Causal Effects of Environmental Exposures and Biological Traits on the Difference between Phenotypic and Chronological Ages

Aging is a physiological process associated with numerous cardiovascular, degenerative and neurological conditions. The current demographic changes in the world, characterized by an increasing average age especially in Europe and North America, are causing an increment in the prevalence of such conditions, leading to a public health problem as more resources are required to manage treatments. Recent research has defined a new score named Phenotypic Age, i.e. an adjusted age that takes into account the current health status considering a series of biomarkers, that can be useful to provide a more precise estimation of the probability of developing aging-related conditions. Prevention of such conditions can be performed more efficiently by studying the mechanisms that lead to an increased phenotypic age rather than attempting to treat a patient that has already a high health risk. In this work, we combine pairwise association techniques and mediation analysis to define a strategy to investigate the inner causal mechanisms that lead from specific environmental exposures to an increasing gap between phenotypic and chronological age, considering the influence of biological variables. Four environmental exposures and 11 biological traits have been identified in the NHANES dataset, and each trait has been tested as a mediation variable for each exposure. Almost all mediations reported significant indirect effects with specific results that provide new insights into the causal mechanisms that lead to a deranged aging rate.