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Bendjilali N.,Rowan University | Hsueh W.-C.,University of California at San Francisco | He Q.,Pacific Health Research and Education Institute | He Q.,Kuakini Medical Center | And 14 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2014

Isolated populations have advantages for genetic studies of longevity from decreased haplotype diversity and long-range linkage disequilibrium. This permits smaller sample sizes without loss of power, among other utilities. Little is known about the genome of the Okinawans, a potential population isolate, recognized for longevity. Therefore, we assessed genetic diversity, structure, and admixture in Okinawans, and compared this with Caucasians, Chinese, Japanese, and Africans from HapMap II, genotyped on the same Affymetrix GeneChip Human Mapping 500K array. Principal component analysis, haplotype coverage, and linkage disequilibrium decay revealed a distinct Okinawan genome-more homogeneity, less haplotype diversity, and longer range linkage disequilibrium. Population structure and admixture analyses utilizing 52 global reference populations from the Human Genome Diversity Cell Line Panel demonstrated that Okinawans clustered almost exclusively with East Asians. Sibling relative risk (λs) analysis revealed that siblings of Okinawan centenarians have 3.11 times (females) and 3.77 times (males) more likelihood of centenarianism. These findings suggest that Okinawans are genetically distinct and share several characteristics of a population isolate, which are prone to develop extreme phenotypes (eg, longevity) from genetic drift, natural selection, and population bottlenecks. These data support further exploration of genetic influence on longevity in the Okinawans. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America.\.

Genkinger J.M.,Columbia University | Spiegelman D.,Harvard University | Anderson K.E.,University of Minnesota | Bernstein L.,City of Hope National Medical Center | And 27 more authors.
International Journal of Cancer | Year: 2011

Epidemiologic studies of pancreatic cancer risk have reported null or nonsignificant positive associations for obesity, while associations for height have been null. Waist and hip circumference have been evaluated infrequently. A pooled analysis of 14 cohort studies on 846,340 individuals was conducted; 2,135 individuals were diagnosed with pancreatic cancer during follow-up. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Compared to individuals with a body mass index (BMI) at baseline between 21-22.9 kg/m2, pancreatic cancer risk was 47% higher (95%CI:23-75%) among obese (BMI ≤yen; 30 kg/m2) individuals. A positive association was observed for BMI in early adulthood (pooled multivariate [MV]RR = 1.30, 95%CI = 1.09-1.56 comparing BMI ≤yen; 25 kg/m2 to a BMI between 21 and 22.9 kg/m2). Compared to individuals who were not overweight in early adulthood (BMI < 25 kg/m 2) and not obese at baseline (BMI < 30 kg/m2), pancreatic cancer risk was 54% higher (95%CI = 24-93%) for those who were overweight in early adulthood and obese at baseline. We observed a 40% higher risk among individuals who had gained BMI ≤yen; 10 kg/m2 between BMI at baseline and younger ages compared to individuals whose BMI remained stable. Results were either similar or slightly stronger among never smokers. A positive association was observed between waist to hip ratio (WHR) and pancreatic cancer risk (pooled MVRR = 1.35 comparing the highest versus lowest quartile, 95%CI = 1.03-1.78). BMI and WHR were positively associated with pancreatic cancer risk. Maintaining normal body weight may offer a feasible approach to reducing morbidity and mortality from pancreatic cancer. Copyright © 2010 UICC.

Robine J.-M.,French Institute of Health and Medical Research | Herrmann F.R.,University of Geneva | Arai Y.,Keio University | Willcox D.C.,Okinawa International University | And 8 more authors.
Experimental Gerontology | Year: 2012

The purpose of this study was to examine the impact of physical geographic factors and climate conditions on human longevity. The centenarian rate (CR) in 2005 was computed for Japan's 47 prefectures, whose geography and climate vary greatly. Several pathways, such as excess winter mortality, land use and agricultural production, possibly linking physical and climate factors with extreme longevity, were explored. The probability of becoming a centenarian varies significantly among the Japanese prefectures. In particular, the computation of CR70 demonstrated that the actual probability for individuals 70years old in 1975 of becoming centenarians in 2005 was 3 times higher, on average, in Okinawa, both for males and females, than in Japan as a whole. About three quarters of the variance in CR70 for females and half for males is explained by the physical environment and land use, even when variations in the level of socio-economic status between prefectures are controlled. Our analysis highlighted two features which might have played an important role in the longevity observed in Okinawa. First, there is virtually no winter in Okinawa. For instance, the mean winter temperature observed in 2005 was 17.2°C. Second, today, there is almost no rice production in Okinawa compared to other parts of Japan. In the past, however, production was higher in Okinawa. If we consider that long term effects of harsh winters can contribute to the mortality differential in old age and if we consider that food availability in the first part of the 20th century was mainly dependent on local production, early 20th century birth cohorts in Okinawa clearly had different experiences in terms of winter conditions and in terms of food availability compared to their counterparts in other parts of Japan. This work confirms the impact of climate conditions on human longevity, but it fails to demonstrate a strong association between longevity and mountainous regions and/or air quality. © 2012 Elsevier Inc.

Suzuki M.,Okinawa Research Center for Longevity Science | Suzuki M.,Okinawa International University | Suzuki M.,University of Ryukyus | Willcox D.C.,Okinawa Research Center for Longevity Science | And 8 more authors.
Current Gerontology and Geriatrics Research | Year: 2010

Background. The Free Radical Theory of Aging mechanistically links oxidative stress to aging. Okinawa has among the world's longest-lived populations but oxidative stress in this population has not been well characterized. Methods. We compared plasma lipid peroxide (LPO) and vitamin Eplasma and intracellular tocopherol levels (total α, β, and γ), in centenarians with younger controls. Results. Both LPO and vitamin E tocopherols were lower in centenarians, with the exception of intracellular β-tocopherol, which was significantly higher in centenarians versus younger controls. There were no significant differences between age groups for tocopherol: cholesterol and tocopherol: LPO ratios. Correlations were found between α-Tocopherol and LPO in septuagenarians but not in centenarians. Conclusions. The low plasma level of LPO in Okinawan centenarians, compared to younger controls, argues for protection against oxidative stress in the centenarian population and is consistent with the predictions of the Free Radical Theory of Aging. However, the present work does not strongly support a role for vitamin E in this phenomenon. The role of intracellular β-tocopherol deserves additional study. More research is needed on the contribution of oxidative stress and antioxidants to human longevity. Copyright © 2010 Makoto Suzuki et al.

Robine J.-M.,French Institute of Health and Medical Research | Herrmann F.R.,University of Geneva | Arai Y.,Keio University | Willcox D.C.,Okinawa International University | And 8 more authors.
Experimental Gerontology | Year: 2013

This response letter addresses two points raised by le Bourg when discussing our previous paper entitled "Exploring the impact of climate on human longevity". First, the arguments explaining the accuracy of the numbers of centenarian in Okinawa are developed, and second the composition and healthfulness of the traditional Okinawan diet are described as well as the changes in dietary pattern and their impact on longevity. © 2013 Elsevier Inc.

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