Shorter Men Live Longer: Association of Height with Longevity and FOXO3 Genotype in American Men of Japanese Ancestry

Abstract

ObjectivesTo determine the relation between height, FOXO3 genotype and age of death in humans.MethodsObservational 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.ResultsA 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).ConclusionHeight 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.

Global effects of income and income inequality on adult height and sexual dimorphism in height

“…Rather, it is that, " modern medicine and improved sanitation have sharply reduced infant, maternal and childhood mortality" (Samaras 2012, p. 248). A direct association study by He and colleagues (He et al, 2014) reports that shorter adult height is associated with greater longevity in both Japanese and American men.…”

“…Rather, it is that, " modern medicine and improved sanitation have sharply reduced infant, maternal and childhood mortality" (Samaras 2012, p. 248). A direct association study by He and colleagues (He et al, 2014) reports that shorter adult height is associated with greater longevity in both Japanese and American men.Moreover, this association seems to be mediated by a single nucleotide polymorphism of the G allele of the FOXO3 SNP (Willcox et al, 2008) that may also directly reduce growth in height. Evidence for a similar height-longevity association for women is not known, but we note that Japanese women are, on average, one of the longest lived populations but not one of the tallest -they rank 90 th in the NCDRisC height database.…”

Height and blood chemistry in adults with a history of developmental arsenic poisoning from contaminated milk powder

“…Although a small part of this substantial difference could perhaps be attributable to body posture, the standardized assessment of height in standing position suggests that the observed difference is real. Height may be inversely associated with longevity (He et al 2014), but a differential mortality before age 60 years would be unlikely to generate a difference in height as large as the one observed. A previous study from this mass arsenic poisoning already reported lower height among exposed victims at adolescence, although details were not provided (Uehata et al 1977).…”

Health Risks of Higher Birth Weight, Rapid Growth, Early Maturation and Taller Height

“…About 25 distinct biological factors have been identified (11,13,14,16,19) that support the benefits of smaller human body size in terms of health and longevity. For example, when compared to taller people of the same body proportions, shorter people have lower blood pressure, lower left ventricular mass, lower DNA damage, lower C-reactive protein, and lower insulin and insulin like growth factor-1.…”

“…In 2014, a large study (16) tracked about 8000 elderly male Japanese Hawaiians for over 40 years. The researchers found that shorter men lived longer, They also had lower insulin secretion, which is related to greater longevity (11).…”