Patterns of Aging-Related Changes on the Way to 100

Abstract

The objective of this paper is to investigate dynamic properties of age trajectories of physiological indices and their effects on mortality risk and longevity using longitudinal data on more than 5,000 individuals collected in biennial examinations of the Framingham Heart Study (FHS) original cohort during about 50 subsequent years of follow-up. We first performed empirical analyses of the FHS longitudinal data. We evaluated average age trajectories of indices describing physiological states for different groups of individuals and established their connections with mortality risk. These indices include body mass index, diastolic blood pressure, pulse pressure, pulse rate, level of blood glucose, hematocrit, and serum cholesterol. To be able to investigate dynamic mechanisms responsible for changes in the aging human organisms using available longitudinal data, we further developed a stochastic process model of human mortality and aging, by including in it the notions of “physiological norms,” “allostatic adaptation and allostatic load,” “stress resistance,” and other characteristics associated with the internal process of aging and the effects of external disturbances. In this model, the persistent deviation of physiological indices from their normal values contributes to an increase in morbidity and mortality risks. We used the stochastic process model in the statistical analyses of longitudinal FHS data. We found that different indices have different average age patterns and different dynamic properties. We also found that age trajectories of long-lived individuals differ from those of the shorter-lived members of the FHS original cohort for both sexes. Using methods of statistical modeling, we evaluated “normal” age trajectories of physiological indices and the dynamic effects of allostatic adaptation. The model allows for evaluating average patterns of aging-related decline in stress resistance. This effect is captured by the narrowing of the U-shaped mortality risk (considered a function of physiological state) with age. We showed that individual indices and their rates of change with age, as well as other measures of individual variability, manifested during the life course are important contributors to mortality risks. The advantages and limitations of the approach are discussed.     

How Genes Modulate Patterns of Aging-Related Changes on the Way to 100: Biodemographic Models and Methods in Genetic Analyses of Longitudinal Data

In this article we clarify mechanisms of genetic regulation of human aging and longevity traits. The objective of this article is to address the issues in previous research of not reaching a genome-wide level of statistical significance and lack of replication in the studies of independent populations. We performed GWAS of human life span using different subsets of data from the original Framingham Heart Study cohort corresponding to different quality control procedures, and we used one subset of selected genetic variants for further analyses. We used a simulation study to show that this approach to combining data improves the quality of GWAS with FHS longitudinal data to compare average age trajectories of physiological variables in carriers and noncarriers of selected genetic variants. We used a stochastic process model of human mortality and aging to investigate genetic influence on hidden biomarkers of aging and on dynamic interaction between aging and longevity. We investigated properties of genes related to selected variants and their roles in signaling and metabolic pathways and showed that the use of different quality control procedures results in different sets of genetic variants associated with life span. We selected 24 genetic variants negatively associated with life span and showed that the joint analyses of genetic data at the time of biospecimen collection and follow-up data substantially improved significance of associations of 24 selected SNPs with life span. We also showed that aging-related changes in physiological variables and in hidden biomarkers of aging differ for the groups of carriers and noncarriers of selected variants. The results of these analyses demonstrated benefits of using biodemographic models and methods in genetic association studies of these traits. Our findings showed that the absence of a large number of genetic variants with deleterious effects may make substantial contribution to exceptional longevity. These effects are dynamically mediated by a number of physiological variables and hidden biomarkers of aging. The results of these research demonstrated benefits of using integrative statistical models of mortality risks in genetic studies of human aging and longevity.     

Public evaluation of landscape content and change: Several examples from Europe

This paper considers rural land use by analysing stakeholder values and perceptions concerning various landscape components. The purpose is to show that landscape content and land cover interactions with societal connections should be a base for land use development. The practical goal is to deliberate research tools to quantify public opinions and attitudes, which could form bases for developing of decision support tools. The main research objectives are: (1) to assess existing opinions concerning land use changes and provide a clearer insight into public attitudes to the role of woodlands for an integrated development of the countryside; (2) to place ecological and socio-economic values on inanimate natural components of landscapes; and (3) to assess values and preferences held by land use policy and management experts regarding multiple landscape components and features to assist in decision-making. Through the different levels of importance (values) accorded by the respondents to the integration of nature components in rural landscapes public priorities were identified. The paper develops an understanding of why certain aspects of land use changes are unfavourably viewed by some people and favourably received by others. It suggests some innovative perspectives on the areas of consensus and conflict between people, providing initial information for the selection and evaluation of land use management decisions.     

Bayesian Modeling of Shock Lapse Rates Provides New Evidence for Emergency Fund Hypothesis

This article considers the problem of estimating shock lapse rates in term life products. Four models are estimated using Bayesian Multiple-Block Gibbs sampling. Goodness-of-fit was compared using weighted average lapse rate fitted error. A simulated data setting was employed to validate the algorithm. Among the methodological contributions to the literature we introduce Bayesian estimation for the lapse rate parameters permitting the identification of parameter distributions as opposed to point estimates. Also we introduce a flexible panel data model accommodating both mixed effects and cross-effects between explanatory variables. The data are weighted in the likelihood function according to their relevance as measured by policy counts. Finally, we utilize a large proprietary dataset of U.S. postlevel premium period term policies that enables superior inference over the parameter estimates. Building on the above improvements and recent data covering the 2008 crisis, we find strong evidence in favor of the Emergency Fund Hypothesis as a driver of shock lapses.