Shorter men live longer: association of height with longevity and FOXO3 genotype in American men of Japanese ancestry.

OBJECTIVES: To determine the relation between height, FOXO3 genotype and age of death in humans. METHODS: Observational study of 8,003 American men of Japanese ancestry from the Honolulu Heart Program/Honolulu-Asia Aging Study (HHP/HAAS), a genetically and culturally homogeneous cohort followed for over 40 years. A Cox regression model with age as the time scale, stratified by year of birth, was used to estimate the effect of baseline height on mortality during follow-up. An analysis of height and longevity-associated variants of the key regulatory gene in the insulin/IGF-1 signaling (IIS) pathway, FOXO3, was performed in a HHP-HAAS subpopulation. A study of fasting insulin level and height was conducted in another HHP-HAAS subpopulation. RESULTS: A positive association was found between baseline height and all-cause mortality (RR = 1.007; 95% CI 1.003-1.011; P = 0.002) over the follow-up period. Adjustments for possible confounding variables reduced this association only slightly (RR = 1.006; 95% CI 1.002-1.010; P = 0.007). In addition, height was positively associated with all cancer mortality and mortality from cancer unrelated to smoking. A Cox regression model with time-dependent covariates showed that relative risk for baseline height on mortality increased as the population aged. Comparison of genotypes of a longevity-associated single nucleotide polymorphism in FOXO3 showed that the longevity allele was inversely associated with height. This finding was consistent with prior findings in model organisms of aging. Height was also positively associated with fasting blood insulin level, a risk factor for mortality. Regression analysis of fasting insulin level (mIU/L) on height (cm) adjusting for the age both data were collected yielded a regression coefficient of 0.26 (95% CI 0.10-0.42; P = 0.001). CONCLUSION: Height in mid-life is positively associated with mortality, with shorter stature predicting longer lifespan. Height was, moreover, associated with fasting insulin level and the longevity genotype of FOXO3, consistent with a mechanistic role for the IIS pathway.

Torpedoes in Parkinson's disease, Alzheimer's disease, essential tremor, and control brains.

Purkinje cell axonal swellings ("torpedoes"), described in several cerebellar disorders as well as essential tremor (ET), have not been quantified in common neurodegenerative conditions. The aim of this study was to quantify torpedoes Parkinson's disease (PD) and Alzheimer's disease (AD) compared with ET and control brains. Brains included 40 ET cases (34 cerebellar ET, 6 Lewy body variant of ET) and age-matched comparison brains (21 AD, 14 PD/diffuse Lewy body disease, 25 controls). Torpedoes were counted in 20 x 25 mm cerebellar cortical sections stained with Luxol Fast Blue/Hematoxylin and Eosin. The median number of torpedoes in cerebellar ET (12) was 12x higher than that of controls (1) and nearly 2.5x higher than in AD (5) or PD/DLBD (5) (all P < or = 0.005). Furthermore, in a logistic regression model that adjusted for age and Alzheimer's-type changes, each torpedo more than doubled the odds of having cerebellar ET (Odds ratio(cerebellar ET vs. control) = 2.57, P = 0.006), indicating that the association between increased torpedoes and cerebellar ET was independent of these Alzheimer's-type changes. Although torpedoes are increased in AD and PD, as well as cerebellar ET, the magnitude of increase in cerebellar ET is greater, and cannot be accounted for by concomitant AD or PD pathology.

The American Diabetes Association and World Health Organization classifications for diabetes: their impact on diabetes prevalence and total and cardiovascular disease mortality in elderly Japanese-American men.

OBJECTIVE: To compare the prevalence of diabetes according to the American Diabetes Association (ADA) and World Health Organization (WHO) classifications in a sample of elderly Japanese-American men; to examine the association with total and cardiovascular mortality by diabetes status using both classifications; and to determine whether the fasting or 2-h glucose measurement is a stronger predictor of adverse outcomes. RESEARCH DESIGN AND METHODS: Examinations given from 1991 to 1993 in the Honolulu Heart Program were used as baseline for these analyses. Subjects were 71-93 years of age at that time and were followed for total and cardiovascular disease mortality for up to 7 years. RESULTS: A total of approximately 66% of individuals who had diabetes by WHO criteria were missed when the ADA definition was used. The relative risks of total and cardiovascular mortality for those with versus those without diabetes were similar for both definitions; however, when fasting and postload glucose measures were analyzed as continuous variables, the 2-h measurement was a superior predictor and was independent of fasting glucose. In contrast, fasting glucose was not an independent predictor of these outcomes in the presence of the 2-h measurement. CONCLUSIONS: The prevalence of glucose metabolism abnormalities was very high among elderly Japanese-American men. The WHO classification was superior to the ADA classification in identification of subjects at high risk for adverse outcomes. Therefore, we conclude that the 2-h glucose measurement is valuable and should be retained in epidemiologic studies.