Age differences in allostatic load: an index of physiological dysregulation

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Abstract

This preliminary report examines variation in allostatic load by age for a large nationally representative population of the United States. It uses data on 13 indicators of physiologic dysregulation from a nationally representative sample of the US population 20 years of age and over. Allostatic load is remarkably constant in the older ages after increasing sharply in the years from 20 to 60. We hypothesize that this represents mortality selectivity of the population by physiological status.

Introduction

We are interested in examining age differences in a summary indicator of biological risk—allostatic load. Our analysis clarifies how physiological dysregulation varies by age in a national sample of the US population. As such it indicates how a population's physiological risk differs with age when characteristics of the population at birth may have changed as well as their past lifestyle and selective survival to a given age.

A number of studies have examined both age differences and age changes in a variety of indicators of physiological capacity or of physiological reserve (Lipsitz and Goldberger, 1992, Manton et al., 1995). These studies make clear that in many indicators of physiological state there is decline with age although there is great variability in the rate of change and its relationship to age.

This study investigates age differences in allostatic load, a summary indicator of physiological challenge that has been both developed theoretically and related to a variety of health outcomes in a number of recent studies (McEwen, 1998, McEwen and Stellar, 1993, Seeman et al., 1997, Sterling and Eyer, 1988). In the course of normal life experiences, challenge to various physiological systems is met with physiological responses appropriate to eliminating the threat posed by the challenge. Such bodily responses should occur within an optimal range. When the body has received significant challenge over many years, physiological systems may begin to operate outside this optimal range or may have difficulty returning to optimal ranges after challenge. Operation of physiological systems outside some optimal range is allostatic load.

Allostatic load could be regarded as a direct indicator of population frailty as it is indicative of the extent to which the body is at risk of adverse health outcomes because of physiologic dysregulation. Allostatic load has been linked to mortality as well as other adverse health outcomes such as cardiovascular disease and cognitive failure (Seeman et al., 2001). In this paper we are interested in the age pattern of increase in physiological frailty across the adult years, as represented by allostatic load. Of particular interest is whether there is any leveling off of physiological risk as the oldest ages are approached.

Allostatic load is an indicator of the physiological challenge currently being experienced by an organism with multiple complex systems which interact to produce health outcomes. If multiple systems are operating outside normal ranges, the likelihood that the body will experience adverse health consequences increases. In this way it corresponds to the idea of frailty or risk of mortality described by Kannisto when he said that deaths were the outcome of ‘little devils’ or potential causes of death that can either work together or individually to harm the organism (Kannisto, 1991). Other summary indicators of physiological status have been related to both mortality and specific causes of morbidity. For instance, Metabolic syndrome, a combination of cardiovascular and metabolic risk factors has been related to cardiovascular mortality (Lakka et al., 2002). And a summary index of cardiovascular risk has been developed by the Framingham group (Wilson et al., 1998).

Parameters included in earlier specifications of allostatic load have included profiles of physiologic activity across a range of regulatory systems including the hypothalmic pituitary axis, the sympathetic nervous system, the cardiovascular system, the metabolic system, renal function, lung function, and markers of inflammation (Seeman et al., 1997, Seeman et al., 2001). Values of allostatic load have been used to predict subsequent mortality and the onset of both cardiovascular conditions and cognitive decline. These analyses have been performed within an age-limited sample, the MacArthur Study of Successful Aging, ranging in age from 70 to 79 at the onset of the study. In addition allostatic load has been examined within a middle-aged sample (Singer and Ryff, 1999). The current study is the first to empirically examine allostatic load in a representative population sample, spanning the adult age range.

Section snippets

Materials and methods

NHANES data. Data for this study come from the third National Health and Nutrition Examination Survey (NHANES III). The survey and examination involved the collection of data over the 1988–94 period from about 18,000 persons 20 years of age or older in a nationally representative sample of the US noninstitutional population (National Center for Health Statistics, 1994). In order to address health issues relevant to older persons and minorities, these groups were oversampled. The NHANES study

Results

Age differences in risk factors. Since our interest is in how risk varies with age, we examine the age–sex distribution of allostatic load in Fig. 1. Physiological challenge as represented by allostatic load increases with age up through the 60s and then levels off so that the population has fairly similar levels of allostatic load during their 60s, 70s, 80s, and 90s. Ratios of one age group to the preceding show that the increase from one age group to the next is .4 or .5 in the first two

Discussion

While we are looking at a cross-section of the population by age, we are very cognizant of the fact that the population in each age group examined is the surviving population from the cohorts born years earlier. The selectivity of the population is greater as age increases. Using current mortality rates and the resulting cross-sectional life table indicates that about half of the population will die by age 80 and only about a third of those who reach 80 survive to age 90. For current 80 year

Acknowledgements

This paper was supported by grants from the US National Institute on Aging: NIA ROI-AG17055 and NIA P30-AG17265.

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