In vivo medical imaging for assessing geroprotective interventions in humans

Abstract

There is a growing interest in developing drugs with a general geroprotective effect, aimed at slowing down aging processes in humans. Several candidate compounds have already demonstrated increased lifespan and reduced incidence of age-related disease in short-lived model organisms. The extended lifespan of humans makes it challenging to translate these findings, especially if mortality or onset of age-related morbidity are to be used as trial endpoints. To address this, we propose using a battery of medical imaging protocols that allows for in vivo assessments of multiple age-related pathological processes known to precede onset of age-related disease. These protocols, based on magnetic resonance imaging, positron emission-, computer-, and optical coherence-tomography, are already in use in drug development and are available at most modern hospitals. Here, we outline how an informed use of these techniques allows for detecting changes in the accumulation of age-related pathologies in a diverse set of physiological systems, such as cardiovascular, kidney and metabolic function, periodontal inflammation, retinal or neuro-degeneration, and bone or muscle density. With this in vivo imaging battery, it is possible to screen for efficacy of candidate geroprotective compounds in early phase clinical trials, within reasonable trial durations.