Abstract
Advances in public health have nearly doubled life expectancy over the last century, but this demographic shift has also changed the landscape of human illness. Today, chronic and age-dependent diseases dominate the leading causes of morbidity and mortality worldwide. Targeting the underlying molecular, genetic and cell biological drivers of the aging process itself appears to be an increasingly viable strategy for developing therapeutics against these diseases of aging. Towards this end, one of the most exciting developments in cell biology over the last decade is the explosion of research into organelle contact sites and related mechanisms of inter-organelle communication. Identification of the molecular mediators of inter-organelle tethering and signaling is now allowing the field to investigate the consequences of aberrant organelle interactions, which frequently seem to correlate with age-onset pathophysiology. This review introduces the major cellular roles for inter-organelle interactions, including the regulation of organelle morphology, the transfer of ions, lipids and other metabolites, and the formation of hubs for nutrient and stress signaling. We explore how these interactions are disrupted in aging and present findings that modulation of inter-organelle communication is a promising avenue for promoting longevity. Through this review, we propose that the maintenance of inter-organelle interactions is a pillar of healthy aging. Learning how to target the cellular mechanisms for sensing and controlling inter-organelle communication is a key next hurdle for geroscience.