Body mass index relates weight to height differently in women and older adults: serial cross-sectional surveys in England (1992-2011).

BACKGROUND: Body mass index (BMI) tends to be higher among shorter adults, especially women. The dependence of BMI-height correlation on age and calendar time may inform us about temporal determinants of BMI. METHODS: Series of cross-sectional surveys: Health Survey for England, 1992-2011. We study the Benn Index, which is the coefficient in a regression of log(weight) on log(height). This is adjusted for age, gender and calendar time, allowing for non-linear terms and interactions. RESULTS: By height quartile, mean BMI decreased with increasing height, more so in women than in men (P < 0.001). The decrease in mean BMI in the tallest compared with the shortest height quartile was 0.77 in men (95% CI 0.69, 0.86) and 1.98 in women (95% CI 1.89, 2.08). Regression analysis of log(weight) on log(height) revealed that the inverse association between BMI and height was more pronounced in older adults and stronger in women than in men, with little change over calendar time. CONCLUSIONS: Unlike early childhood, where taller children tend to have higher BMI, adults, especially women and older people, show an inverse BMI-height association. BMI is a heterogeneous measure of weight-for-height; height may be an important and complex determinant of BMI trajectory over the life course.

Proinflammatory genotype is associated with the frailty phenotype in the English Longitudinal Study of Ageing.

BACKGROUND: Frailty is a state of increased vulnerability to poor resolution of homeostasis after a stressor event, which increases the risk of adverse outcomes including falls, disability and death. The underlying pathophysiological pathways of frailty are not known but the hypothalamic-pituitary-adrenal axis and heightened chronic systemic inflammation appear to be major contributors. METHODS: We used the English Longitudinal Study of Ageing dataset of 3160 individuals over the age of 50 and assessed their frailty status according to the Fried-criteria. We selected single nucleotide polymorphisms in genes involved in the steroid hormone or inflammatory pathways and performed linear association analysis using age and sex as covariates. To support the biological plausibility of any genetic associations, we selected biomarker levels for further analyses to act as potential endophenotypes of our chosen genetic loci. RESULTS: The strongest association with frailty was observed in the Tumor Necrosis Factor (TNF) (rs1800629, P = 0.001198, ß = 0.0894) and the Protein Tyrosine Phosphatase, Receptor type, J (PTPRJ) (rs1566729, P = 0.001372, ß = 0.09397) genes. Rs1800629 was significantly associated with decreased levels of high-density lipoprotein (HDL) (P = 0.00949) and cholesterol levels (P = 0.00315), whereas rs1566729 was associated with increased levels of HDL (P = 0.01943). After correcting for multiple testing none of the associations remained significant. CONCLUSIONS: We provide potential evidence for the involvement of a multifunctional proinflammatory cytokine gene (TNF) in the frailty phenotype. The implication of this gene is further supported by association with the endophenotype biomarker results.

Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty.

Global ageing poses a substantial economic burden on health and social care costs. Enabling a greater proportion of older people to stay healthy for longer is key to the future sustainability of health, social and economic policy. Frailty and associated decrease in resilience plays a central role in poor health in later life. In this study, we present a population level assessment of the metabolic phenotype associated with frailty. Analysis of serum from 1191 older individuals (aged between 56 and 84 years old) and subsequent longitudinal validation (on 786 subjects) was carried out using liquid and gas chromatography-mass spectrometry metabolomics and stratified across a frailty index designed to quantitatively summarize vulnerability. Through multivariate regression and network modelling and mROC modeling we identified 12 significant metabolites (including three tocotrienols and six carnitines) that differentiate frail and non-frail phenotypes. Our study provides evidence that the dysregulation of carnitine shuttle and vitamin E pathways play a role in the risk of frailty.

Frailty Index associates with GRIN2B in two representative samples from the United States and the United Kingdom.

The concept of frailty has been used in the clinical and research field for more than two decades. It is usually described as a clinical state of heightened vulnerability to poor resolution of homeostasis after a stressor event, which thereby increases the risk of adverse outcomes, including falls, delirium, disability and mortality. Here we report the results of the first genome-wide association scan and comparative gene ontology analyses where we aimed to identify genes and pathways associated with the deficit model of frailty. We used a discovery-replication design with two independent, nationally representative samples of older adults. The square-root transformed Frailty Index (FI) was the outcome variable, and age and sex were included as covariates. We report one hit exceeding genome-wide significance: the rs6765037 A allele was significantly associated with a decrease in the square-root transformed FI score in the Discovery sample (beta = -0.01958, p = 2.14E-08), without confirmation in the Replication sample. We also report a nominal replication: the rs7134291 A allele was significantly associated with a decrease in the square-root transformed FI score (Discovery sample: beta = -0.01021, p = 1.85E-06, Replication sample: beta = -0.005013, p = 0.03433). These hits represent the KBTBD12 and the GRIN2B genes, respectively. Comparative gene ontology analysis identified the pathways 'Neuropathic pain signalling in dorsal horn neurons' and the 'GPCR-Mediated Nutrient Sensing in Enteroendocrine Cells', exceeding the p = 0.01 significance in both samples, although this result does not survive correction for multiple testing. Considering the crucial role of GRIN2B in brain development, synaptic plasticity and cognition, this gene appears to be a potential candidate to play a role in frailty. In conclusion, we conducted genome-wide association scan and pathway analyses and have identified genes and pathways with potential roles in frailty. However, frailty is a complex condition. Therefore, further research is required to confirm our results and more thoroughly identify relevant biological mechanisms.