇与对照组比较延长平均最高寿命为2.8 d;C胶囊0.24%和0.72%浓度组雌蝇与对照组比较延长平均寿命2.96~3.55 d,0.24%浓度组雌蝇与对照组比较延长平均最高寿命3.45 d;0.08%浓度组雄蝇与对照组比较延长平均寿命2.97 d(P<0.05或P<0.01)。[结论]人参能延长O regon K野生型黑腹果蝇的寿命。     

Association of exceptional parental longevity and physical function in aging

Offspring of parents with exceptional longevity (OPEL), who are more likely to carry longevity-associated genotypes, may age more successfully than offspring of parents with usual survival (OPUS). Maintenance of physical function is a key attribute of successful aging. While many genetic and non-genetic factors interact to determine physical phenotype in aging, examination of the contribution of exceptional parental longevity to physical function in aging is limited. The LonGenity study recruited a relatively genetically homogenous cohort of Ashkenazi Jewish (AJ) adults age 65 and older, who were defined as either OPEL (having at least one parent who lived to age 95 or older) or OPUS (neither parent survived to age 95). Subjective and objective measures of physical function were compared between the two groups, accounting for potential confounders. Of the 893 LonGenity subjects, 365 were OPEL and 528 were OPUS. OPEL had better objective and subjective measures of physical function than OPUS, especially on unipedal stance (p = 0.009) and gait speed (p = 0.002). Results support the protective role of exceptional parental longevity in preventing decline in physical function, possibly via genetic mechanisms that should be further explored.     

Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis

This systematic review investigated whether the insulin sensitiser metformin has a geroprotective effect in humans. Pubmed and Embase were searched along with databases of unpublished studies. Eligible research investigated the effect of metformin on all-cause mortality or diseases of ageing relative to non-diabetic populations or diabetics receiving other therapies with adjustment for disease control achieved. Overall, 260 full-texts were reviewed and 53 met the inclusion criteria. Diabetics taking metformin had significantly lower all-cause mortality than non-diabetics (hazard ratio (HR) = 0.93, 95%CI 0.88–0.99), as did diabetics taking metformin compared to diabetics receiving non-metformin therapies (HR = 0.72, 95%CI 0.65–0.80), insulin (HR = 0.68, 95%CI 0.63–0.75) or sulphonylurea (HR = 0.80, 95%CI 0.66–0.97). Metformin users also had reduced cancer compared to non-diabetics (rate ratio = 0.94, 95%CI 0.92–0.97) and cardiovascular disease (CVD) compared to diabetics receiving non-metformin therapies (HR = 0.76, 95%CI 0.66–0.87) or insulin (HR = 0.78, 95%CI 0.73–0.83). Differences in baseline characteristics were observed which had the potential to bias findings, although statistical adjustments were made. The apparent reductions in all-cause mortality and diseases of ageing associated with metformin use suggest that metformin could be extending life and healthspans by acting as a geroprotective agent.