1 CUMULATIVE INDEX OF HEALTH DISORDERS AND LONGEVITY

We describe the accumulation of aging-associated health disorders by a cumulative measure known as a frailty index (FI) and evaluate the FIs ability to differentiate longand short-life phenotypes as well as the FIs connection to aging-associated processes in the elderly analyzing the National Long Term Care Survey data. We show that males and females died before age 75 and those who lived long and died at age 85+ exhibit remarkably similar FI frequency patterns despite the ten-year age difference between age profiles in these samples. Long life is consistently characterized in longitudinal analyses by lower levels of the FIs. FI dynamics are found to be strongly sex-sensitive. The FI appears to be a sensitive age-independent indicator of sex-specific physiological decline in aging individuals and sex-specific discriminator of survival chances. The FI is a promising characteristic suitable for improving sex-sensitive forecasts of risks of adverse health outcomes in the elderly. INTRODUCTION Experimental studies indicate that for many diseases incidence rates increase among adult and old individuals and then decline among the oldest old [1,2]. The forces shaping such age patterns leave the potential for a certain portion of survivors to escape major chronic diseases [24]. The total mortality rate, however, continues to increase to those ages. The recently developed concept of frailty appears to be helpful in addressing such a paradox, since frailty is consistently associated with pure health and death [5-8] and is a state of an organism with non-specific vulnerability to stressors [9]. Frailty appears to be a result of decreasing physiological reserves and deregulation of multiple physiologic systems. However, despite agreement on the physiological origin of frailty, its operational definition remains controversial [10]. One approach to operationalize frailty is through multiple physical indicators, e.g., declined grip strength, reduction of lean bodyweight, slowing mobility, poor endurance [5,11]. These factors (apart from a multitude of physiological indicators, see, e.g., [12]) were also considered as predictors of mortality both as individual indicators [13,14] and composite indices [7,9]. Another approach for assessing frailty is to track health and well-being changes in aging individuals [15]. Unlike more specific approaches [5,11], this approach defines frailty more broadly [16], assuming that more frail individuals will experience more health problems than those who are less frail [17]. An advantage of the FI concept is that it allows one to use conventional data collected in typical population-based surveys. The frailty state can be described by a cumulative index of health/well-being deficiencies that is assessable for each individual as the fraction of deficits among a list of items that measure health/well-being (called a frailty index, FI). According to this systemic approach, the frailty state appears to be characterized not by the substance of specific traits used to define the FI but by their aggregate (or systemic) ability to describe the decline in physiological performance in an organism – and, thus, to characterize its overall function [17]. The validity of such a conceptualization of frailty has been examined in a number of