Degenerative protein modifications in the aging vasculature and central nervous system: A problem shared is not always halved.

ABSTRACT

Aging influences the pathogenesis and progression of several major diseases affecting both the cardiovascular system (CVS) and central nervous system (CNS). Defining the common molecular features that underpin these disorders in these crucial body systems will likely lead to increased quality of life and improved 'health-span' in the global aging population. Degenerative protein modifications (DPMs) have been strongly implicated in the molecular pathogenesis of several age-related diseases affecting the CVS and CNS, including atherosclerosis, heart disease, dementia syndromes, and stroke. However, these isolated findings have yet to be integrated into a wider framework, which considers the possibility that, despite their distinct features, CVS and CNS disorders may in fact be closely related phenomena. In this work, we review the current literature describing molecular roles of the major age-associated DPMs thought to significantly impact on human health, including carbamylation, citrullination and deamidation. In particular, we focus on data indicating that specific DPMs are shared between multiple age-related diseases in both CVS and CNS settings. By contextualizing these data, we aim to assist future studies in defining the universal mechanisms that underpin both vascular and neurological manifestations of age-related protein degeneration.