A pathological convergence theory for non‐communicable diseases

Abstract

The current paradigm considers the study of non‐communicable diseases (NCDs), which are the main causes of mortality, as individual disorders. Nevertheless, this conception is being solidly challenged by numerous remarkable studies. The clear fact that the mortality, by virtually all NCDs, tends to cluster at old ages (with the exception of congenital malformations and certain types of cancer, among a few others); makes us intuitive to assume that the common convergence mechanism that exponentially increases mortality by almost all NCDs in older ages is cell aging. Moreover, when we study NCDs, we are not analyzing which disorders cause the mortality of the populations, rather that which disorders kill us before others do, because the aging of the individuals causes inevitably their death by one cause or another. This is not a defeatist perspective, but a challenging and efficient one. These intuitive assumptions have been supported by studies from the pathophysiologic, epidemiologic, and genetic fields, leading to the affirmation that, as NCDs share genetic and pathophysiological mechanisms (derived from mostly the same risk factors), they should no longer be considered independently. Those studies should make us reconsider our current conceptions of studying NCDs as individual disorders, and to hypothesize about a paradigm that would consider most NCDs (cancer, neurological pathologies, cardiovascular diseases, type II diabetes mellitus, chronic respiratory diseases, osteoarthritis, and osteoporosis, among others) different manifestations of the same process: the cell aging.

Unveiling the double-edged sword: SOD1 trimers possess tissue-selective toxicity and bind septin-7 in motor neuron-like cells

“…Disrupting this binding interaction may offer a potential mechanism to mitigate neuronal death, given the known toxicity of SOD1 trimers. Discontinuity between the complex molecular etiology and phenotypic presentation of in ALS results begs the question whether there is a singular pathway leading to motor neuron death (convergence [89][90][91] ) or the result of distinct and even independent genetic, epigenetic, and environmental pathways (divergence [92][93][94] ). Our study expands upon prior research on ALS pathophysiology, revealing evidence for a convergence phenomenon centered around SOD1 trimers.…”