Time for the systems-level integration of aging: Resilience enhancing strategies to prevent Alzheimer’s disease

Publication date: Available online 25 July 2019Source: Progress in NeurobiologyAuthor(s): Harald Hampel, Simone Lista, Christian Neri, Andrea Vergallo, for the Alzheimer Precision Medicine Initiative (APMI)AbstractSystems biology and systems neurophysiology generate comprehensive mechanistic models of the spatial-temporal evolution of body system networks and their interplay during the dimensional spectrum from physiological to pathophysiological conditions.Alzheimer’s disease (AD)-related pathophysiological alterations converge with overexpressed age-related functional decline, i.e. aging, which is induced by genetic- and stochastic time-dependent events.Accumulation of cellular senescence has a casual role in aging-related disease and senolytics drugs have already shown encouraging results for counteracting senescence detrimental effect.However, the non-linear complex nature of AD pathophysiology calls for a systems-level integration of aging dynamics, from molecules until large-scale networks.We need a holistic systems-wide comprehensive model of aging which is constituted by a non-linear spatial-temporal weakening of adaptive responses resulting in the activation of compensatory mechanisms that ensure biological robustness, resilience, and finally homeodynamics.After exceeding the threshold of compensated (resilient) aging, a cascade of decompensatory events occurs, ultimately triggering irreversible systems failure that at some advanced stage reflect widespread “path...
Source: Progress in Neurobiology - Category: Neuroscience Source Type: research