Browsing by Author "Kulminski, A"

Now showing 1 - 9 of 9

Open Access
Age-Associated Disorders As A Proxy Measure Of Biological Age: Findings From the NLTCS Data
(2017-06-07) Kulminski, A; Yashin, A; Ukraintseva, S; Akushevich, I; Arbeev, K; Land, K; Manton, K
Background: The relative contribution of different aging-associated processes to the age phenotype may differ among individuals, creating variability in aging manifestations among age-peers. Capturing this variability can significantly advance understanding the aging and mortality. An index of age-associated health disorders (deficits), called a "frailty index" (FI), appears to be a promising characteristic of such processes. In this study we address the connections of the FI with age focusing on disabled individuals who might be at excessive risk of frailty. Methods: The National Long Term Care Survey (NLTCS) assessed health and functioning of the U.S. elderly in 1982, 1984, 1989, 1994, and 1999. Detailed information for our sample was assessed from about 26,700 interviews. The individual FI is defined as a proportion of deficits for a given person. We perform cross-sectional empirical analysis of the FI age-patterns. Results: FI in the NLTCS exhibits accelerated (quadratic) increase with age. Deficits might accumulate faster among the elderly who, at younger ages, had a low mean FI ("healthy" group) than a high FI ("disabled" group). Age-patterns for "healthy" and "disabled" groups converge at advanced ages. The rate of deficit accumulation is sex-sensitive. Convergence of the (sex-specific) FI for "healthy" and "disabled" groups in later ages determines biological age limits, associated with given levels of health-maintenance in the society, which correspond to 109.4 years for females and 92.5 years for males. Conclusions: The FI can be employed as a measure of biological age and population heterogeneity for modeling aging processes and mortality in elderly individuals.
Open Access
Frailty Index as a Major Indicator of Aging Processes and Mortality in Elderly: Results From Analyses of the National Long Term Care Survey Data
(2017-06-07) Kulminski, A; Yashin, A; Akushevich, I; Ukraintseva, S; Land, K; Arbeev, K; Manton, K
To better understand mortality change with age capturing the variability in individuals' rates of aging, we performed comprehensive analysis of statistical properties of a cumulative index of age-associated disorders (deficits), called a "frailty index" (FI). This index is calculated as the proportion of the health deficits in an individual. It is found, first, that frequency, time-to-death, mortality-rate, and relative-risk-of-death exhibit remarkably similar FI- and age- patterns. Second, the FI, on the one hand, and mortality rate and relative risk, on the other hand, also exhibit similar age patterns with accelerated increase up to oldest-old ages and with subsequent deceleration and even decline. Third, distribution of the FI with time-to-death is sharper than that of age with time-to-death. These and related findings support the conclusion that the FI can describe aging processes and population heterogeneity. We also discuss the ability of the FI to capture physiological processes underlying aging both on individual and population levels.
Open Access
Joint analysis of health histories, physiological state, and survival
(Mathematical Population Studies, 2011-12-01) Yashin, AI; Akushevich, I; Arbeev, KG; Kulminski, A; Ukraintseva, S
Data on individual health histories, age trajectories of physiological or biological variables, and mortality allow for the study of the joint evolution of health and physiological states and their effects on mortality. Individual health and physiological trajectories are described using a stochastic process with two mutuallydependent continuous and jumping components. The parameters of this process and mortality rate are identified from the data in which the continuous component is measured in discrete times, and transitions of jumping process are observed. © Taylor & Francis Group, LLC.
Open Access
Modeling longitudinal data on health aging and life span
(Physics of Life Reviews, 2012-06-01) Yashin, AI; Arbeev, KG; Akushevich, I; Kulminski, A; Ukraintseva, SV; Stallard, E; Land, KC
We address comments from the three discussants of our paper, paying particular attention to the properties of our model likely to be of interest in new applications to complex dynamic systems. © 2012 Elsevier B.V.
Open Access
Patterns of Aging-Related changes on the way to 100: An Approach to studying aging, mortality, and longevity from longitudinal data
(North American Actuarial Journal, 2012-12-01) Yashin, AI; Arbeev, KG; Ukraintseva, SV; Akushevich, I; Kulminski, A
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.
Open Access
Resistance to stresses and reliability of biological systems: Insights for genetic studies of human aging, health, and longevity
(Proceedings - 2nd International Symposium on Stochastic Models in Reliability Engineering, Life Science, and Operations Management, SMRLO 2016, 2016-03-11) Yashin, AI; Arbeev, KG; Arbeeva, LS; Wu, D; Akushevich, I; Kulminski, A; Kovtun, M; Zhbannikov, I; Ukraintseva, SV
© 2016 IEEE.Connection between stress resistance and longevity in biological organisms is widely discussed and confirmed experimentally. Much less is known about the roles of genetic and non-genetic factors in regulation of such connection. Earlier studies emphasized that mechanism that realizes such connection involves interplay between processes of individual aging and external challenges. As a result of such interplay the parameters of the Gompertz mortality curve are negatively correlated. Such correlation has been also observed in the process of survival improvement in developed part of the world during the first part of the last century. The mortality decline was mainly due to favorable changes in external and living conditions as well as progress in health care. Surprisingly, similar pattern of survival changes is observed in the groups of individuals ranked with respect to the number of «longevity» alleles carried by individuals. We showed that this phenomenon can be interpreted as an increase in resistance to stresses and showed that similar effect is observed in reliability of technical systems when redundancy of their components increases. The availability of longitudinal data for genotyped individuals opens unique opportunity to address more sophisticated questions about roles of genetic and non-genetic factors in connection between aging, stress resistance and longevity in humans. For this purpose the dynamic model of human mortality and aging is used. We show how such model can be used in genetic analyses of fundamental processes of interaction between genetic and non-genetic factors to influence human longevity.
Open Access
The quadratic hazard model for analyzing longitudinal data on aging, health, and the life span.
(Phys Life Rev, 2012-06) Yashin, AI; Arbeev, KG; Akushevich, I; Kulminski, A; Ukraintseva, SV; Stallard, E; Land, KC
A better understanding of processes and mechanisms linking human aging with changes in health status and survival requires methods capable of analyzing new data that take into account knowledge about these processes accumulated in the field. In this paper, we describe an approach to analyses of longitudinal data based on the use of stochastic process models of human aging, health, and longevity which allows for incorporating state of the art advances in aging research into the model structure. In particular, the model incorporates the notions of resistance to stresses, adaptive capacity, and "optimal" (normal) physiological states. To capture the effects of exposure to persistent external disturbances, the notions of allostatic adaptation and allostatic load are introduced. These notions facilitate the description and explanation of deviations of individuals' physiological indices from their normal states, which increase the chances of disease development and death. The model provides a convenient conceptual framework for comprehensive systemic analyses of aging-related changes in humans using longitudinal data and linking these changes with genotyping profiles, morbidity, and mortality risks. The model is used for developing new statistical methods for analyzing longitudinal data on aging, health, and longevity.
Open Access
THE ROLE OF THE APOLIPOPROTEIN E4 ALLELE, CANCER, CVD AND NEURODEGENERATIVE DISORDERS IN HUMAN LIFESPAN
(GERONTOLOGIST, 2013-11) Kulminski, A; Culminskaya, I; Arbeev, KG; Arbeeva, L; Ukraintseva, SV; Yashin, AI
Open Access
TRADE-OFF IN THE EFFECT OF THE APOLIPOPROTEIN E POLYMORPHISM ON THE AGES AT ONSET OF CVD AND CANCER: THE ROLE OF AGE AND GENDER ACROSS GENERATIONS
(GERONTOLOGIST, 2012-11) Kulminski, A; Culminskaya, I; Arbeev, KG; Ukraintseva, SV; Arbeeva, L; Yashin, AI