O167 Pharmacological Sirt1 Activation In Apoe-/- Mice Provides Atheroprotection By Reducing Hepatic Pcsk9 Secretion And Enhancing Ldl-R Expression

The challenges posed by maintaining the proteome in a dynamic and functional state while mitigating the dangers of protein misfolding have necessitated the evolution of a conserved set of machineries to control protein homeostasis, referred to as the proteostasis network. The size and complexity of an organism's proteostasis network positively correlate with the life span and health span. Its dysregulation is widely accepted as a primary driver of cellular and organismal aging. Furthermore, a broad range of age-associated pathologies, including neurodegeneration, cardiovascular disease, and cancer, display characteristic rewiring of the proteostatic circuitry. In this chapter, we summarize the current state of research on how the proteostasis network is dysregulated during normal aging, mechanisms proposed for how this dysregulation drives aging-related frailty and disease, and potential interventions that hold promise for restoring proteostasis balance to maintain lifelong health.