Age-related physiological changes in humans are linearly associated with age. Naturally, linear combinations of physiological measures trained to estimate chronological age have recently emerged as a practical way to quantify aging in the form of biological age. In this work, we used one-week long physical activity records from a 2003–2006 National Health and Nutrition Examination Survey (NHANES) to compare three increasingly accurate biological age models: the unsupervised Principal Components Analysis (PCA) score, a multivariate linear regression, and a state-of-the-art deep convolutional neural network (CNN). We found that the supervised approaches produce better chronological age estimations at the expense of a loss of the association between the aging acceleration and all-cause mortality. Consequently, we turned to the NHANES death register directly and introduced a novel way to train parametric proportional hazards models suitable for out-of-the-box implementation with any modern machine learning software. As a demonstration, we produced a separate deep CNN for mortality risks prediction that outperformed any of the biological age or a simple linear proportional hazards model. Altogether, our findings demonstrate the emerging potential of combined wearable sensors and deep learning technologies for applications involving continuous health risk monitoring and real-time feedback to patients and care providers.
We performed a systematic evaluation of the relationships between locomotor activity and signatures of frailty, morbidity, and mortality risks using physical activity records from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) and UK BioBank (UKB). We proposed a statistical description of the locomotor activity tracks and transformed the provided time series into vectors representing physiological states for each participant. The Principal Component Analysis of the transformed data revealed a winding trajectory with distinct segments corresponding to subsequent human development stages. The extended linear phase starts from 35−40 years old and is associated with the exponential increase of mortality risks according to the Gompertz mortality law. We characterized the distance traveled along the aging trajectory as a natural measure of biological age and demonstrated its significant association with frailty and hazardous lifestyles, along with the remaining lifespan and healthspan of an individual. The biological age explained most of the variance of the log-hazard ratio that was obtained by fitting directly to mortality and the incidence of chronic diseases. Our findings highlight the intimate relationship between the supervised and unsupervised signatures of the biological age and frailty, a consequence of the low intrinsic dimensionality of the aging dynamics.
Since chronological age is not a complete and accurate indicator of organism aging, the concept of biological age has emerged as a well-accepted way to quantify the aging process in humans and laboratory animals. In this study, we performed a systematic statistical evaluation of the relationships between locomotor activity and biological age, mortality risk, and frailty using human physical activity records from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) and UK BioBank (UKBB) databases. These records are from subjects ranging from 5 to 85 years old and include 7-day long continuous tracks of activity provided by wearable monitors as well as data for a comprehensive set of clinical parameters, lifestyle information and death records, thus enabling quantitative assessment of frailty and mortality. We proposed a statistical description of the locomotor activity tracks and transformed the provided time series into vectors representing individual physiological states for each participant. Using this data, we performed an unsupervised multivariate analysis and observed development and aging as a continuous trajectory consisting of distinct phases, each corresponding to subsequent human life stages. Therefore, we suggest the distance measured along this trajectory as a definition of the biological age. Consistent with the Gompertz law, mortality, estimated with the help of a proportional hazard model, was found to be an exponential function of biological age as quantified herein. However, we observed that the significant contribution of clinical frailty to mortality risk can be independent of biological age. We used the biological age and mortality models to show that some lifestyle variables, such as smoking, produce a reversible increase in all-cause mortality without a significant effect on biological age. In contrast, medical conditions, such as type 2 diabetes mellitus (T2DM) or hypertension, are associated with significant aging acceleration and a corresponding increase in mortality as well. The results of this work demonstrate that significant information relevant to aging can be extracted from human locomotor activity data and highlight the opportunity provided by explosive deployment of wearable sensors to use such information to encourage lifestyle modifications and clinical development of therapeutic interventions against the aging process.
Aging-related physiological changes are systemic and, at least in humans, are linearly associated with age. Therefore, linear combinations of physiological measures trained to estimate chronological age have recently emerged as a practical way to quantify aging in the form of biological age. Aging acceleration, defined as the difference between the predicted and chronological age was found to be elevated in patients with major diseases and is predictive of mortality. In this work, we compare three increasingly accurate biological age models: metrics derived from unsupervised Principal Components Analysis (PCA), alongside two supervised biological age models; a multivariate linear regression and a state-of-the-art deep convolution neural network (CNN). All predictions were made using one-week long locomotor activity records from a 2003-2006 National Health and Nutrition Examination Survey (NHANES) dataset. We found that application of the supervised approaches improves the accuracy of the chronological age estimation at the expense of a loss of the association between the aging acceleration predicted by the model and all-cause mortality. Instead, we turned to the NHANES death register and introduced a novel way to train parametric proportional hazards models in a form suitable for out-of-the-box implementation with any modern machine learning software. Finally, we characterized a proof-of-concept example, a separate deep CNN trained to predict mortality risks that outperformed any of the biological age or simple linear proportional hazards models. Our findings demonstrate the emerging potential of combined wearable sensors and deep learning technologies for applications involving continuous health risk monitoring and real-time feedback to patients and care providers.
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