A systems analysis of age-related changes in some cardiac aging traits.

Aging process or senescence affects the expression of a wide range of phenotypic traits throughout the life span of organisms. These traits often show modular, synergistic, and even antagonistic relationships, and are also influenced by genomic, developmental, physiological and environmental factors. The cardiovascular system (CVS) in humans represents a major modular system in which the relationships among physiological, anatomical and morphological traits undergo continuous remodeling throughout the life span of an individual. Here we extend the concept of developmental plasticity in order to study the relationships among 14 traits measured on 3,412 individuals from the Framingham Heart Study cohort, relative to age and gender, using exploratory structural equation modeling-a form of systems analysis. Our results reveal differing patterns of association among cardiac traits in younger and older persons in both sexes, indicating that physiological and developmental factors may be channeled differentially in relation to age and gender during the remodeling process. We suggest that systems approaches are necessary in order to understand the coordinated functional relationships among traits of the CVS over the life course of individuals.

Inborn errors of metabolism diagnosed in sudden death cases by acylcarnitine analysis of postmortem bile.

Fatty acid oxidation (FAO) disorders represent a frequently misdiagnosed group of inborn errors of metabolism. Some patients die at the first episode of fasting intolerance and, if appropriate investigations are not undertaken, often meet the criteria of sudden infant death syndrome (SIDS). To expand existing protocols for the postmortem diagnosis of FAO and other metabolic disorders, we tested the hypothesis that analysis for acylcarnitine in bile, a specimen readily available at autopsy, may be utilized for diagnostic purposes. Using electrospray/tandem mass spectrometry, we analyzed for acylcarnitine postmortem bile specimens from two infants with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, one infant with glutaryl-CoA dehydrogenase deficiency, and 17 uninformative SIDS cases as controls. The affected cases, and none of the controls, showed marked accumulation of C10-C18 acylcarnitines or glutarylcarnitine (acyl/free carnitine ratio: 5.2, 2.7, and 1.9, respectively; controls 0.2 +/- 0.1). In one patient, all other diagnostic methods were uninformative, suggesting that bile acylcarnitine profiling could lead to identification of previously overlooked cases.